www.emucbarcelona2012.org
4th EMUC, Barcelona, November 2012
Embracing Excellence
in Prostate, Bladder
and Kidney Cancer
16-18 November 2012
Barcelona, Spain
Programme/
Abstract book
These are the challenges we have set ourselves because Changing tomorrow is more than just
words – it is what we must do to give cancer patients real hope of a tomorrow worth looking
forward to.
www.astellas.eu
В© September 2012 Astellas Pharma Europe Ltd. CSC0461
ASTELLAS, Leading Light for Life, the Star logo, Changing tomorrow and the
Ribbon logos are trade marks of Astellas Pharma Inc. and/or its related entities.
Programme/Abstract book
Astellas has made a commitment to change
tomorrow – a commitment that we are bringing to the
field of oncology. We aim to create innovative treatments that will
genuinely improve the lives of cancer patients. To do this we are focusing
our R&D and partnership efforts into precision medicine that will create first-in-class
or best-in-class programmes. This has resulted in no fewer than 12 separate therapies under clinical
development into conditions including prostate cancer, other solid tumours like pancreatic cancer,
breast cancer and advanced renal cell carcinoma, as well as haematological malignancies.
4th European Multidisciplinary Meeting on Urological Cancers organised by:
Table of Contents
Welcome
4
Organisers
5
Sponsor Acknowledgement
6
General Information
9
Continuing Medical Education Accreditation
12
Scientific Programme
13
Friday, 16 November 19
Saturday, 17 November
21
Sunday, 18 November
24
Abstracts
27
Oral Presentations
29
Unmoderated Poster Presentations
47
Exhibition
167
Company and Product Description
169
About the Organisers
173
About EAU
175
About ESMO
177
About ESTRO
178
Indices
181
Abstract Authors
183
Abstracts sorted by Topic
192
Faculty List
194
3
Welcome to the 4th European Multidisciplinary
Meeting on Urological Cancers
The concept of multidisciplinary cooperation in the management of urological cancers is no longer a
novelty. It is being integrated into clinical practice by hospital departments and it is now openly discussed
on various strategic and scientific levels.
This trend is now well-established and yet only a few years ago, when we convened for the 1st EMUC in
2007, many of these developments were only starting to crystalise into a consistent approach. We believe
that the European Multidisciplinary Meeting on Urological Cancers has acted as a catalyst and contributed
to the further integration of the multidisciplinary approach in onco-urology.
Today, we are facing new challenges. The established multidisciplinary framework is branching out,
opening new doors and identifying new areas of cooperation. To match the intensity at which new
developments occur, the EMUC will now be organised annually. Your participation to the EMUC’s 4th
edition manifests the growing relevance of the multidisciplinary approach since this event is more than an
opportunity for professional development-- it is also a chance to engage with onco-urological science on
an entirely new level.
The 4th European Multidisciplinary Meeting on Urological Cancers brings together professionals from
three fields: urology, medical oncology and radiology. Our main objective will remain, as we will continue
to stimulate discussion and cooperation across disciplines and formulate optimal treatment strategies for
onco-urological patients. At the same time, we will be zooming in on translational and basic science as
well as technology, giving extra attention to some of the most forward-looking findings in the field.
The format of this meeting will feature state-of-the art lectures, practice-oriented case discussions and
exciting debates – generating top-class international multidisciplinary knowledge. At the same time,
there will be plenty of opportunity for the delegates to talk to the world’s leading experts and build
interdisciplinary networks.
See you in Barcelona!
Prof. Manfred Wirth
EAU Treasurer & Executive Member Communication
Prof. Karim Fizazi
ESMO Chair
Prof. Vincenzo Valentini
ESTRO President
4
Organisers
EMUC Organising Steering Committee
EAU ESMO ESTRO Manfred Wirth, Dresden (DE)
Karim Fizazi, Villejuif (FR)
Vincenzo Valentini, Rome (IT)
EMUC Scientific Committee
EAU EAU ESMO ESMO ESTRO ESTRO ESUR EORTC Genito Urinary Cancer Group Walter Artibani, Verona (IT)
Steven Joniau, Leuven (BE)
Johann De Bono, Sutton (GB)
Hans Joachim Schmoll, Halle (DE)
Alberto Bossi, Villejuif (FR)
David Dearnaley, Sutton (GB)
Gertraud Heinz-Peer, Vienna (AT)
Bertrand Tombal, Brussels (BE)
EMUC Congress Office
Congress Consultants B.V.
PO Box 30016
6803 AA Arnhem
The Netherlands
T +31 (0)26 389 1751
F +31 (0)26 389 1752
[email protected]
www.emucbarcelona2012.org
5
Sponsor Acknowledgement
The organisers respectfully acknowledge the following sponsors for providing unrestricted educational
grants and services to the 4th European Multidisciplinary Meeting on Urological Cancers “Embracing
Excellence in Prostate, Bladder and Kidney Cancer”.
Gold Sponsor
Silver Sponsor
Other Sponsors and Exhibitors
Accuray
Dendreon Corporation
Elekta
Wisepress medical bookshop
Floorplan
6
General
General Information
Continuing Medical Education Accreditation
(CME)
7
General
4th European
Multidisciplinary Meeting
on Urological Cancers
Embracing Excellence in treatment of
Prostate, Bladder and Kidney Cancer
Selected webcasts will be available shortly after the sessions
www.emucbarcelona2012.org
General
General Information
Abstracts and Posters
The abstracts are included in this book. Abstracts and posters are available on-line from 16 November
2012 on www.emucbarcelona2012.org.
Accessibility Congress Venue
The EMUC 2012 will take place at the Palau de Congressos de Catalunya which is easily accessible by
public transport. Congress delegates will receive a transportation pass which is valid on all public transport
within the city of Barcelona during the meeting.
Metro
Green Line (L3) to “Zona Universitaria” (2 minutes walking distance)
Address
Palau de Congressos de Catalunya
Av. Diagonal, 661-671
08028 Barcelona
Spain
T +34 (0)93 3644 400
F +34 (0)93 3644 401
www.pcongresos.com
www.hrjuancarlos.com
Barcelona Information
Information on Barcelona will be available at a special desk in the main entrance area of the congress
venue.
Certificate of Attendance
A Certificate of Attendance for the 4th European Multidisciplinary Meeting on Urological Cancers can be
printed online from Sunday, 18 November onwards on www.emucbarcelona2012.org. A barcode (indicated
on congress badge) is necessary to access the dedicated website.
Cloakroom/luggage
A cloakroom is located in the main entrance area and is at participants’ disposal during meeting hours.
Be sure to collect all personal belongings at the end of the day.
Congress Bag
Each delegate may collect a congress bag which includes a programme/abstract book.
Disclosure Links to Industry
It is requested that all faculty disclose to the audience any links with the industry related to the topic of
their lecture at the beginning of each presentation. A link can be: Being a member of the advisory board or
having a consulting agreement with a specific company.
Emergency Information
Emergency phone number for police, fire brigade and ambulance service is 112. In case of an emergency
in the congress venue contact the security or the organisation immediately. A First Aid unit is available on
level -1.
9
General
Exhibition
A technical exhibition will be held jointly with the meeting. See page 167 for more information on the
exhibiting companies and the company profiles.
Exhibition opening hours:
Friday, 16 November
09.00 - 16.00 hrs
Saturday, 17 November 09.00 - 16.00 hrs
Sunday, 18 November 09.00 - 13.00 hrs
First Aid
There will be a First Aid unit present on level -1. In case of an emergency contact a security guard or the
organisation immediately.
Insurance
The organisers do not accept responsibility for any personal damage. Participants are strongly
recommended to arrange their own personal insurance.
Language
All presentations during the meeting will be conducted in English. No translation will be provided.
Lost and Found
Found items should be returned to the registration desk. If you lose something, please report to this desk
for assistance.
Mobile phones
Mobile phones must be switched off during sessions.
Press
Journalists can obtain free registration to the meeting. All media operators must show their credentials
(press card dated 2011/2012 and original assignment letter).
Registration area
The registration area is located in the main entrance on level 0.
Opening hours
Wednesday, 14 November
Thursday, 15 November
Friday, 16 November
Saturday, 17 November
Sunday, 18 November
16.00 - 18.30hrs
07.00 - 19.00 hrs
07.00 - 17.15 hrs
07.30 - 17.15 hrs
07.30 - 14.30 hrs
Safety
All bags may be subject to inspection. Security is present for your safety. Please take all personal effects
with you when leaving the session rooms.
Scientific Posters
The scientific posters are on display from 16 to 18 November in the poster area in the exhibition hall. It has
been requested that one of the authors is present to answer questions during the following poster viewing
hours:
Members of the EMUC Scientific Committee will visit the poster area per topic to discuss the poster with
the presenter according to the following schedule.
10
General
Friday, 16 November
10.00-10.30 Topics: Prostate cancer P049 - P066
12.00-13.30 Topics: Prostate cancer P067 - P106
15.00-15.30 Topics: Prostate cancer P107 - P122
Saturday, 17 November 10.00-10.30 Topics: Kidney cancer P030 - P041
12.00-13.30 Topics: Bladder cancer P001 - P029
14.30-15.00 Topics: Kidney cancer,
Testicular and Penile P042 - P048 + P123 - P126
Sunday, 18 November 10.00-10.30 General poster viewing times for those who are interested
For those who presented their poster on Friday you are kindly invited to attend the scientific programme the
next day. We will announce the best poster at 10:00 hrs on Saturday 17 November in the main auditorium.
For those who presented their poster on Saturday you are kindly invited to attend the scientific programme
on Sunday. The best poster will be announced at 10:00 hrs on Sunday, 18 November in the main
auditorium.
Smoking Policy
Smoking is prohibited inside the congress venue.
Speaker Service Centre (SSC)
All presentations should be handed in at the Speaker Service Centre at least three hours prior to the start
of the session. Please follow the signage from the main entrance to the Speaker Service Centre.
Opening hours:
Wednesday, 14 November
16.00 - 18.30 hrs
Thursday, 15 November
07.00 - 16.45 hrs
Friday, 16 November
07.00 - 17.15 hrs
07.30 - 17.15 hrs
Saturday,17 November
07.30 - 14.15 hrs
Sunday, 18 November
Transportation
Delegates may collect a transportation pass in the registration area. The pass provides 10 journeys on the
metro, FGC (FGC run train lines similar to the metro around the city centre) buses, tram and RENFE trains all Zone 1 areas. The main city centre areas are all in Zone 1. The nearest metro stop “Zona Universitaria”
on the Green line (L3) is within 2 minutes’ walking distance of the congress venue.
Note: to use the transportation ticket you have to put the card in the machine and then pull it out completely
from the ticket validation machine – this will release the turnstile to allow you through.
Webcasts
All sessions during the 4th European Multidisciplinary Meeting on Urological Cancers in Barcelona will be
broadcasted via www.emucbarcelona2012.org (provided the speaker has given approval).
11
General
Continuing Medical Education Accreditation (CME)
The 4th European Multidisciplinary Meeting on Urological Cancers, Embracing Excellence in Prostate,
Bladder and Kidney Cancer, Barcelona, Spain, 16 - 18 November 2012 is accredited for 15 hours of
European CME credits in compliance with the UEMS/EACCME regulations: 1 hour = 1 European CME credit
with a maximum of 6 European CME credits per day.
The EBU works according to the quality standards of the European Accreditation Council for Continuing
Medical Education (EACCME).
Both the EBU and the EACCME are the institutions of the European Union of Medical Specialists (UEMS),
www.uems.net.
All CME events accredited by the EBU have the EACCME endorsement.
The EBU/EACCME CME Credits are recognised by National Accreditation Authorities.
Each medical specialist should claim only those hours of credit that he/she actually spent in the
educational activity.
All CME activities approved by the EBU/EACCME are valid for recognition by the American Medical
Association towards the Physician’s Recognition Award (PRA). To convert EACCME credit to AMA PRA
category 1 credit, contact the AMA.
12
Scientific Programme
Friday, 16 November
Saturday, 17 November
Scientific
Programme
Sunday, 18 November
13
Programme
Friday, 16 November 2012
This symposium will take place in the main auditorium
Symposium
CRPC: The future of therapy in your hands
12.30 - 12.35
Introduction
J. Bellmunt, Barcelona (ES) - Chair
12.35 - 12.50
CRPC: The rationale for AR-targeted therapies
J. Schalken, Nijmegen (NL)
12.50 - 13.05 New and emerging hormonal therapies in CRPC
J. Bellmunt, Barcelona (ES)
13.05 - 13.25 The changing face of CRPC management: Optimising patient care
B. Tombal, Brussels (BE)
13.25 - 13.30 Concluding remarks
J. Bellmunt, Barcelona (ES)
Programme
12.30 - 13.30 hrs Sponsored by ASTELLAS
15
Saturday, 17 November 2012
This symposium will take place in the main auditorium
Programme
Symposium
12.30 - 13.30 hrs Is there a need for a new TKI in advanced RCC?
12.30 - 12.35
Welcome and introduction
B. Escudier, Paris (FR)
12.35 - 12.50
Is there a need for another TKI for the first-line treatment of advanced RCC?
M. Schmidinger, Vienna (AT)
12.50 - 13.05
The future of RCC treatment: A new generation of TKIs?
T. Eisen, Cambridge (GB)
13.05 - 13.20
Case history: the physician and patient experience
C. Porta, Pavia (IT)
13.20 - 13.25
Summary
B. Escudier, Paris (FR)
13.25 - 13.30
Questions and answers
Sponsored by ASTELLAS
16
Saturday, 17 November 2012
This symposium will take place in the main auditorium
Symposium
CyberKnifeВ® System: The virtual scalpel to treat prostate
cancer patients
V. Khoo, London (GB) - Chair
Programme
17.15 - 18.15 hrs
Rationale of delivering high precision radiotherapy with the CyberKnife
System for prostate cancer
N. Van As, London (GB)
Delivering radiation differently for patient benefits: Clinical experience of
CyberKnife use
S. Aluwini, Rotterdam (NL)
The PACE study: Comparing surgery, CyberKnife System and conventional
radiation therapy for early stage prostate
N. Van As, London (GB)
Sponsored by ACCURAY
17
Saturday, 17 November 2012
This symposium will take place in Room H1 on level -1
Programme
Symposium
17.15 - 18.15 hrs Extending survival for patients with RCC and CRPC:
New hope in advanced disease
Welcome and introduction
B. Tombal, Brussels (BE) - Chair
Building the optimal sequence in metastatic RCC to maximize survival benefit
C. Porta, Pavia (IT)
Understanding the unmet clinical needs in metastatic CRPC
B. Tombal, Brussels (BE)
Optimizing outcomes in metastatic CRPC: A consideration of new and emerging agents
M. De Santis, Vienna (AT)
Questions and answers
Close
B. Tombal, Brussels (BE)
Sponsored by BAYER
18
Friday, 16 November 2012
All sessions will take place in the main auditorium
Welcome and introduction Urologist W. Artibani, Verona (IT)
Medical oncologist
K. Fizazi, Villejuif (FR)
Radiation oncologistD. Hollywood, Dublin (IE)
Programme
08.15 - 08.30
08.30 - 10.00
Session 1: Treatment of oligometastatic prostate cancer
Chairs:
Urologist
A. Alcaraz, Barcelona (ES)
Radiation oncologistD. Dearnaley, Sutton (GB)
Medical oncologist D. Berthold, Lausanne (CH)
08.30 - 08.45
Case presentation and voting
Urologist - A. Alcaraz, Barcelona (ES)
08.45 - 09.00
W hat is the optimal diagnostic assessment of low-volume bone
metastases?
Radiologist - F. Lecouvet, Brussels (BE)
Limitation of hormone therapy as single systemic modality in
oligometastatic prostate cancer
Urologist - N. Mottet, Saint Etienne (FR)
09.15 - 09.30
Is there a role for local treatment in oligometastatic disease?
Radiation oncologist - V. Khoo, London (GB)
09.30 - 10.00
Voting and discussion
10.00 - 10.30
Coffee break and poster viewing
09.00 - 09.15
10.30 - 12.00
Session 2: Multimodality treatment of early CRPC
Chairs:
Urologist
M. Spahn, Bern (CH)
Radiologist N. De Sousa, Surrey (GB)
Medical oncologist J. Bellmunt, Barcelona (ES)
10.30 - 10.45
Case presentation and voting; Urologist - M. Spahn, Bern (CH)
10.45 - 11.00Optimal staging of early CRPC: Should we move away from bone scan
and CT Scan?
Radiologist - A. Padhani, Northwood (GB)
11.00 - 11.15
Role of salvage radical prostatectomy and salvage LND in patients with
non-metastatic CRPC
Urologist - S. Joniau, Leuven (BE)
11.15 - 11.30
edical treatment in the non-metastatic CRPC setting, where do we
M
stand?
Medical oncologist - C. Sternberg, Rome (IT)
11.30 - 12.00
Voting and discussion
19
12.00 - 13.30
Lunch and poster viewing
12.30 - 13.30
Astellas symposium (see page 15)
Programme
13.30 - 15.00
Session 3: Metastatic CPRC: The debate…
Chairs:
Urologist
N. Clarke, Manchester (GB)
Radiation oncologist M. Mason, Cardiff (GB)
Medical oncologist
S. Osanto, Leiden (NL)
13.30 - 13.45
Case presentation and voting
Urologist - N. Clarke, Manchester (GB)
13.45 - 14.00
Chemotherapy
Medical oncologist - S. Culine, Paris (FR)
14.00 - 14.15
Hormonal therapy
Urologist - B. Tombal, Brussels (BE)
14.15 - 14.30
Radionuclide therapy
Radiation oncologist - C. Parker, London (GB)
14.30 - 15.00
Voting and discussion
15.00 - 15.30
Coffee break and poster viewing
15.30 - 17.00
Session 4: What does the future hold in prostate cancer?
Chairs:
UrologistB. Tombal, Brussels (BE)
Radiation oncologist A. Bossi, Villejuif (FR)
Medical oncologist
J. Bellmunt, Barcelona (ES)
15.30 - 15.45
15.45 - 16.00
16.00 - 16.15
The future of biomarkers
Pathologist - M. Rubin, New York (US)
The future of surgery
Urologist - A. Briganti, Milan (IT)
16.15 - 16.30
16.30 - 17.00
The future of imaging
Radiologist - G. Villeirs, Ghent (BE)
The future of external beam radiotherapy and brachytherapy
Radiation oncologist - M. Van Vulpen, Utrecht (NL)
20
The future of medical therapies
Medical oncologist - J. De Bono, Sutton (GB)
Saturday, 17 November 2012
All sessions will take place in the main auditorium
5: Treatment of oligometastastic RCC
Urologist
H. Van Poppel, Leuven (BE)
Radiologist
G. Villeirs, Ghent (BE)
Medical oncologist T. Powles, London (GB)
Programme
08.30 - 10.00
Session
Chairs:
08.30 - 08.45
Case discussion and voting
Medical oncologist - T. Powles, London (GB)
08.45 - 09.00
The role of metastasectomy in the era of targeted therapies
Urologist - P. Mulders, Nijmegen (NL)
09.00 - 09.15
tereotactic radiotherapy for a radioresistant tumor: Breaking the dogma
S
Radiation oncologist - G. De Meerleer, Ghent (BE)
09.15 - 09.30
Optimal initial strategy in oligometastatic RCC
Oncologist - T. Eisen, Cambridge (GB)
09.30 - 09.55
Voting and discussion
09.55 - 10.00 Announcement best unmoderdated poster
10.00 - 10.30
Coffee break and poster viewing
10.30 - 12.00
Session 6: Metastatic RCC: The debate…
Chairs: Urologist
N. Clarke, Manchester (GB)
Radiation oncologist A. Morganti, Rome (IT)
Medical oncologist T. Eisen, Cambridge (GB)
10.30 - 10.45
Case presentation and voting
Radiation oncologist - A. Morganti, Rome (IT)
10.45 - 11.00
Role of cytoreductive nephrectomy
Medical oncologist - T. Powles, London (GB)
11.00 - 11.15
Immunotherapy and vaccines
Urologist - P. Mulders, Nijmegen (NL)
11.15 - 11.30
Targeted therapies
Medical oncologist - T. Eisen, Cambridge (GB)
11.30 - 12.00
Voting and discussion
12.00 - 13.30
Lunch and poster viewing 12.30 - 13.30
Astellas symposium (see page 16)
13.30 - 14.30
Session 7: Testis cancer - Penile cancer
Chairs: Urologist
N. Clarke, Manchester (GB)
Radiation oncologist N. James, Birmingham (GB)
Medical oncologist K. Fizazi, Villejuif (FR)
21
Programme
13.30 - 14.00
Testicular cancer: Changing epidemiology during the cisplatin era
Medical oncologist - S. Fossa, Oslo (NO)
14.00 - 14.30
What’s new in penile cancer management?
Urologist - S. Horenblas, Amsterdam (NL)
14.30 - 15.00
Coffee break and poster viewing
15.00 - 17.00
Session
Chairs:
8: Oral presentations of the best abstracts
Urologist
L. Turkeri, Istanbul (TR)
Radiation oncologist A. Bossi, Villejuif (FR)
Medical oncologist
C. Sternberg, Rome (IT)
O1External beam radiotherapy combined with brachytherapy for
muscle-invasive bladder cancer results in good local control and
bladder sparing outcome in a cohort of 1040 patients
Pieters B.R., Blank L.E.C.M., Koedooder C., Van Os R.M., Van De Kar M.,
Jansen E., Geijsen E.D., Koning C.C.E. (Amsterdam, The Netherlands)
O2 Automated slide scanning microscopy in the diagnosis of
bladder cancer
Donnini A., Maynard D., Wilson P., Wilson A., Thottakam B.M.V.
(Aberdeen, Lymington, United Kingdom)
O3 Urinary proteome in renal cell cancer patients by MALDTOF mass spectrometry; a biomarker-discovering oriented
controlled study
Gardi M., Fanali C., Ragazzi E., Iavarone F., Sacco E., Dal Bianco M.,
Bassi P.F., Castagnola M. (Padova, Rome, Italy)
O4Tivozanib hydrochloride versus sorafenib as initial targeted
therapy for patients with advanced renal cell carcinoma: Results
from the Phase III randomized, open-label, multicenter TIVO-1
trial
Motzer R., Nosov D., Eisen T., Lipatov O., Tomczak P., Lyulko O., Harza
M., Alexeev B.Y., Sternberg C.N., Szczylik C., Jinga V., Zhang J., Strahs
A., Esteves B., Slichenmyer W., Berkenblit A., Hutson T.E. (New York,
Cambridge, Dallas, United States of America; Moscow, Bashkortostan,
Russia; Cambridge, United Kingdom; Poznan, Warsaw, Poland;
Zaporizhia, Ukraine; Bucharest, Romania; Rome, Italy)
O5 Progression free survival (PFS) and overall survival (OS) in
patients receiving 3 targeted therapies (TTs) for metastatic
renal-cell carcinoma (mRCC)
Iacovelli R., Milella M., Santoni M., Di Lorenzo G., Cerbone L., Ortega C.,
Masini C., Giganti M.O., Messina C., De Vincenzo F., Baratelli C., Massari
F., Boccardo F., Sacco C., Mosca A., Atzori F., Lorusso V., Valduga F.,
Baldazzi V., Cinieri S., Primi F., Procopio G. (Rome, Ancona, Napoli,
Roma, Candiolo, Modena, Milano, Bergamo, Bassano, Verona, Italy,
Udine, Novara, Cagliari, Lecce, Trento, Firenze, Brindisi, Viterbo, Italy)
22
O6 Spatially matched in vivo and ex vivo MR metabolic profiles
of prostate cancer – Investigation of correlation with Gleason
score
Selnæs K.M., Gribbestad I.S., Bertilsson H., Wright A.J., Angelsen A.,
Heerschap A., Tessem M.B. (Trondheim, Norway; Nijmegen, The
Netherlands)
O7 Who is surveying our guidelines for active surveillance? The
geographical variation in active surveillance protocols across
cancer networks in England and Wales
Hughes P.F., Nair R., Larner T. (Brighton, United Kingdom)
O8 Predicting late faecal incontinence after high-dose radiotherapy
for prostate cancer: Development of a ready to use paper model
based on artificial neural network analysis
Carrara M., Tomatis S., Rancati T., Fiorino C., Fellin G., Vavassori V.,
Cagna E., Girelli G., Mauro F.A., Pignoli E., Tortoreto F., Valdagni R.
(Milan, Trento, Bergamo, Como, Ivrea, Lugo Di Romagna, Rome, Italy)
O9Androgen deprivation therapy and the risk of myocardial
infarction and stroke, 2002 to 2012: A nationwide Danish
population-based cohort study
Jespersen C.G., NГёrgaard M., Borre M. (Aarhus, Denmark)
O10Enzalutamide, an androgen receptor signaling inhibitor, improves
overall survival, time to first skeletal related event and pain
Mulders P., Fizazi K., Saad F., Sternberg C.N., Taplin M., Miller K.,
Chi K.N., Armstrong A.J., Basch E.M., Heidenreich A., Hirmand M.
(Nijmegen, The Netherlands; Villejuif, France; Montreal, Vancouver,
Canada; Rome, Italy; Boston, Durham, New York, San Francisco, United
States of America; Berlin, Aachen, Germany)
O11Final analysis of a phase I/II study with CV9103: An
intradermally administered prostate cancer vaccine based on
self-adjuvanted mRNA (RNActiveВ®)
KГјbler H., Maurer T., Stenzl A., Feyerabend S., Steiner U., Schostak
M., Schultze-Seemann W., Vom Dorp F., Pilla L., Parmiani G., Hampel
C., Wedel S., Trojan L., Hiller K., Sommerauer M., Jocham D., Birgit
B., Reindl M., Lander T., Kallen K., Gnad-Vogt U., Kurt K. (MГјnchen,
TГјbingen, Berlin, Freiburg, Essen, Mainz, Frankfurt Am Main, Mannheim,
LГјbeck, Germany; Milan, Italy)
O12Salvage stereotactic body radiotherapy for patients with limited
prostate cancer metastases: Deferring androgen deprivation
therapy
Berkovic P., De Meerleer G., Delrue L., Lambert B., Fonteyne V., Lumen
L., Decaestecker K., Villeirs G., Vuye P., Ost P. (Ghent, Belgium)
17.15 - 18.15
Accuray symposium (see page 17)
17.15 - 18.15
Bayer symposium – H1 Room (level -1) (see page 18)
23
Programme
Sunday, 18 November 2012
Programme
All sessions will take place in the main auditorium
08.30 - 10.00
Session 9: Locally advanced bladder cancer
Chairs:
Urologist M. Brausi, Modena (IT)
Radiation oncologist M. Mason, Cardiff (GB)
Medical oncologist M. De Santis, Vienna (AT)
08.30 - 08.45
Case presentation and voting
Urologist - M. Brausi, Modena (IT)
08.45 - 09.00
Role and extent of LND in locally advanced bladder cancer
Urologist - A. Stenzl, TГјbingen (DE)
09.00 - 09.15
Radio-chemotherapy as an alternative to surgery, are we ready to go?
Radiation oncologist - N. James, Birmingham (GB)
09.15 - 09.30
Neo-adjuvant vs. adjuvant chemotherapy in locally advanced bladder
cancer
Medical oncologist - J. Bellmunt, Barcelona (ES)
09.30 - 9.55
Voting and discussion
09.55 - 10.00 Announcement best unmoderdated poster
10.00 - 10.30
Coffee break and poster viewing
10.30 - 12.00
Session 10: Oligometastatic bladder cancer
Chairs:
Urologist
J. Palou, Barcelona (ES)
Radiation oncologist N. James, Birmingham (GB)
Medical oncologist
S. Osanto, Leiden (NL)
10.30 - 10.45
Case presentation and voting
Urologist - J. Palou, Barcelona (ES)
10.45 - 11.00
Role of surgery in oligometastatic TCC
Urologist - J. Catto, Sheffield (GB)
11.00 - 11.15
Role of radiotherapy in low-volume metastatic bladder cancer
Radiation oncologist - N. James, Birmingham (GB)
11.15 - 11.30
Update on medical treatment of advanced TCC
Medical oncologist - D. Berthold, Lausanne (CH)
11.30 - 12.00
Voting and discussion
12.00 - 13.30
Session 11: The role of focal treatment for prostate cancer
Chairs:
Urologist
R. Karnes, Rochester (US)
Radiologist
J. Barentsz, Nijmegen (NL)
Radiation oncologist
V. Khoo, London (GB)
24
The point of view of the pathologist
Pathologist - F. Algaba, Barcelona (ES)
12.15 - 12.30
The point of view of the surgeon
Urologist - J. Catto, Sheffield (GB)
12.30 - 12.45
The point of view of the radiation oncologist
Radiation oncologist - N. Van As, London (GB)
12.45 - 13.00
The point of view of the interventional radiologist
Radiologist - J. FГјtterer, Nijmegen (NL)
13.00 - 13.30
Voting and discussion
13.30 - 14.00
Take home messages
Urologist R. Karnes, Rochester (US)
Radiation oncologist A. Bossi, Villejuif (FR)
Medical oncologist M. De Santis, Vienna (AT)
14.00 - 14.10
Closing remarks
Urologist W. Artibani, Verona (IT)
Medical oncologist K. Fizazi, Villejuif (FR)
Radiation oncologist D. Hollywood, Dublin (IE)
Programme
12.00 – 12.15
25
Programme
Abstracts
Oral Presentations
Abstracts
Unmoderated Poster Presentations
Disclaimer
The statements and the opinions published in this abstract chapter are solely those of the individual
abstract authors and not of the organisers. The abstracts have been printed as submitted. For the
consistency of this publication only a standard language spelling check was made on all abstracts;
it is the decision of the organisers not to edit the abstracts in order not to change any contexts.
27
28th Annual EAU Congress
Register now to benefit from the early bird fee!
www.eaumilan2013.org
Oral Presentations
Oral Presentations
Saturday, 17 November, 15.00 - 17.00 hrs
29
30
O1
External beam radiotherapy combined with brachytherapy for muscle-invasive bladder cancer
results in good local control and bladder sparing outcome in a cohort of 1040 patients
Pieters B.R., Blank L.E.C.M., Koedooder C., Van Os R.M., Van De Kar M., Jansen E., Geijsen E.D.,
Koning C.C.E.
Academic Medical Center/University of Amsterdam, Dept. of Radiation Oncology, Amsterdam, The Netherlands
Oral Presentations
Introduction & Objectives: Several French, Belgian and Dutch radiation oncologists have reported good
results with the combination of limited surgery followed by external beam radiotherapy and brachytherapy
in early stage muscle-invasive bladder cancer to avoid standard cystectomy. This approach has seldom
been followed by others. This retrospective observational study investigates treatment outcome in the
largest cohort of patients treated by brachytherapy for early stage muscle-invasive bladder cancer.
Material & Methods: Data from 12 out of 13 departments in The Netherlands using this approach have
been collected and imported in a multicenter database The number of patients of this cohort was 1040.
Patients were treated by external beam radiotherapy (10-55 Gy) and brachytherapy (25-40 Gy and 50-60
Gy). In 247 cases a partial cystectomy was performed. Results were analyzed according to tumor stage
and diameter, histology grade, age and brachytherapy technique (Continuous Low Dose Rate (CLDR) and
Pulsed Dose Rate (PDR)).
Results: The age of patients ranged from 28 to 92 years. The gender distribution was 811 males and 229
females. There were 1 pTa, 2 pT0, 126 pT1, 797 pT2, 100 pT3, 4 pT4, and 10 pTx tumors. The distribution
of differentiation grade was 13 well, 167 moderately, 824 poorly, 16 undifferentiated, and 20 unknown.
At 1, 3 and 5 years local control rates were 91%, 80%, and 75%, metastasis-free survival rates were
91%, 80%, and 74%, disease-free survival rates were 85%, 68%, and 61% and overall survival rates were
91%, 74%, and 62%, respectively. There were 136 patients with local recurrences only, 94 with both local
recurrence and distant metastases and 145 with distant metastases only. Of the 232 local recurrences
49 were muscle invasive, 90 were non-muscle invasive, 31 both invasive and non-invasive, and 62 were
unknown. The number of muscle-invasive recurrences for the whole cohort was 8%. Cystectomy as salvage
treatment was performed in 60 patients. The differences in outcome between the contributing departments were small. After multivariate analysis the only factor influencing the local control rate was the
brachytherapy technique in favor of PDR (HR 0.46; P = 0.004).In 2.3% of the patients a fistula and in 13.8%
an ulceration was observed at longer follow-up.
Conclusions: External beam radiotherapy followed by brachytherapy, combined with limited surgery
offers good results in terms of local control and bladder sparing for selected groups of patients suffering
from early-stage muscle-invasive bladder cancer. Treatment outcome is comparable to cystectomy series.
These patients should be counseled on the possibility for a bladder sparing procedure by the use of
brachytherapy.
31
O2
Automated slide scanning microscopy in the diagnosis of bladder cancer
Donnini A.1, Maynard D.2, Wilson P.2, Wilson A.3, Thottakam B.M.V.1
Cytosystems Ltd, Dept. of Research and Development, Aberdeen, United Kingdom, 2Scorpion Vision Ltd,
Dept. of Research and Development, Lymington, United Kingdom, 3Robert Gordon University, Dept. of
Statistics, Aberdeen, United Kingdom
Oral Presentations
1
Introduction & Objectives: In recent years extensive research has been carried out in identifying possible urinary markers that may be useful in the diagnosis of bladder cancer. Previous studies have identified
Minichromosome maintenance protein-2 (MCM-2) as a suitable biomarker. The detection of MCM-2 positive
bladder cancer cells in a urine liquid-based cytology (LBC) slide preparation has been found to be a reliable,
non-invasive screening test for bladder cancer. In order to improve the efficiency and accuracy of this
bladder cancer test, an automated slide scanning microscope has been developed. The Cytosystems Slide
Scanning Automation System (CSSAS) is designed for the automated analysis of MCM-2 positive bladder
cancer cells in a urine LBC preparation. The aim of this study was to evaluate the reproducibility and the
reliability of the CSSAS in detecting bladder cancer.
Material & Methods: Slides were analysed using the CSSAS and a single test was applied, namely
the number of stained MCM positive cells per slide. For the reproducibility test a total of 10 slides were
analysed and each slide was scanned 5 times. The accuracy of the CSSAS was evaluated in a group of 45
patients of whom 17 had biopsy positive bladder cancer and 28 were biopsy negative. Of the 17 biopsy
positive patients, 10 presented with gross haematuria (GH) and 7 were from the cystoscopic surveillance
(CS) group. Statistical analysis (SPSS) was carried out comparing MCM cell counts and biopsy outcomes to
determine the optimum cut-off for MCM positive cells in confirming the diagnosis.
Results: Good repeatability was observed over the 5 MCM measures of 10 slides (Fig. 1). Patient 25 had
no MCM stained cells. Reproducibility was confirmed by the Interclass Correlation Coefficient values of
0.997 and 0.999 for single measures and average measures respectively. Automated MCM cell counts
from patients in GH and CS clinics were analysed both separately and as a single group (all bladder cancers, BC). For the GH group the cut-off for a positive diagnosis was defined at 62 MCM positive cells, giving
sensitivity and specificity of 80% and 100%, respectively. The CS clinic showed an optimum cut-off at 124
stained MCM positive cells, with a sensitivity and specificity of 85.7% and 100%, respectively. For BC the
optimum cut-off was 62, giving sensitivity and specificity of 88.2% and 91.7%, respectively.
Conclusions: This pilot study indicates that the CSSAS may be a useful addition using MCM positive cells
in a non-invasive diagnostic bladder cancer urine test.
32
O3
Urinary proteome in renal cell cancer patients by MALD-TOF mass spectrometry; a biomarkerdiscovering oriented controlled study
Gardi M.1, Fanali C.2, Ragazzi E.3, Iavarone F.2, Sacco E.4, Dal Bianco M.1, Bassi P.F.4, Castagnola M.2, PhD
Programme in Urologic Oncology, Catholic University
1
Ospedale Sant’Antonio, Dept. of UOC Urologia, Padova, Italy, 2Catholic University, Dept. of Biochemistry
and Surgical Biochemistry, Rome, Italy, 3University of Padua, Dept. of Pharmacology and Anestesiology,
Padova, Italy, 4Catholic University, Dept. of Urology, Rome, Italy
Material & Methods: Urine from 52 RCC patients and 40 healthy controls matched by age and sex were
collected. People with chronic renal failure or abnormal urinalysis or diagnosis of any other active tumor or
a history of any other tumor in the last three years were excluded. All samples were purified by Magnetic
Beads based Hydrophobic Interaction Chromatography (MB-HIC) and then analysed by Matrix Assisted
Laser Desorption Ionization – Time of Flight (MALDI-TOF) MS. The MALDI/MS data from urine of RCC
patients and controls were preprocessed using SpecAlign application (version 2.4.1) and then implemented
in MetaboAnalyst web server to obtain data analysis. Univariate analysis using appropriate statistical test
(fold-change, t-test, volcano plot) was carried out in order to detect the presence of discriminant variables.
Cluster Analysis (CA) was used to explore natural spectra groupings; thereafter, Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA) and Random Forest (RF) algorithm were
performed as multivariate analysis. Other urinary proteomic studies in RCC patients and urinary peptides
web-based databases were identified for comparison of results.
Results: Univariate analysis showed 25, 19 and 11 differentially expressed variables between the two
groups, respectively by fold-change, t-test and volcano plot. By means of CA, spectra were observed to
dispose into three groups, comprising respectively the majority of healthy controls, the majority of RCC
patients, and two healthy controls with seven RCC patients. The unsupervised multivariate analysis with
PCA showed that the pick at 1910.8 m/z, underexpressed in RCC patients, account for the 54% of the
variability in the data set, while picks at 2753.9 m/z and 3003.7 m/z account respectively for 12% and
6.4% of variability. The supervised multivariate PLS-DA analysis also identified the pick at 1910.8 as the
most discriminant one. Finally, the RF classification showed a classification error of 0.14 in identifying RCC
patients according to 15 significant features; the 1910.8 m/z pick resulted again the most discriminant.
Significant variables identified in this study were searched in the urinary peptides database HuPA 00670
available at the URL http\\:www.humanproteinpedia.org and found to be expressed in other series of RCC
patients. Moreover, additional five peptides of about 20 considered to be significant were also found to be
significant in an independent study using the same analytical procedure of the present study.
Conclusions: We conclude that RCC patients have a different sub-proteome in the range of small peptides
from healthy controls. We also conclude that a classification model of 15 peptides is quite accurate for
distinguishing RCC patients, with the pick at 1910.8 m/z being the most discriminant one because underexpressed in RCC patients. We stress the inter-laboratory overlapping of these findings.
33
Oral Presentations
Introduction & Objectives: The aim of this study is to compare the peptidomic profile of urine from RCC
patients and healthy controls defined by Mass Spectrometry (MS) analysis focused on small and medium
size peptides (1000-10000 Da).
O4
Tivozanib hydrochloride versus sorafenib as initial targeted therapy for patients with advanced
renal cell carcinoma: Results from the Phase III randomized, open-label, multicenter TIVO-1
trial
Oral Presentations
Motzer R.1, Nosov D.2, Eisen T.3, Lipatov O.4, Tomczak P.5, Lyulko O.6, Harza M.7, Alexeev B.Y.8, Sternberg
C.N.9, Szczylik C.10, Jinga V.11, Zhang J.12, Strahs A.12, Esteves B.12, Slichenmyer W.12, Berkenblit A.12, Hutson
T.E.13
1
Memorial Sloan-Kettering Cancer Center, Dept. of, New York, United States of America, 2N.N. Blokhin
Cancer Research Center, Under The Russian Academy of Medical Sciences, Clinical Pharmac, Dept. of,
Moscow, Russia, 3Cambridge University Health Partners, Dept. of, Cambridge, United Kingdom, 4State Budget Medical Institution, Republican Clinical Oncological Center, Under The Healthcare Minis, Dept. of, Bashkortostan, Russia, 5Clinical Hospital No. 1 of The Poznan University of Medical Sciences, Dept. of, Poznan,
Poland, 6Zaporizhia Medical Academy of Postgraduate Education, Dept. of, Zaporizhia, Ukraine, 7Fundeni
Clinical Institute, Dept. of, Bucharest, Romania, 8Federal State Institution, Moscow Research Oncological
Institute, Dept. of, Moscow, Russia, 9San Camillo Forlanini Hospital, Department of Medical Oncology, Dept.
of, Rome, Italy, 10Military Institute of Health Services, Dept. of, Warsaw, Poland, 11University of Medicine
and Pharmacy �Carol Davila’, Dept. of Urology, Bucharest, Romania, 12AVEO Oncology, Dept. of, Cambridge,
United States of America, 13Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dept. of, Dallas,
United States of America
Introduction & Objectives: Tivozanib hydrochloride (T), a potent, selective, long half-life tyrosine
kinase inhibitor targeting all three VEGF receptors, has shown clinical activity and tolerability in renal
cell carcinoma (RCC) patients (pts). In this Phase III study, we compared T with sorafenib (S) as an initial
targeted treatment for advanced RCC.
Material & Methods: Pts with clear-cell advanced RCC, prior nephrectomy, RECIST-defined measurable
disease, and ECOG performance status (PS) of 0 or 1 were randomized 1:1 to T 1.5 mg once daily for 3
weeks followed by a 1-week rest, or S 400 mg twice daily continuously in a 4-week cycle. Pts had ≤1 prior
systemic therapy for metastatic disease; pts with prior VEGF- or mTOR-targeted therapy were excluded. The
primary endpoint was progression-free survival (PFS) per blinded, independent radiologic review. Adverse
events (AEs) were recorded from time of informed consent until 30 days after last study drug dose.
Results: 517 pts were randomized to T (n=260) or S (n=257). Demographics were balanced between arms,
except for pts with ECOG PS of 0 (T: 44.6% vs S: 54.1%; P=0.035). Median PFS was 11.9 months (mo) for T
vs 9.1 mo for S (HR=0.797, 95% CI 0.639–0.993; P=0.042). In the treatment-naïve stratum (70% of pts in
each arm), the median PFS was 12.7 mo for T vs 9.1 mo for S (HR 0.756, 95% CI 0.580–0.985; P=0.037).
The objective response rate (ORR) in all pts was 33% for T vs 23% for S (P=0.014). The most common AE (all
causality) for T was hypertension and for S was hand–foot syndrome. Other important AEs included diarrhea,
fatigue, and neutropenia. The most common drug-related AEs are shown (Table). Pts receiving T had fewer
drug-related AEs of any grade (Gr) or Gr ≥3 vs S (67.6% vs 83.3% and 36.3% vs 51.0%, respectively).
AEs, %
Tivozanib (n=259)
Sorafenib (n=257)
All Gr
Gr ≥3
All Gr
Gr ≥3
Hypertension
42.1
23.6
30.7
15.2
Dysphonia
18.1
–
4.3
–
Diarrhea
18.1
1.9
27.6
5.8
Hand–foot syndrome
13.1
1.9
53.3
16.7
Fatigue
10.8
2.7
10.9
2.7
Alopecia
2.3
–
20.6
–
Table. Drug-related AEs in ≥10% (safety population)
34
Hypertension was the most frequent T-related AE and was managed with standard antihypertensives. Pts
receiving T had fewer dose interruptions and reductions due to AEs vs pts receiving S (17.8% vs 35.4%
and 11.6% vs 42.8%, respectively), and fewer discontinuations due to drug-related AEs (4.2% vs 5.4%,
respectively). Two deaths in the T arm were due to an MI, and cardiac failure was responsible for 2 deaths
in both the T and S arms.
Oral Presentations
Conclusions: T resulted in significant improvement in PFS and ORR compared with S as initial targeted
treatment for advanced RCC. Pts in the T arm experienced more hypertension and dysphonia, but less
diarrhea, hand–foot syndrome, and alopecia, and had fewer dose interruptions, discontinuations, and
reductions than pts in the S arm.
35
O5
Progression free survival (PFS) and overall survival (OS) in patients receiving 3 targeted
therapies (TTs) for metastatic renal-cell carcinoma (mRCC)
Oral Presentations
Iacovelli R.1, Milella M.2, Santoni M.3, Di Lorenzo G.4, Cerbone L.5, Ortega C.6, Masini C.7, Giganti M.O.8,
Messina C.9, De Vincenzo F.10, Baratelli C.11, Massari F.12, Boccardo F.13, Sacco C.14, Mosca A.15, Atzori F.16,
Lorusso V.17, Valduga F.18, Baldazzi V.19, Cinieri S.20, Primi F.21, Procopio G.22
1
Sapienza University of Rome, Dept. of Radiology Oncology and Human Pathology, Rome, Italy, 2Regina
Elena National Cancer Institute, Dept. of Medical Oncology, Rome, Italy, 3UniversitГ Politecnica Delle Marche, Dept. of Oncology, Ancona, Italy, 4UniversitГ Federico II Napoli, Dept. of Oncology, Napoli, Italy, 5San
Camillo-Forlanini Hospital, Dept. of Oncology, Roma, Italy, 6Istituto Per La Ricerca E La Cura Del Cancro,
Dept. of Oncology, Candiolo, Italy, 7Azienda Ospedaliero Universitaria, Policlinico Di Modena, Dept. of
Oncology, Modena, Italy, 8Niguarda CГ Grande Hospital, Dept. of Oncology, Milano, Italy, 9Ospedali Riuniti
Di Bergamo, Dept. of Oncology, Bergamo, Italy, 10Istituto Clinico Humanitas, Dept. of Oncology, Milan, Italy,
11
San Luigi Bassano Hospital, Dept. of Medical Oncology, Bassano, Italy, 12Azienda Ospedaliera Universitaria Integrata Verona, Dept. of Medical Oncology, Verona, Italy, 13Istituto Nazionale Per La Ricerca Sul
Cancro Di Genova, Dept. of Medical Oncology, Italy, Italy, 14University Hospital of Udine, Dept. of Medical
Oncology, Udine, Italy, 15AOU Maggiore Della CaritГ , Dept. of Medical Oncology, Novara, Italy, 16University Hospital of Cagliary, Dept. of Medical Oncology, Cagliari, Italy, 17Polo Oncologico Vito Fazzi, Dept. of
Medical Oncology, Lecce, Italy, 18Ospedale St. Chiara, Dept. of Medical Oncology, Trento, Italy, 19Careggi
University Hospital, Dept. of Medical Oncology, Firenze, Italy, 20Sen. A.Perrino Hospital, Dept. of Medical
Oncology, Brindisi, Italy, 21Belcolle Hospital, Dept. of Medical Oncology, Viterbo, Italy, 22Fondazione IRCCS
National Institute of Tumors, Dept. of Oncology, Milan, Italy
Introduction & Objectives: In recent years, TTs have improved the prognosis of mRCC patients (pts).
Despite a not negligible number of pts received 3 TTs in clinical practice, no TTs have been evaluated as
3rd line. Aim of this study is to investigate the clinical outcome in pts who received 3 TTs.
Material & Methods: Pts with clear-cell mRCC who received 3 TTs were included. A questionnaire was
sent to main Italian centers involved in the treatment of mRCC. Demographic data, history of RCC, type and
length of first, second and third line were collected; MSKCC risk class was calculated before starting the
1st and 3rd lines, Heng class before the 3rd line. Sequences of class and specific TTs were evaluated: TKIГ TKIГ mTOR and TKIГ mTORГ TKI or sunitinib(SU)-sorafenib(SO)- everolimus(EV) and SU-EV-SO. Median PFS, OS
and Time to Strategy Failure (TTSF: from start of 1st to end of 3rd line) were estimated with the KaplanMeyer method with 95%CI and curves were compared with log-rank test. The study had the ethical approval.
Results: 1905 pts were screened and 252 pts (13%) were treated with 3 TTs. The median age was 60 yrs
(range 52-68), 73% were male, 96% underwent nephrectomy and 38% were metastatic at diagnosis. At 1st
line, the Motzer class was good, intermediate, and poor in 48%, 47% and 5% of pts, respectively. PFS for
type and line of therapy are reported in the table below.
Therapy
Sunitinib
1st line
2nd line
3rd line
%
PFS
%
PFS
%
PFS
60
10.1
31
11.2
8
14.1
Sorafenib
25
13.1
35
7.7
28
5.2
Pazopanib
2
6.4
0
/
0
/
Bevac.+IFN
11
11.3
0
/
1
4.3
Everolimus
0
/
30
4.7
55
6.9
Temsirolimus
2
5.1
3
5.6
5
2.6
Other
0
/
0
/
3
3.2
TOTAL
100
11.6
100
6.8
100
6.2
36
The TTSF was 36.4 (30.5 – 42.2) vs. 30.6 (26.5 – 34.6) mos (p=0.11), and the OS was 52.1 (41.6 – 62.6)
vs. 36.3 (31.2 – 41.4) mos (p=0.01), for TKIà TKIà m-TOR and and TKIà m-TORà TKI, respectively. TTSF for
SU-SO-EV was 36.5 vs. 30.4 mos for SU-EV-SO (p=0.011). When stratified by ECOG-PS before 3rd line or
baseline MSKCC, TS maintained its independent prognostic role (p=0.002 and p=0.004, respectively).
Oral Presentations
Conclusions: Only few patients received 3 lines of TTs. The sequence sunitinib-sorafenib-everolimus was
associated with a better TTSF and OS as compared to the sequence sunitinib-everolimus-sorafenib.
37
O6
Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer – Investigation of
correlation with Gleason score
Selnæs K.M.1, Gribbestad I.S.1, Bertilsson H.2, Wright A.J.3, Angelsen A.2, Heerschap A.3, Tessem M.B.1
Norwegian University of Science and Technology, Dept. of Circulation and Medical Imaging, Trondheim,
Norway, 2St. Olavs Hospital, Trondheim University Hospital, Dept. of Urology, Trondheim, Norway,
3
Radboud University Nijmegen Medical Center, Dept. of Urology Radiology, Nijmegen, The Netherlands
Oral Presentations
1
Introduction & Objectives: Magnetic resonance (MR) metabolic profiling of the prostate is promising
as an additional diagnostic approach to separate indolent from aggressive prostate cancer. Metabolic
profiles of tissue can be obtained non-invasively from patients by in vivo magnetic resonance spectroscopic imaging (MRSI) or ex vivo from tissue samples by high resolution magic angle spinning (HR-MAS) MRS.
Both in vivo and ex vivo studies have revealed a trend towards increased (choline+creatine)/citrate (CC/C)
ratio with increased Gleason score. The objective of this study was to assess the relationship between
Gleason score and the metabolic biomarker (choline+creatine+spermine)/citrate (CCS/C) measured by ex
vivo HR-MAS MRS and in vivo MRSI, and to evaluate the correlation between in vivo and ex vivo measured
metabolite ratios from spatially matched prostate regions.
Material & Methods: Patients (n=13) underwent in vivo MRSI prior to radical prostatectomy. Tissue samples (n=40) for ex vivo analyses were excised from a 2 mm transversal prostate slice according to a new
harvesting method(1). The location of the excised tissue samples were matched to in vivo MRSI voxels (Fig.
1). In vivo MRSI was performed on a 3T clinical MR system and ex vivo HR-MAS on a 14.1T magnet. Relative
metabolite concentrations were calculated by LCModel fitting (2) of in vivo spectra and by peak integration
of ex vivo spectra. Spearman’s rank correlations (ρ) between CCS/C from in vivo and ex vivo MR spectra
and between metabolite ratios and their corresponding Gleason score were calculated.
Results: There was a strong positive correlation between Gleason score and CCS/C measured both in vivo
and ex vivo (r=0.77 and r=0.69, respectively, p<0.001), and between in vivo and ex vivo metabolite ratios
from spatially matched regions (ПЃ=0.67, p<0.001) (Fig. 2).
Conclusions: Our data indicates that MR metabolic profiling may be useful in assessment of prostate cancer aggressiveness during a clinical MRI examination. Moreover, the good correlation between in vivo and
ex vivo measured CCS/C indicates that HR-MAS spectra adequately represent the in vivo metabolic profile
of prostate cancer. References:1) Bertilsson, Prostate 2011 2) Provencher, Magn Reson Med 1993.
38
O7
Who is surveying our guidelines for active surveillance? The geographical variation in active
surveillance protocols across cancer networks in England and Wales
Hughes P.F., Nair R., Larner T.
Brighton & Sussex University Hospitals, Dept. of Urology, Brighton, United Kingdom
Oral Presentations
Introduction & Objectives: Clinical guidelines are an established tenant of modern medical practice with
the aim of adopting best practice, standardising and improving patient care. Although optimal treatment
strategies for “low risk” prostate cancer remain to be determined, National Institute for Clinical Excellence
(NICE) recommends offering Active Surveillance as first line option in patients eligible for radical treatment.
However there is an absence of long-term validated follow-up protocols for PSA monitoring, timing and role
of repeat biopsies or thresholds for intervention. The interpretation of what is meant by Active Surveillance
therefore remains open to debate and variation. We review the geographical variation that exists in Active
Surveillance protocols across cancer networks in England and Wales.
Material & Methods: The Prostate Cancer clinical guidelines from all 33 Cancer Networks across
England and Wales were sought. Details of active surveillance policies for patients with a life expectancy
of more than 10 years were available for 21 networks. Comparisons were made concerning their entry
criteria, follow-up protocols and indications for radical treatment.
Results: Between networks there was little overall consensus. Disparities existed in their entry criteria
(Gleason grading, presenting PSA, the role of PSA densities), the role of trans-perineal biopsies before
commencing surveillance, the frequency and duration of PSA monitoring, the timing and number of rebiopsies, and finally in their definitions of cancer progression. Entry Criteria
Study Type
Pooled OR
95% CI
Study Type
Pooled OR
95% CI
DNA Based(n=22)
2.30
1.04 to 5.10
PCR Based (n=17)
2.63
1.03 to 6.73
No-PCR Based (n=5)
1.49
0.37 to 6.02
No-DNA Based (n=6)
3.26
1.54 to 6.93
3+3
3+4
PSA
PSA
density
Core Number
mm / %
T Stage
Transperineal biopsies prior
Yes (21)
Yes (17)
<10 (6)
<0.15 (3)
1 (1)
<10% (1)
T1c (3)
Yes (5)
В No (4)
<15 (1)
<0.20 (1)
<3 (1)
<20% (1)
T2 (15)
No (16)
В В <20
N/A (17)
<50% (4)
<50% (2)
N/A (3)
В В В N/A (4)
В small volume (2)
<10mm (4)
В В В В В В N/A (13)
Small (2)
В В В В В В В N/A 11
В В 39
Oral Presentations
Monitoring protocols
PSA Monitoring
Re-biopsy timing
DRE
3 monthly (12)
6 months and 12-24 months (1)
4 monthly (1)
4 monthly (1)
8 months (1)
3-6 monthly (1)
6 monthly (1)
12 months (2)
Annual (5)
Clinician's preference (3)
Annual (1)
No detail (14)
No detail (4)
12 -18 months (2)
В В 12-24 months (2)
В В 18 months (1)
В В 18 months, 3 years and 5
years (1)
В В 1, 4 and 7 years (5)
В В Clinicians preference (3)
В В Not absolutely required (1)
В Discontinuation
Patient's choice
All
Biopsy migration
All
PSA - rising
3
PSA >10
4
PSA Doubling Time <10months
1
PSA Doubling Time <2 years
1
PSA Doubling Time <2-4 years
3
PSA Velocity >0.75ng/ml/year
1
PSA Velocity >1.0ng/ml/year
3
DRE migration
5
No details
1
Conclusions: Significant variations exist across cancer networks in England and Wales in terms of what
constitutes an active surveillance programme. National and european guidelines are based on non-mature
randomised trials with a follow-up of less than 10 years. Indicators for entry and disease progression are
poorly defined. Consequently each Network panel makes a judgement of what the best available evidence
suggests in designing their own protocols. It is therefore crucial that each network and urology department
are aware of their own progression rates and that they highlight these uncertainties and controversy when
counselling patients. We await the validated outcomes of ProtecT and START studies to help facilitate
future protocol designs.
40
O8
Predicting late faecal incontinence after high-dose radiotherapy for prostate cancer:
Development of a ready to use paper model based on artificial neural network analysis
Carrara M.1, Tomatis S.1, Rancati T.2, Fiorino C.3, Fellin G.4, Vavassori V.5, Cagna E.6, Girelli G.7, Mauro F.A.8,
Pignoli E.1, Tortoreto F.9, Valdagni R.10
Introduction & Objectives: To study the application of artificial neural network (ANN) classification for
the prediction of late faecal incontinence (LFI) following high-dose prostate cancer radiotherapy (RT) and to
develop a “ready to use” paper tool based on this model.
Material & Methods: 586 men recruited in the AIROPROS 0102 trial, which included the prospective
evaluation of acute and LFI through self-assessed questionnaires, were analyzed. For the present study, a
longitudinal definition of LFI expressed as the average score over three years of late incontinence (G0-G4
grade scale) was considered. Information was recorded on co-morbidity, previous abdominal surgery and
use of drugs. Rectal dose-volume histograms of the whole treatment were recorded for all patients and
the percent volumes of rectum receiving more than 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 Gy (named
V20GyГ V70Gy) were considered. The overall population was split into train and test sets. The train group
was used to optimize the inner weights and biases of the ANN whereas the test set was used as an independent set to verify accuracy and generalization capabilities of the model. A value of longitudinal LFI equal
or greater than one was arbitrarily considered as the endpoint, because this score selected those patients
with persistent symptoms.
Results: Of the 586 patients, 36 had an incontinence score greater than 0 on the baseline pre-treatment
questionnaire and were excluded from the analysis. Thus, the number of patients available for the analysis
was 550, which were split in 366 (15 positive) and 184 (7 positive) cases for train and test set, respectively. Among the large amount of possible ANN input data, a suitable subset of variables able to better
predict late faecal incontinence was selected by simulating more than 10000 different ANN configurations.
Five variables were identified, i.e., the V40Gy (continuous variable), surgery (yes/no), seminal vesicles
irradiation (yes/no), use of anticoagulants (yes/no), and presence of haemorrhoids (yes/no). The resulting
ANN classifier (4 hidden neurons) was able to correctly predict LFI with sensitivity and specificity values of
80% and 68%, respectively for the overall population. Following ROC analysis, area under the ROC curve
was 0.84. For each possible permutation of the four yes/no variables a representation of LFI probability vs
the dosimetric V40Gy continuous value was finally obtained to graphically evaluate LFI probability without
the use of a computer.
Conclusions: ANN analysis combined to the selection of significant input variables and a longitudinal definition of LFI resulted to be a powerful tool to predict late rectal morbidity in patients treated for prostate
cancer. The graphical representation of LFI probability vs the dosimetric V40Gy variable represents an
ANN-based “ready and easy to use” paper tool.
41
Oral Presentations
1
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Medical Physics, Milan, Italy, 2Fondazione IRCCS
Istituto Nazionale Dei Tumori, Prostate Cancer Program, Milan, Italy, 3Istituto Scientifico San Raffaele,
Dept. of Medical Physics, Milan, Italy, 4Ospedale Santa Chiara, Dept. of Radiotherapy, Trento, Italy, 5Humanitas Gavazzeni, Dept. of Radiotherapy, Bergamo, Italy, 6Ospedale Sant’Anna, Dept. of Radiotherapy, Como,
Italy, 7Ospedale ASL 9, Dept. of Radiotherapy, Ivrea, Italy, 8Ospedale Villa Maria Cecilia, Dept. of Radiotherapy, Lugo Di Romagna, Italy, 9Ospedale Isola Tiberina, Dept. of Radiotherapy, Rome, Italy, 10Fondazione
IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program and Dept. of Radiation Oncology 1, Milan,
Italy
O9
Androgen deprivation therapy and the risk of myocardial infarction and stroke, 2002 to 2012:
A nationwide Danish population-based cohort study
Jespersen C.1, NГёrgaard M.2, Borre M.1
Aarhus University Hospital, Skejby, Dept. of Urology, Aarhus, Denmark, 2Aarhus University Hospital, Dept.
of Clinical Epidemiology, Aarhus, Denmark
1
Oral Presentations
Introduction & Objectives: During recent years widespread research have focused on an association
between androgen deprivation therapy in the treatment of prostate cancer and an increased risk of cardiovascular diseases, including myocardial infarction and stroke, but consensus on the topic has not yet been
established.
Material & Methods: We conducted a national cohort study of all patients with incident prostate cancer
registered in the Danish Cancer Registry from January 1st 2002 through 2010. We identified patients
diagnosed with myocardial infarction or stroke after date of initiation of medical endocrine therapy
(gonadotropin-releasing hormone agonists/anti-androgens) or bilateral orchiectomy through the Danish National Patient Registry, from January 1st 2002 to February 16th 2012. We used Cox regression analysis to
estimate hazard ratios of myocardial infarction and stroke, comparing patients treated with either medical
endocrine therapy or orchiectomy with those not treated with medical endocrine therapy or orchiectomy,
adjusting for age, prostate cancer stage, comorbidity, and calendar period.
Results: Of 31,571 prostate cancer patients, 9,204 (29%) received medical endocrine therapy and 2,060
(7%) were orchiedectomized. In patients treated with medical endocrine therapy the adjusted hazard ratio
of myocardial infarction was 1.28 (95% CI 1.12-1.47), and of stroke 1.22 (95% CI 1.07-1.38) compared with
nonusers of androgen deprivation therapy. The adjusted hazard ratio of myocardial infarction and stroke
after orchiectomy was 0.95 (95% CI 0.74-1.23) and 1.03 (95% CI 0.83-1.29), respectively.Crude and adjusted hazard ratios (HR) of myocardial infarction and stroke in 31,571 prostate cancer patients by androgen
deprivation therapy status.
Variables
No of patients
HR (95% CI)
Myocardial infarction
n (%)
Crude
HR (95% CI)
Stroke
Adjusted*
Crude
Adjusted*
Overall
31,571
В В В В No androgen deprivation
therapy
20,307 (64)
1.0 (reference)
1.0 (reference)
1.0 (reference)
1.0 (reference)
Medical endocrine therapy
9,204 (29)
1.37 (1.21-1.56)
1.28 (1.12-1.47)
1.31 (1.17-1.48)
1.22 (1.07-1.38)
Bilateral orchiectomy
2,060 (7)
1.71 (1.35-2.16)
0.95 (0.74-1.23)
1.88 (1.53-2.31)
1.03 0.83-1.29)
*Adjusted for age, prostate cancer stage, comorbidities, and calendar period
Conclusions: In this nationwide cohort study of more than 30,000 prostate cancer patients, we found that
endocrine hormonal therapy was associated with a significantly increased risk of both myocardial infarction
and stroke. In contrast, we did not find this association after orchiectomy.
42
O10
Enzalutamide, an androgen receptor signaling inhibitor, improves overall survival, time to first
skeletal related event and pain
Mulders P.1, Fizazi K.2, Saad F.3, Sternberg C.N.4, Taplin M.5, Miller K.6, Chi K.N.7, Armstrong A.J.8, Basch
E.M.9, Heidenreich A.10, Hirmand M.11
Introduction & Objectives: Enzalutamide-proposed INN (MDV3100), a novel androgen receptor (AR)
signaling inhibitor, inhibits binding of androgens to AR, AR nuclear translocation, and binding of AR with
DNA. The double-blind, multinational phase 3 AFFIRM trial assessed the efficacy and safety of enzalutamide
(ENZA) in men with post-docetaxel metastatic castrate-resistant prostate cancer (mCRPC).
Material & Methods: Patients (pts) were randomized to ENZA 160 mg/d or placebo (PBO); corticosteroids were allowed (not required). Pts were stratified by baseline Eastern Cooperative Oncology Group
Performance Status (ECOG PS) and mean Brief Pain Inventory-Short Form question #3 score (BPI-SF Q3).
Primary endpoint was overall survival (OS). Secondary endpoints included radiographic progression-free
survival (rPFS), time to PSA progression (TTPP), soft tissue objective response rate (ORR), PSA response
(>50% decline), time to first skeletal-related event (SRE: bone radiation therapy/surgery/pathologic fracture; spinal cord compression; change of antineoplastic therapy to treat bone pain), BPI-SF pain severity,
BPI-SF pain interference with activities, pain palliation (≥30% decline in the mean BPI-SF Q3 score over 7 d
at wk 13 vs baseline, without ≥30% increase in analgesics), safety.
Results: Median treatment durations were 8.3 mo for ENZA (n=800 pts) and 3.0 mo for PBO (n=399 pts).
Both groups showed well balanced baseline characteristics; 38% ENZA vs 38% PBO pts had >20 bone
and 25% ENZA vs 21% PBO pts had visceral liver/lung lesions. Overall pt demographics were: median age,
69 y; white, 93%; mean BPI-SF Q3 score ≥4, 28%; ECOG PS <2, 92%; median PSA, 111 ng/mL. European
demographics (n=684) were similar: age, 69 y; white, 97%; BPI-SF Q3 ≥4, 26%; ECOG PS <2, 93%; PSA,
113 ng/mL. Overall Population Results
Endpoint
ENZA
PBO
HR (95% CI)
P-value
Median OS, mo
18.4
13.6
0.631 (0.529-0.752)
<0.0001
Median rPFS, mo
8.3
2.9
0.404 (0.350-0.466)
<0.0001
Median TTPP, mo
8.3
3.0
0.248 (0.204-0.303)
<0.0001
ORR (CR+PR), %
28.9
3.8
-
<0.0001
PSA response, %
54.0
1.5
-
<0.0001
Median time to first SRE, mo
16.7
13.3
0.688 (0.566-0.835)
0.0001
Pain Palliation,%
44.9
6.7
-
0.0079
Mean BPI-SF pain severity and interference were reduced by 0.65 and 0.76, respectively, with ENZA vs
PBO (both P<0.001). In evaluable pts with baseline and wk 13 BPI-SF Q3 scores, 28% ENZA and 39% PBO
pts (P=0.0018) had pain progression (increased mean BPI-SF Q3 score vs baseline). Median time to pain
progression (increased FACT-P “I have pain” score) was not yet reached for ENZA vs 13.8 mo for PBO
(P=0.0004, HR 0.564 [0.409-0.777]). The most frequently reported adverse event occurring more often in
ENZA pts was fatigue (34% ENZA, 29% PBO).
43
Oral Presentations
1
Radboud University Medical Centre, Dept. of Urology, Nijmegen, The Netherlands, 2University of Paris
Sud, Dept. of Cancer Medicine, Villejuif, France, 3University of Montreal Hospital Center, Dept. of Surgery,
Montreal, Canada, 4San Camillo Forlanini Hospitals, Dept. of Medical Oncology, Rome, Italy, 5Dana-Farber
Cancer Institute, Dept. of Genitourinary Oncology, Boston, United States of America, 6Charité - Universitätsmedizin Berlin, Chirurgische Medizin, Klinik Für Urologie, Berlin, Germany, 7British Columbia Cancer
Agency, Experimental Therapeutics, Vancouver, Canada, 8Duke University, Medicine, Durham, United States of America, 9Memorial Sloan-Kettering Cancer Center, Medicine, New York, United States of America,
10
University Hospital Aachen, Dept. of Urology, Aachen, Germany, 11Medivation, Inc., Medivation, Inc., San
Francisco, United States of America
Oral Presentations
Conclusions: ENZA significantly prolongs OS, slows disease progression and time to first SRE, improves
measures of pain, and was generally well tolerated in men with mCRPC.
44
O11
Final analysis of a phase I/II study with CV9103: An intradermally administered prostate cancer
vaccine based on self-adjuvanted mRNA (RNActiveВ®)
1
Klinikum Rechts Der Isar Der TU München, Urologische Klinik und Poliklinik, Munich, Germany, 2Universitaetsklinikum Tübingen, Klinik für Urologie, Tübingen, Germany, 3Charité Universitätsmedizin Berlin Campus
Benjamin Franklin, Urologische Klinik und Hochschulambulanz, Berlin, Germany, 4Universitätsklinikum Freiburg, Abteilung Urologie, Freiburg, Germany, 5Universitätsklinikum Essen, Klinik und Poliklinik für Urologie,
Uroonkologie und Kinderurologie, Essen, Germany, 6Istituto San Raffaele, UnitГ Di Immuno-Bioterapia Dei
Melanomi e Dei Tumori Solidi - Fondazione Scientifica, Milan, Italy, 7Johannes-Gutenberg-Universität Mainz,
Urologische Klinik und Poliklinik, Mainz, Germany, 8Klinikum Der JWG-Universität, Klinik für Urologie und
Kinderurologie, Frankfurt Am Main, Germany, 9Universitätsmedizin Mannheim, Urologische Klinik,
Mannheim, Germany, 10UKSH Campus LГјbeck, Klinik und Poliklinik fГјr Urologie, LГјbeck, Germany,
11
CureVac GmbH, Immunomonitoring, TГјbingen, Germany, 12CureVac GmbH, Clinical Development,
TГјbingen, Germany
Introduction & Objectives: To test the safety and immunogenicity of the RNActiveВ®-derived prostate
cancer vaccine CV9103 in patients with castrate-resistant disease. CV9103 comprises four self-adjuvanted
mRNA compounds encoding the full-length antigens PSA, PSCA, PSMA and STEAP1.
Material & Methods: In the Phase I part, the primary objective was the selection of a recommended dose
(RD) based on safety data. 3 mRNA dose levels (256Вµg, 640 Вµg and 1280Вµg) were explored. Objectives of
the Phase II part were the evaluation of safety, immune responses and anti-tumor activity. Over a period of
23 weeks 5 vaccinations with CV9103 were administered intra- dermally. Blood samples for immunomonitoring were taken at baseline and two weeks after the 2nd, 3rd and 4th vaccination, respectively. Antigen
specific cellular immune response was assessed by ex vivo ELISPOT (IFN-g), intracellular cytokine staining
(IFN-g, TNFa) and tetramer analysis (only HLA-A2+ patients), and induction of anti-PSA antibodies by ELISA
(IgG and IgM). PSA serum levels were assessed at pre-specified time points.
Results: 44 patients with castrate resistant prostate cancer and rising PSA were included. In phase I,
1280Вµg was confirmed as recommended dose and further explored in the phase II part. The most frequently reported related adverse events were injection site reactions, fatigue and fever which were mild to moderate in severity. immunomonitoring was performable in 33 of the 38 patients treated at the recommended
dose. Antigen-specific immune responses were detected in 79% of patients and 58% of the immunological
responders reacted against multiple antigens. Immune responses were detected against all 4 antigens
regardless of cellular localization. Additionally, an increased frequency of antigen-unspecific B-cells was observed in 74% of patients, and NK-cells showed a tendency of increased activation (up-regulation of CD25
and CD69) Median PSA PFS from time of first vaccination was 1.6 months (95% CI 1.4 to 2.9). One patient
had a drop greater than 85% of his serum PSA. Overall survival data will be presented.
Conclusions: CV9103 was shown to be safe, well-tolerated and induced a high level of antigen specific immune responses. The clinical efficacy of RNActiveВ® vaccination will be assessed in a randomized phase II
trial in patients with asymptomatic or mildly symptomatic castration refractory prostate cancer with overall
survival as primary endpoint.
45
Oral Presentations
KГјbler H.1, Maurer T.1, Stenzl A.2, Feyerabend S.2, Steiner U.3, Schostak M.3, Schultze-Seemann W.4, Vom
Dorp F.5, Pilla L.6, Parmiani G.6, Hampel C.7, Wedel S.8, Trojan L.9, Hiller K.9, Sommerauer M.10, Jocham D.10,
Birgit B.11, Reindl M.12, Lander T.12, Kallen K.12, Gnad-Vogt U.12, Kurt K.3
O12
Salvage stereotactic body radiotherapy for patients with limited prostate cancer metastases:
Deferring androgen deprivation therapy
Berkovic P.1, De Meerleer G.1, Delrue L.2, Lambert B.3, Fonteyne V.1, Lumen L.4, Decaestecker K.4,
Villeirs G.2, Vuye P.1, Ost P.1
1
Ghent University Hospital, Dept. of Radiotherapy, Ghent, Belgium, 2Ghent University Hospital, Dept. of
Radiology, Ghent, Belgium, 3Ghent University Hospital, Dept. of Nuclear Medicine, Ghent, Belgium, 4Ghent
University Hospital, Dept. of Urology, Ghent, Belgium
Oral Presentations
Introduction & Objectives: We investigated whether repeated Stereotactic body radiotherapy (SBRT)
of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in
patients with low-volume bone and lymph node metastases.
Material & Methods: Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emitting tomography, following biochemical recurrence after local curative treatment,
were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free
survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the
primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when
patients were still asymptomatic or in case of a PSA rise above 50ng/ml in the absence of metastases.
Secondary endpoints were local control, clinical progression free survival and toxicity. Toxicity was scored
using the Common Terminology Criteria for Adverse Events.
Results: We treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT
resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression free survival
was 100% and 42% respectively. Eleven and 3 patients respectively required a second and third salvage
treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed.
Conclusions: Repeated salvage SBRT is feasible, well tolerated and defers palliative ADT witha median of
38 months in patients with limited bone or lymph node PCa metastases.
46
Unmoderated Poster Presentations
10.00 - 10.30 hrs
12.00 - 13.30 hrs
15.00 - 15.30 hrs
Saturday, 17 November 10.00 - 10.30 hrs
12.00 - 13.30 hrs
14.30 - 15.00 hrs
Sunday, 18 November 10.00 - 10.30 hrs
Unmoderated
Friday, 16 November Unmoderated
PostersPosters
Poster viewing hours
47
P001
Effect of vinflunine on epithelial-mesenchymal transition in human bladder cancer cell lines
Anton-Aparicio L.M.1, Abella V.1, Haz M.1, Gayo J.2, Figueroa A.1
Unmoderated Posters
1
Instituto De InvestigaciГіn BiomГ©dica A CoruГ±a (INIBIC) Complejo Hospitalario Universitario A CoruГ±a,
Translational Cancer Research Group, A CoruГ±a, Spain, 2Pierre Fabre Iberica, S.A., Divison De Oncologia,
Barcelona, Spain
Introduction & Objectives: Vinflunine is a third-generation, semi-synthetic vinca alkaloid that, similar to
other microtubule-targeting drugs, suppresses microtubule (MT) dynamics both in vitro and in living cancer
cells. It slows down the metaphase-to-anaphase transition, blocks cancer cells in mitosis and induces
apoptosis. Vinflunine is an option treatment for patients with transitional-cell-carcinoma (TTC) progressing
after first-line platinum-containing chemotherapy. In the last ten years, it has been emerging the connection
between MT and cadherins, establishing the impact of MT dynamics on E-cadherin-based cell-cell contacts.
E-cadherin is the prototype and best characterized member of adherens junctions in epithelial cells of
mammals and is regarded as a tumour suppressor. Its loss is associated with poor prognosis in carcinoma,
and it is considered as a hallmark of epithelial-mesenchymal transition (EMT). Here, we study the effect of
vinflunine in bladder TCCs during EMT, attending to its action on E-cadherin expression and its transcriptional and posttranslational regulators.
Material & Methods: Bladder transitional carcinoma cell lines (HT1376, HT1197, SW780, UM- and UMUC-3) were treated with increasing concentrations of vinflunine. To determine the cell viability, it was analyzed the cytotoxicity by MTT assay. The effect of increasing concentrations of vinflunine was determined
by analyzing changes in the cell phenotype by contrast phase microscopy. Moreover, western blotting and
qRTPCR were performed to determine the effect in the expression on important protein markers implicated
during EMT such as E-cadherin, Snail, Slug, Vimentin, Twist 1, Hakai and N-cadherin. Moreover, the effect in
an in vitro invasion assay was determined.
Results: We show that vinflunine, at low noncytotoxic concentrations, reverts the epithelial-mesenchymal
transition in bladder transitional carcinoma cell lines by down-regulating E-cadherin expression and increasing Hakai protein levels.
Conclusions: Our results underscore a new mechanism by which vinflunine exerts its action on the EMT
process, opening a new research approach, particularly in the identification and characterization of new
proteins as new specific targets for vinflunine during invasion and metastasis.
48
P002
Interleukin-8 (IL8) and transforming growth-factor beta (TGF-ОІ) as drugable biomarkers of response, progression-free (PFS) and overall survival (OS) with pazopanib (PZP): A phase 2 study in
relapsed urothelial cancer (UC)
Necchi A.1, Mariani L.2, Zaffaroni N.3, Giannatempo P.1, Nicolai N.4, Raggi D.1, Pennati M.5, Morosi C.6,
Lanocita R.6, Crippa F.7, Daidone M.G.3, Gianni A.M.1, De Braud F.1, Salvioni R.4
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Medical Oncology, Milan, Italy, 2Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Biostatistics, Milan, Italy, 3Fondazione IRCCS Istituto Nazionale
Dei Tumori, Dept. of Experimental Oncology and Molecular Medicine, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Urology, Milan, Italy, 5Fondazione IRCCS Istituto Nazionale Dei Tumori,
Dept. of Experimental Oncology, Milan, Italy, 6Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of
Radiology, Milan, Italy, 7Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Nuclear Medicine, Milan,
Italy
Introduction & Objectives: Final results of INT70/09 trial of PZP in 41 multi-relapsed patients (pts) with
UC reported one of the highest response-rates with antiangiogenic agents as 7 pts (17%) had a confirmed
PR, 14 a confirmed SD (51% clinical benefit) after independent review (AACR & ASCO 2012). Final achievements on circulating biomarkers are presented (ClinicalTrials.gov NCT01031875).
Material & Methods: From 02/2010 to 07/2011, pts received PZP 800 mg once daily until PD or
unacceptable toxicity. 50 mL of EDTA blood samples were collected at baseline (T0) and after 4wks (T1)
together with disease restaging in all pts to analyze plasma levels of VEGF, sVEGFR-1,-2 and -3, c-Kit, HGF,
TGF-ОІ, IL-6, 8 and 12 by multiplex ELISA plates. Changes in marker levels were analysed with the Wilcoxon
signed-rank test while a linear regression model was used to investigate the association between marker
levels at T1 and overall tumor response, using marker levels at T0 as a covariate (covariance analysis for
pre‑post design). A logistic regression and Cox regression model evaluated the association of biomarker
level with response probability, PFS and OS. Biomarker level was modelled as a continuous time-varying
covariate.
Results: Significant increase from T0 to T1 was observed for VEGF (p<0.0001), HGF (p=0.017), IL6
(p<0.0129) and IL8 (p<0.0013) and decrease for VEGFR2 and c-Kit (p<0.0001 each). Increasing IL8T1 level
associated with lower response probability at covariance analysis (p=0.0104). Both TGF-ОІT0 (p=0.0019)
and TGF-ОІT1 (p=0.0017) levels associated with PFS while elevated IL8T0 (p=0.0170), IL8T1 (p=0.0107)
as well as TGF-ОІT0 (p=0.0472) and TGF-ОІT1 (p=0.0013) levels associated with OS. Elevated VEGFT1 also
associated with shorter OS (p=0.0084) but significance was lost when jointly modelling biomarkers. Pts
having IL8T1 levels < 80 pg/ml had greater response (approaching 80%) and 6-month OS (60%) probability
than those with a level ≥ 80, for whom a dramatic fall was observed.
Conclusions: Both IL8 and TGF-ОІ had a prognostic value while IL8 modulation was also associated with
response probability. If confirmed in a larger series, these markers may serve to select pts most likely to
get a benefit from PZP. There is a rationale for a sequence/combination with PZP and a phase 2 study of an
anti-TGF-ОІ receptor ALK1 moAb (PF-03446962) for refractory UC is currently recruiting (ClinicalTrials.gov
NCT01620970).
49
Unmoderated Posters
1
P003
HER2 amplified urothelial bladder cancer: Associations with histopathological tumour
characteristics and genetic analyses
Seiler R.1, Tschui J.2, Vassella E.2, Rotzer D.2, Thalmann G.N.1
1
University Hospital Bern, Dept. of Urology, Bern, Switzerland, 2University Hospital Bern, Dept. of Pathology, Bern, Switzerland
Unmoderated Posters
Introduction & Objectives: Several clinical trials are currently investigating the possible benefit of HER2targeted therapy for urothelial bladder cancer (UBC) with altered HER2 status. However, little is known
about the histomorphology, Her2 protein distribution and occurrence of genetic alterations in such cases.
Material & Methods: One hundred and fifty primary UBC were evaluated in a tissue microarray format
by fluorescence in situ hybridization for HER2 amplification. The histopathological features of the 13 HER2
amplified tumours (8.6%) were compared with 13 matched non-amplified UBC. In addition, HER2-amplified
tumours were evaluated for intratumoural heterogeneity of protein expression by immunohistochemistry on
gross sections and for mutations in exon 20 of the amplicon.
Results: UBC with HER2 amplification presented (a) with a broader variety of histomorphological subtypes,
showing particularly a high frequency of micropapillary tumour components (10/13 vs. 2/13 patients,
p=0.005), and (b) demonstrated a higher amount of tumour associated chronic inflammation (p=0.005)
than the control group. Immunohistochemical stainings revealed a homogenous HER2 protein expression and a score 3+ in 76.9% of our cases. None of the HER2-amplified tumours harboured a mutation in
exon20 of the HER2 gene.
Conclusions: HER2 amplified UBC are morphologically heterogeneous, frequently demonstrate micropapillary growth and show high tumour-associated chronic inflammation. These features may help pathologists to identify these specific tumours.
50
P004
Lymph node positive bladder cancer: CCND1 and CyclinD1 status independently predicts
survival and chemotherapeutic response
Seiler R.1, Fleischmann A.2, Rotzer D.2, Thalmann G.N.1
1
University Hospital Bern, Dept. of Urology, Bern, Switzerland, 2University Hospital Bern, Dept. of
Pathology, Bern, Switzerland
Material & Methods: Hundred and fifty-two patients with bladder cancer underwent cystectomy and
standardized extended pelvic lymphadenectomy in curative intent (preoperatively stages N0M0) and
had positive lymph nodes upon histological examination. Amplification status of the gene CCND1 and
expression of the corresponding protein CyclinD1 were evaluated by fluorescence in-situ hybridization and
immunohistochemistry on tissue microarrays constructed with four tumour samples per patient, two from
primary tumours and two from corresponding lymph node metastases, respectively. CCND1 status and
percentage of immunostained cancer cells were correlated with cancer-specific survival and response to
adjuvant chemotherapy.
Results: CCND1 amplification in primary tumours was homogeneous in 15% and heterogeneous in 6%
(metastases: 22% and 2%). Median nuclear CyclinD1 expression in amplified samples was similar in all tumour compartments (60%-70% immunostained tumour nuclei) and significantly higher than in non-amplified
samples (5%-20% immunostained tumour nuclei; p<0.05). Nuclear CyclinD1 expression was significantly
(p<0.05) up-regulated in metastases (median nuclear expression: 50%) compared to primary tumours
(median nuclear expression: 30%). CCND1 amplification in primary tumours (p=0.001) and metastases
(p=0.02) and high nuclear CyclinD1 in metastases (p=0.01) predicted early cancer-related death independently. Subgroup analyses showed that survival stratification was best in patients without any chemotherapy, all patients with high nuclear CyclinD1 expression died during the first 2.5 years. Importantly, survival of
this high risk subgroup increased dramatically when any chemotherapy (5-year CSS: 22%) and particularly
platin-based chemotherapy (5-year CSS: 37%) was applied while the low risk group did not profit substantially. Expression in primary tumours and CCND1 status did not predict chemotherapeutic response.
Conclusions: CCND1 status and CyclinD1 expression are independent risk factors in metastasizing
bladder cancer. High nuclear CyclinD1 expression in metastases predicts favourable response to
chemotherapy. This information may help to personalize prognostication and administration of adjuvant
chemotherapy.
51
Unmoderated Posters
Introduction & Objectives: CyclinD1 is an important promoter of the cell-cycle. In cancers of the oesophagus and head and neck, this biomarker is a prognostic factor and predicts response to chemotherapy.
There are only sparse data of CyclinD1 in bladder cancer.
P005
Correlation of tissue expression of matrix metalloproteinases and their inhibitors with
recurrence and progression in non-muscle invasive bladder cancer
LГіpez J.M.1, Rodriguez Faba O.1, FernГЎndez J.M.2, Palou J.1, Algaba F.1, Escaf S.3, Vizoso F.3,
Villavicencion H.1
1
FundaciГі Puigvert, Dept. of Urology, Barcelona, Spain, 2Hospital Central De Asturias, Dept. of Urology,
Oviedo, Spain, 3Hospital De Jove, Dept. of Urology, GijГіn, Spain
Unmoderated Posters
Introduction & Objectives: Matrix metalloproteinase (MMPs) and tissue inhibitors of metalloproteinase
(TIMPs) are zinc-dependent endogenous proteases involved in several signalling pathways and extracellular
matrix degradation, providing tumour cells the potential to disseminate. The aim of this study was to
evaluate the relationship between the expression of these proteins with progression and recurrence of
high-risk non-muscle invasive bladder cancer (NMIBC).
Material & Methods: Seventy-seven tissue microarrays from a representative group T1G3 NMIBC
samples were prepared in order to determinate the expression of MMP1, 2, 7, 8, 9, 13, 15, and TIMP1, 2,
3, in epithelium, fibroblast and monocytes. Protein expressions were quantified by image analysis system.
Clinical prognostic factors analysed were: sex, age, CIS, size (>3cm), number of tumours. SPSS 17.0 was
used to perform statistical analysis.
Results: The median follow-up was 59 months (9-136). In our series recurrence and progression rate were
42% and 14%. Cancer specific mortality was 6.5%. Kaplan-Meier curves show a statistically significant association in univariate analysis between MMP2 expression in fibroblasts (p=0,01) and monocytes (p=0,032)
and CIS (p=0,008) with disease progression. Statistically non-significant trend between the expression of
MMP11 (p=0.19) and TIMP (0.12) in fibroblasts and recurrence was found (TIMP as a protector factor). The
multivariate analysis did not found statistical associations.
Conclusions: MMP 2 expression in fibroblasts of neoplastic tissue looks like as a possible indicator of tumour progression that should be confirmed in further studies as a prognostic factor. In this study tumours
that did not express this protein present a low rate of progression. The low rate of progression in this
series may be the reason why there are no statistically significant associations.
52
P006
Study of thirteen methylated genes through DNA bisulfite pyrosequencing for the non-invasive
detection of bladder cancer
Van Der Heijden A.G.1, Mengual L.2, Ingelmo C.2, Mercade Carceller A.M.3, Ribal M.J.2, Alcaraz A.2, Schalken
J.A.1, Witjes J.A.1
Introduction & Objectives: Bladder cancer follow up is based on cystoscopy and urine cytology. Cystoscopy is considered the gold standard, but fails in up to 45% of the papillary and up to 60% of the carcinoma
in situ (CIS) lesions. Furthermore, it is expensive and bothersome for patients. Urine cytology on the other
hand, has a high specificity but lacks sensitivity especially in low risk tumours, besides that it is very
observer dependent. So, there is a need for a reproducible noninvasive method with a high sensitivity and
specificity. Aberrant DNA methylation is a potential marker for prognosis, diagnosis and monitoring disease
after therapy. In this study a panel of thirteen recently described methylated genes are evaluated in urine
samples of patients with bladder cancer and controls.
Material & Methods: Urine samples of 54 consecutive patients with proven bladder carcinoma of all
stages and grades (cases) and 31 samples of patients without a history of bladder cancer (controls) were
collected. In total 13 genes (APC, CCNA1, CDH13, CFTR, GDF15, MINT1, NID2, RARB, RASSF1A, SALL3,
TMEFF2, TWIST1 and VIM) were selected from different recently published studies as a targets for epigenetic silencing in bladder cancer. After bisulfite treatment of isolated urine DNA. A polymerase chain reaction
(PCR) was performed for the selected markers. The PCR product was analyzed by the pyrosequencing
method which has the advantage of determining the ratio of C-to-T at individual sites quantitatively. Data
analysis was performed with SPSS v.16.0.
Results: Overall, 3 to 8 CpG positions within the promoter could be evaluated in all the markers. With a
defined specificity of 100%, CFTR and TWIST1 showed a remarkable higher sensitivity rate (69% and 61
%, respectively) than the other genes. A panel of four markers (CFTR, TWIST1, CDH13 and RASSF1A) was
composed and showed an improved sensitivity of 85% with a specificity of 100% (negative and positive
predictive value of 80% and 100%, respectively).
Conclusions: Our panel of four methylated genes is highly sensitive and specific for the urine-based,
noninvasive detection of bladder cancer, including low-grade and low-stage tumours. Furthermore, our data
show for the first time that the pyrosequencing method is suitable for the methylation analysis of bisulfite
treated DNA extracted from urine samples. This makes the methylation analysis fast and highly reproducible. The four genes panel is currently being validated in a multicentre cross-sectional analysis using over
800 urine samples.
53
Unmoderated Posters
1
Radboud University Nijmegen Medical Centre, Dept. of Urology, Nijmegen, The Netherlands, 2Hospital
Clinic IDIBAPS; Universitat De Barcelona, Dept. of Urology, Barcelona, Spain, 3Universitat Autonoma De
Barcelona, Dept. of Genetics, Barcelona, Spain
P007
Investigation of telomerase activity for development of noninvasive diagnosis of bladder cancer
Polyakovsky K.A.1, Grigorieva Y.E.2, Vinarov A.Z.1, Glukhov A.I.2, Alyaev Y.G.1, Glybochko P.V.1,
Potoldykova N.V.1
1 MSMU, Dept. of Urology, Moscow, Russia, 21 MSMU, Dept. of Biochemistry, Moscow, Russia
Unmoderated Posters
1
Introduction & Objectives: Bladder cancer (BC) is one of the most common types of urinary tract
malignant tumors. In 2006 104400 cases of BC were diagnosed in Europe. 82800 patients were men
and 21600 were women. It accounts for 6,6 of all malignancies among men and for 2,1 among women.
It’s 3,8 times more common in men than in women. BC also is the 4th most common tumor in men. BC
accounts for 3,1% of deaths from malignant tumors among men and 1,8% among women. The most commonly used method for BC diagnosis is cytoscopy and histological analysis of biopsy. These methods are
invasive, expensive and hard to perform. This means that noninvasive method of BC diagnosis should be
set, in particular investigation of BC markers in urine. The aim of our research is an attempt of definition of
active telomerase (AT) and expression of its catalytic subunit hTERT in urine sell sediments for noninvasive
diagnosis of BC.
Material & Methods: For our research we examined samples of urine sediments and tissue samples
from patients with BC. Tissue samples were obtained by transurethral resection of bladder wall, accessible resection of urinary bladder wall and cystectomy. We examined 20 samples of urine sediments and
17 samples of tumor tissue. BC was histologically confirmed in all cases. Further AT in every sample was
determined with TRAP-assay and relative levels of hTERT expression – with RT-PCR. Also all samples were
examined for presence of telomerase inhibitors. In case of inhibitors presence suspicion samples were
secondary tested with dilutions of examining protein lysates for revelation of true AT values.
Results: In obtained urine sediments AT was detected in 16 of 20 cases (80%) and in tissue samples in
17 of 17 cases (100%). In these samples middle level of AT in tissue samples was 2,18 times higher than
in urine sediments samples. The same time expression of hTERT was detected in 4 of 20 urine sediments
samples (17%) and in 4 of 17 of tumor tissue samples (23%). One of the samples didn’t show positive
AT, but its hTERT expression level was high. So, we can suppose that hTERT can carry functions which
aren’t connected with telomerase activity. In this case control analysis didn’t show telomerase inhibitors
presence. According to the scientific data the high level of hTERT expression correlates with the negative
prognosis of tumor diagnosis.
Conclusions: This data shows the possibility of using suggested methods in BC diagnosis. At the same
time these methods should be improved for preserving cell material in cell sediments. Also a number of
patients with different bladder pathologies should be increased for improvement of sensitivity and specific
character of the methods.
54
P008
Monosymptomatic macroscopic painless hematuria in the emergency department:
The importance of a urologic fast circuit for the diagnosis of a bladder tumor
Gual Frau J.1, Campos Gracia C.2, Ferrer Da Pena M.D.2, Garcia Rojo D.1, Gene Tous E.2, Malet Munte A.3,
Barrio MuГ±oz M.1, Fadil Hechadi Y.1, Capdevila Gonzalo M.1, MuГ±oz Rodriguez J.1, Abad Gairin C.1, Gonzalez
Sala J.L.1, Hannaoui Hadi N.1, Martos Calvo R.1, Prera Vilaseca A.1, Vicente Palacio E.1, Prats Lopez J.1
Introduction & Objectives: Hematuria is one of the most frequent urological consultations in the Emergency Departments (ED). The etiology of mono-symptomatic macro-hematuria can be malignant, especially
bladder cancer (BC). The initial diagnostic management is essential in de prognosis of BC. To analyze the
importance of a urological fast circuit (UFC) to prioritize and diagnose patients presenting BC at the ED by
macro-mono-symptomatic hematuria, comparing if differences exist in histological stage and prognosis
between primary bladder tumors diagnosed in the emergency department and those diagnosed in the office of the department of urology.
Material & Methods: Observational, cross-sectional and retrospective analysis by patients consulting to
the ED due to macro-mono-symptomatic hematuria who were referred to early diagnosis UFC-BC between
01.05.2008 and 30.04.2009.Statistics: Chi square test for comparing proportions and Student t-test to
compare means.
Results: Of the 506 episodes of hematuria of the study period, 86 patients with macro-mono-symptomatic
hematuria were referred to UFC, being involved a tumor etiology in 34.9% (30.2% BC). Of the patients with
BC, 69% were men, mean age 72.6 years and mean time between visits to the ED and cystoscopy was
44 В± 18 days. Pathological stage comparing patients diagnosed in the emergency department vs those
diagnosed in office showed: Infiltrant BC 16.6% vs 20.3% (p= 0.1). Superficial low risk BC 25% vs 21.6% (p=
0.1), superficial intermediate risk BC 29.1% vs 28.4% (p=0.7) and superficial high-risk BC 29.1% vs 29.7%
(p= 0.8). In the superficial BC, the average probability of relapse at 1 year was 24.8% vs 27.6% (p= 0.32)
and progression of 3.16% vs. 3.95% (p = 0.53).
Conclusions: The CRU allows to prioritize and to diagnose an important percentage of BC in patients
who consult to the ED with monosymptomatic macrohematuria. There are no differences in pathological
stage and prognosis when comparing patients diagnosed of primary bladder cancer in the emergency
department and those diagnosed in the office of the department of urology. However, the diagnosis and
treatment of these patients should be early, especially in order to not delay the treatment of high grade
superficial tumors and invasive bladder cancers.
55
Unmoderated Posters
1
CorporaciГі Sanitaria Parc Tauli, Dept. of Urology, Sabadell, Spain, 2CorporaciГі Sanitaria Parc Tauli, Dept.
of Emergency, Sabadell, Spain, 3CorporaciГі Sanitaria Parc Tauli, Dept. of Radiology, Sabadell, Spain
P009
Use of the new v-loc auto-static suture for bladder replacement according to “vescica ileale
padovana (vip)” technique
Racioppi M., Filianoti A., Cappa E., D'agostino D., Pinto F., Sacco E., Pugliese D., Bassi P.F.
Catholic University of Sacred Heart, Dept. of Urology, Rome, Italy
Unmoderated Posters
Introduction & Objectives: The phase of creation and reconfiguration of the ileal neobladder after radical
cistectomy affects in a decisive way the length of operation. The use of a self-blocking suture is ideal to
shorten this phase. We are going to introduce the "Vescica Ileale Padovana (VIP)” technique, using the VLOC® device, a new autostatic suture available without necessity of making knots.
Material & Methods: In our department we used the new self-blocking reabsorbable suture V-LOCВ® on 14
patients undergoing to radical cistectomy and orthotopic ileal bladder replacement according to the VIP
technique. After cistectomy performed according to usual technique, we collected 55 cm. of ileum necessary for VIP reconstruction. We used the V-LOC 3/0 stitch for the entire reconstruction, making a one-layer
running suture on both the posterior and the anterior wall.
Results: The reconstruction of the orthotopic ileal neobladder using the self-blocking stitch has showed
effective and safe results. The procedure has been more simple and faster. Thanks to the autostatic little
wings along the stitch, it was possible to cut it at the end of the suture without making knots. The hydraulic
tests made at the end of reconstruction showed a perfect hydraulic closure of the ileal bladder. The results
were confirmed by a voiding cistography performed 12 days after surgery in all patients. So no early or
late suture dehiscences have been recorded.
Conclusions: The use of V-Loc device in orthotopic bladder replacement has proved to be safe and effective from a clinical point of view and, considering the economic aspects also, cost and time saving.
56
P011
Neoadjuvant chemotherapy for muscle invasive bladder cancer- Cisplatin vs Carboplatin a case
cohort study comparing the efficacy
Banerjee S., Rafiq M., Ndjavera W., Small M., Wade R.J., Kumar V.
Norfolk and Norwich University Hospital NHS, Dept. of Urology, Norwich, United Kingdom
Material & Methods: Data from two cohorts of patients who had Gem-Cis (Gemcitabine- Cisplatin, 3
cycles) and Gem-Carbo (Gemcitabine- Carboplatin 3 cycles) neoadjuvant chemotherapy regimens before
radical cystectomy were collected retrospectively using Med onc database, PACS, ICE and verified with
patient case notes. There had been no case selection for each regimen.
Results: A total of 33 patients were identified. 16 of them had Gem-Cis and 17 had Gem-Carbo neoadjuvant chemotherapy. Initial TURBT histology was compared with final cystectomy histology specimen. The
results were as follows.
Type of Chemo
Up staging
Same staging
Down staging
Total No of pts
Gem-Cis
2
3
11
16
Gem-Carb
7
6
4
17
11 patients had T0 cystectomy with 8 in Gem-Cis group and 3 in Gem-Carbo group. Gem-Cis group showed
superior response compared to Gem-Carbo group which was highly statistically significant (Fisher’s exact
t test P<0.014). Gem-Cis regimen showed better results with 50% (8/16) showing complete response and
69% (11/16) showing significant response as opposed to 23.5% complete response rate with Gem-Carbo
regimen. Toxicity was comparable between two regimens.
Conclusions: Gemcitabine-Cisplatin combination is a superior neoadjuvant chemotherapy regimen for
muscle invasive bladder cancer. We acknowledge the limitations of retrospective, non-randomised nature
of the study with small number of patients.
57
Unmoderated Posters
Introduction & Objectives: Neo-adjuvant chemotherapy offers 5% survival advantage in patients undergoing radical treatment for muscle invasive bladder cancer. Platinum based chemotherapy is considered to
be the gold standard. However the efficacies of cisplatin and carboplatin regimens have not been compared so far. In this study we compare the results of two platinum based chemotherapy regimens.
P012
Reduced overall survival and high progression rates for high risk, non-muscle invasive bladder
cancer in patients treated with maintenance BCG - 5 year outcomes
Smith H.E., Robson L., Thorpe A., Johnson M.
Freeman Hospital, Dept. of Urology, Newcastle Upon Tyne, United Kingdom
Unmoderated Posters
Introduction & Objectives: The standard treatment for high risk non-muscle invasive bladder cancer is
intravesical BCG with maintenance therapy. The goal of treatment is to reduce the rate of recurrence, reduce the risk of progression and improve survival. This 5 year retrospective study compares outcomes of
survival and recurrence of patients with T1 and Ta bladder cancer treated with BCG maintenance therapy.
Material & Methods: 110 consecutive patients received BCG therapy over an 18 month period. 91 sets
of notes were available for review with 5 years follow up after the initiation of BCG therapy. The intention at
outset was for all patients to receive a 6 week induction course of BCG followed by maintenance therapy
given at 3, 6, 12, 18, 24, 30 and 36 months.
Results: 91 patients were studied, 56 had T1 disease, 26 Ta and 9 CIS. Overall 5 year survival was 56%. In
T1 and Ta tumour groups the 5yr survival was 48% and 73% respectively. Overall recurrence was 41% with
89% of recurrences occurring in the first 12 months. Recurrence was more frequent in the Ta group 12/26
(46%) than the T1 group 20/56 (36%). Muscle invasive recurrences were seen more frequently in the T1
group 9/56 (16%) than the Ta group 3/26 (11.5%).
Conclusions: This study shows a similar overall recurrence rate to published studies. This study does
however highlight a higher frequency of muscle invasive recurrences and reduced survival in patients with
high risk T1 tumours who are commenced on BCG with the intention of completing a 3 year maintenance
regime. Patients and clinicians need to be aware of the risk of progression on BCG treatment and we feel
that the risks are high enough to justify a trial of radical surgical treatment versus BCG in patients with high
risk, non-muscle invasive bladder tumours.
58
P013
Outcomes of selective bladder preservation with neo-adjuvant chemotherapy in muscle invasive
transitional cell carcinoma (TCC)
Hafeez S., Huddart R.A.
Royal Marsden Hospital, Dept. of Academic Radiotherapy, Sutton, Surrey, United Kingdom
Material & Methods: Retrospective analysis of patients with T2-T4a N0 M0 bladder TCC treated between
January 2000 and June 2011. Patients received cisplatin based chemotherapy following transuretheral
resection of bladder tumour (TURBT), with repeat cystoscopy (with or without biopsy) performed to guide
subsequent management. Poor responders (4 patients) proceeded to surgery. We report on the outcome
of 68 individuals who received radiotherapy.
Results: 41 (60%) patients achieved complete response following chemotherapy (88% with stage T2). 20
(29%) patients achieved partial pathological response. In the remainder radiological assessment of response was made. Median time to disease progression was 12 months (range 3-49). 6 patients developed
invasive recurrence, 11 developed superficial recurrence and 10 patients developed metastatic disease.
After median follow-up of 32 months (range 7-116), 41 patients (60%) were alive with no disease, 22 (32%)
had died (19% from metastatic bladder cancer and 13% from other causes) and 3 (5%) patients were alive
with active disease (2 with localised and 1 with metastatic disease). 11 patients (16%) required cystectomy
(6 for superficial disease, 4 for invasive recurrence, and 1 for treatment related toxicity). Of those alive and
disease free 87% had an intact bladder. 83% had an intact bladder at last follow up or death.
Conclusions: Neo-adjuvant chemotherapy followed by radical radiotherapy allows bladder preservation in
over 80% of selected patients with survival rates comparable to contemporary surgical series.
59
Unmoderated Posters
Introduction & Objectives: In the absence of randomised comparisons between cystectomy and bladder sparing strategies, surgery remains the perceived gold standard of care for the treatment of muscle
invasive bladder cancer. Radiotherapy has been previously associated with high treatment failure, however
growing evidence suggests modern organ sparing approaches may have favourable outcome in appropriately selected patients. We investigate whether response to neo-adjuvant chemotherapy can guide selection
for bladder preservation and identify those patients likely to have greater success with radical radiotherapy
treatment.
P014
Dose-escalated bladder radiotherapy: Results of first dose cohort
Mcdonald F., Hafeez S., Lalondrelle S., Harris V., Taylor H., Warren-Oseni K., Hansen V.N., Jones K.,
Thompson A., Khoo V., Huddart R.
The Royal Marsden Hospital, Dept. of Radiotherapy, London, United Kingdom
Unmoderated Posters
Introduction & Objectives: The purpose of this prospective phase I study was to assess the safety of
dose escalation for localised muscle-invasive bladder carcinoma using image-guided adaptive radiotherapy
(RT) combined with reduced high-dose tumour volume.
Material & Methods: Radical RT was planned and delivered in 3 phases. Phase 1 was delivered to the
whole empty bladder (10Gy 5#). Bladder variation, assessed on daily imaging in phase 1, was used to
decide on a composite volume or plan of the day approach for the adaptive phase 3. Phase 2 was delivered
to a tumour boost volume in a partially full bladder (18Gy 9# if normal tissue dose-constraints were met,
otherwise 14Gy 7#). Subsequently, the adaptive phase 3 was delivered to the whole empty bladder (40Gy
20#). The primary endpoint was late RTOG toxicity.
Results: Twenty patients were recruited between May 2009 and April 2011. Fourteen (70%) patients met
the normal tissue constraints for reduced high-dose volume dose escalation. Nine patients (64%) had a
composite volume selected for the phase 3 adaptive technique and 5 (36%) were treated using optimal
plan of the day selection. At a median follow-up of 8 months, 10 of the dose escalated patients remain well
with no sign of cancer recurrence and 4 patients have died of unrelated causes (2 from cardiac and 2 from
pulmonary disease). There have been no grade ≥3 late toxicities. Three (21%) patients have experienced
G1-2 late genitourinary toxicity.
Conclusions: Implementation of image-guided adaptive RT techniques with reduced high-dose volume
strategy allow for a proportion of patients to achieve tumour dose-escalation within normal tissue constraints. Toxicity data to date suggest tolerability of 68Gy in the patients whose plans met normal tissue
dose constraints. Local disease control rates are promising. According to protocol recruitment has now
commenced at 70Gy dose level and follow-up continues.
60
P015
Transitional cell carcinoma (TCC) of the kidney pelvis and the ureter
Matveev V.B., Volkova M.I., Afonin S.V., Romanov V.A., Chemyaer V.
N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia
Material & Methods: A retrospective analysis of 95 consecutive patients with upper urinary tract TCC
treated at Cancer Center from 1987 to 2010 was performed. Urothelial tumors of the kidney pelvis were
diagnosed in 65 (68.4%), ureteral lesions – in 30 (31.6%) cases. Median age was 59.0±12.8 years. Male to
female ratio was 3:1. Category T1 occurred in 24 (25.3%), рТ2 – in 31 (32.6%), рТ3 – in 25 (25.3%), рТ4
– in 15 (15.8%); рN+ - in 24 (25.3%), bladder metastases – in 30 (31.6%) patients. Grade G1 was revealed
in 10 (10.5%), G2 – in 41 (43.2%), G3 – in 31 (32.6%), Gx – in 13 (13.7%) cases. All patients underwent
surgery. The surgical technique varied according to the diagnosis. Additional treatment was administered
in 17 (17.9%) cases (chemotherapy - 12 (12.6%), radiotherapy - 4 (4.2%) and chemoradiotherapy - 1 (1.1%)).
Neoadjuvant regimens were used in 3 (3.2%), postoperative – in 14 (14.8%) cases. Median follow-up was
49.2В±11.2 months.
Results: Complete remission was achieved only after complete tumor removal (67 (70.5%) of 95); conservative treatment was ineffective in all cases. Recurrences appeared in 28.4% (19/ 67) of cases a median of
19.9 (1-84) months after treatment. 5-year recurrence-free, cancer-specific and overall survival was 64.2%,
74.2% and 70.5% respectively. It was demonstrated adverse prognostic value of СЂT>T2, pN+ and bladder
metastases. Organ-sparing surgery, lymph node dissection (both in СЃN0 and СЃN+ patients), neoadjuvant
and adjuvant treatment did not influence survival. The only independent prognostic factor was completeness of surgery (СЂ<0.0001).
Conclusions: Surgery remains the most effective method of treatment in TCC of the kidney pelvis and the
ureter. The completeness of the tumor removal is the only favorable prognostic factor. Further investigations are needed to develop effective neoadjuvant and adjuvant options.
61
Unmoderated Posters
Introduction & Objectives: The main purpose of the study was to assess the results of treatment of TCC
of the kidney pelvis and the ureter.
P016
Complications of urinary diversion after radical cystoprostatectomy
Padilla-FernГЎndez B.1, Lorenzo-GГіmez M.F.1, AntГєnez-Plaza P.2, Virseda-RodrГ­guez A.J.1, MartГ­n-RodrГ­guez A.1,
Gil-Vicente A.1, Silva-AbuГ­n J.M.1
1
University Hospital of Salamanca, Dept. of Urology, Salamanca, Spain, 2University Hospital of Salamanca,
Dept. of Anatomical Pathology, Salamanca, Spain
Unmoderated Posters
Introduction & Objectives: Open cystoprostatectomy with extensive lymph node dissection is the preferred curative treatment in patients with muscle-invasive organ-confined bladder cancer or high grade T1
tumors failing intravesical therapy. We present the results of a retrospective study regarding the complications of several urinary diversion’s techniques performed in 85 radical cystoprostatectomies (RCP) in our
center.
Material & Methods: 85 male patients who underwent RCP between April2007-May2011 were included.
Age, urinary diversion performed, tumor stage, survival, neoadjuvant treatment and complication associated to urinary diversion are analysed with descriptive statistics, Student’s t-test, Fisher’s exact test;
p<0.05 was considered as significant.
Results: Median age 69.04y(49-83). Median follow-up in living patients 25.50months(9-56). Cancer-specific
mortality 18.82%. Table 1 shows diversion, complications and other observations in living patients.
Table 1.
Complications
%
OpenRCP+Ileal conduit(IC)+direct
ureteral reimplantation(n=22).
18.18%
Observations
Type
Right ureter estenosis(n=2).
Repeated urinary tract infections (UTI)
(n=2).
Neoadjuvant Chemotherapy(ChT)
(n=7).
Postoperative paralytic ileus(n=2).
Left nephrectomy after pyonefrosis,
right nephrostomy(n=1).
OpenRCP+IC+Wallace-I
anastomosis(n=4).
В В OpenRCP+IC+Wallace-II anastomosis (n=4).
50%
LaparoscopicRCP+IC+Wallace-II
anastomosis(n=3).
В Residual tumor at the psoas(n=1).
LapRCP+IC+Bricker+direct
ureteral reimplantation(n=1).
В Bilateral PTE with lung
infarction(n=1).
OpenRCP+Studer+direct ureteral
reimplantation(n=6).
16.66%
Percutaneous nephrostomy(n=2).
Neoadjuvant ChT(n=2).
Right nephrostomy after ureteral
estenosis and repeated UTI(n=1).
Left kidney’s ectasia
+liverMTX(n=1).
Neoadjuvant ChT(n=1).
Reoperation: DDneobladder/
abscess(n=1)
В OpenRCP+
ureterosigmoidostomy(n=4).
Intestinal obstruction(n=1).
OpenRCP+bilateral cutaneous
ureterostomy(n=3).
В В OpenRCP+cutaneous
transureteroureterostomy(n=4).
В В LapRCP+bilateral cutaneous
ureterostomy(n=1).
В В 62
В Leak at the anterior sigmoid wall, temporary
colostomy(n=1).
Only one complication was recorded in deceased patients: retroperitoneal urinoma after
OpenRCP+IC+direct ureteral reimplantation. OpenRCP+IC+direct ureteral reimplantation(n=7),
OpenRCP+IC+Wallace-I anastomosis(n=2), OpenRCP+IC+Wallace-II anastomosis(n=9), OpenRCP+cutaneous
transureteroureterostomy(n=12), OpenRCP+bilateral cutaneous ureterostomy(n=2) and
OpenRCP+ureterosigmoidostomy(n=1) were performed.
Unmoderated Posters
Conclusions: Open RCP with ileal conduit urinary diversion and direct ureteral reimplantation is the most
performed technique in our area with a complication rate of 18.18% including ureteral estenosis and UTI.
The Wallace-II anastomosis does not report any advantages with 50% complications. Studer’s urinary
diversion with direct reimplatantion shows the best results with 16.66% complications.
63
P018
Change of the indication of radical cystectomy: Age and treatment with Bacillus
Calmette-Guerin as determinant factors
Rodriguez Faba O., Palou J., Ochoa C., Gaya J.M., Parada R., Esquena S., Villavicencio H.
FundaciГі Puigvert, Dept. of Urology, Barcelona, Spain
Unmoderated Posters
Introduction & Objectives: Radical Cystectomy (RC) is the standard treatment in muscle invasive bladder
cancer. Elderly have been for years not considered for a RC, since it is associated to higher morbidity and
mortality. Additionally the evidence that high grade non-muscle invasive tumors (NMIBC) and CIS respond
to BCG, there has been a change of indication of RC for non-muscle invasive tumour (NMI) and considering
only in those patients with poor predictive factors. To analyse the evolution of RC indication in our series, in
periods of five years according to age and BCG treatment.
Material & Methods: We perfomed a retrospective study of our series of 1189 patients that underwent
RC between 1980 and 2005. We analyzed the evolution of the indication based on age (over or under
75 years), and the stage (NMIBC) of the RC related to the introduction of BCG as standart treatment. We
performed a descriptive study of both factors by chi square test.
Results: Between 1980-85, 96 (8.1%) patients underwent a RC, 1986-90: 228 (19.2%), 1991-95: 319
(26.8%), 1996-00: 339 (28.5%), 2001-2005: 207 (17.4%).
 ≥75 years
BCG
Pre-cystectomy
Indication
NMI
1980-85
0
1(1%)
36(37.5%)
1986-90
7(3.1%)
12(5.3%)
95(41.7%)
*1991-95
11(3.4%)
53(16.6%)
90(28.2%)
1996-00
33(9.7%)
52(15.3%)
101(29.8%)
2000-05
23(11.1%)
19(9.2%)
49(28.5%)
P value
<0.001
<0.001
<0.030
*Introduction of BCG
Conclusions: Over the years there is a significant increase in the indication of cystectomy in patients
over 75 years. The introduction of BCG has been a turning point in the indication of cystectomy. Since its
extensive use, the number of cystectomies for primary NMIBC tumour has significantly decreased.
64
P020
Laparoscopic radical cystectomy for bladder cancer in a non-academic center:
A single surgeons experience showing our results and learning curve
Van Aarle S.1, Van Dooren V.P.M.1, Brandenburg J.J.I.1, Sonneveld A.2, Fossion L.M.C.L.1
1
MГЎxima Medical Centre, Dept. of Urology, Veldhoven, The Netherlands, 2St. Anna Hospital, Dept. of
Urology, Geldrop, The Netherlands
Material & Methods: From September 2006 till July 2012, 68 patients underwent LRC for muscleinvasive bladder cancer or high risk superficial bladder cancer. Bilateral pelvic lymph node dissection occurred at the same time. A urinary derivation according Bricker was performed in 58 patients, a Hautmann
neobladder was constructed in 4 patients, an Indiana pouch in 2 patients. In all these patients a minilaparotomy was used as access (extracorporeal procedure). In 3 patients the Bricker urinary derivation was
constructed intracorporealy. One patient underwent a salvage LRC after radiation therapy. All procedures
were performed by the same surgeon. Peroperative parameters, complications and learning curve were
evaluated.
Results: Mean age was 69 years (41-86). 52 patients (76%) underwent LRC for muscle invasive bladder
cancer, 15 patients (22%) for recurrent high-grade or BCG-resistant non muscle invasive bladder cancer.
Median operating time was 350 min (260-780). Median peroperative blood loss was 500 ml (100-3300).
There was no conversion to open surgery. Pathological stage showed pTcis in 7 patients (10%), pT1 in
4 (6%), pT2 in 16 (23%), pT3 in 21 (31%) and pT4 in 10 patients (15%). In 10 patients (15%) there was no
residual tumor found in the specimen. Mean number of lymph nodes removed was 15 (3-36). Positive lymph
nodes were found in 17 patients (25%). Positive surgical margins were found in 8 patients (12%). Median
hospital stay was 13 days (5-147). Postoperative, 32 patients (47%) were transferred directly to general
ward, 20 (29%) went to Medium Care, 16 patients (24%) required Intensive Care. There were 11 complications (16%) requiring re-intervention under general anesthesia. One patient died of pneumosepsis.Regarding
learning curve we split the patients who had an extracoporeal urinary derivation according to Bricker (58
cases) into four groups. Mean operating time was reduced from 454 min in the first group to 324 min in the
fourth group. Blood loss was reduced from 870 ml to 467 ml. Regarding operating time, a downward trend
was seen throughout the all 58 cases.
Conclusions: Our experience with LRC shows promising results. Operating time and blood loss gradually
decreased following the number of cases. Learning curve still shows improvement after 30 cases, however
acceptable results can be obtained relatively quick if the surgeon has previous experience in laparoscopic
pelvic surgery.
65
Unmoderated Posters
Introduction & Objectives: Laparoscopic radical cystectomy (LRC) is a technically high demanding
procedure requiring advanced laparoscopic skills from the surgeon. The learning curve is longer compared
with the open procedure and is estimated to include about 30 cases. We report our results and learning
curve of 68 LRC’s performed by a single surgeon in a non-academic center.
P021
Radical cystectomy for bladder carcinoma: Results of a dutch high-volume center
Arends T.J.H., Bruins H.M., Pelkman M., Van Der Heijden A.G., Witjes J.A.
Radboud University Nijmegen Medical Centre, Dept. of Urology, Nijmegen, The Netherlands
Unmoderated Posters
Introduction & Objectives: The gold standard treatment of muscle invasive bladder cancer (MIBC) is
radical cystectomy (RC) and pelvic lymph node dissection (LND). Recent studies indicate that treatment
in a high-volume center (≥10 RC/year) gives better results than treatment in low-volume centers (<10 RC/
year). This retrospective study shows the results of a high-volume center during the last 12 years in The
Netherlands.
Material & Methods: Patients who underwent RC for bladder cancer between 1998 en 2009 were eligible
for this analysis. Clinicopathological characteristics of all subjects were collected using standardized retrospective medical record review. Median follow-up was 6.1 years. Recurrence free survival (RFS), overall
survival (OS) and peri-operative mortality (<30 days after RC) were the primary objectives.
Results: In total 351 patients are included and LND is performed in 305 patients (86.9%). Median number
of retrieved lymph nodes (LN) is 8. Peri-operative mortality occurs in 10 (2.8%) patients. Twenty (5.7%) patients have positive soft tissue margins; all with a ≥pT3 tumour. Of the 351 patients, a total of 181 (51.6%)
patients has an organ confined tumour (OC), 95 (27.1%) patients have extra vesical tumour (EV) extension
and 64 (18.2%) lymph node metastases (LN+). Data of 11 (3.1%) patients were missing. The 5-year RFS and
OS is 64% and 55%, respectively. The 5-year RFS in the OC, EV and LN+ subgroups is 78%, 55% and 28%
(p<0.0001, figure 1). On univariate analysis, presence of EV disease (p<0.0001), presence of LN positive
disease (p<0.0001) and soft tissue surgical margin status (p<0.0001) are associated with decreased RFS.
On multivariable analysis, presence of EV disease (RFS: HR 2.68 (1.60-4.51), p<0.0001) and presence of
LN positive disease (RFS: HR 3.61 (2.15-6.08), p=0.002) remains independently associated with decreased
RFS.
Conclusions: Peri-operative mortality and long-term survival in this study is comparable with large
reported series in the literature. The median number of nodes is lower compared to other series, in part
because this number is strongly influenced by several surgical en pathological factors. Tumour stage en
LN-status are the most important prognostic factors.
66
P022
Mainz Pouch II technique: The outcome and complications in 418 patients
Hadzi-Djokic J.1, Dzamic Z.2, Basic D.3, Pejcic T.2
1
Serbian Academy of Sciences and Arts, Dept. of Health Care, Belgrade, Serbia, 2Clinical Center of Serbia,
Dept. of Urology, Belgrade, Serbia, 3Clinical Center of Nis, Dept. of Urology, Nis, Serbia
Introduction & Objectives: To estimate the efficacy and safety of a modified Mainz Pouch II procedure.
Results: In the whole group, there were no intraoperative or early postoperative deaths. Early complications included prolonged bowel paralysis (11), acute pyelonephritis (32), unilateral ureterohydronephrosis
(21), bilateral ureterohydronephrosis (4) and incipient or transient renal failure (10). Late complications
included unilateral ureteric implantation-site stenosis (16) and bilateral ureteric implantation-site stenosis
(6).Total of 175 patients needed oral alkalizing medications and potassium supplementation because
of hyperchloremic metabolic acidosis. Continence rate was 98% (411 patients). The mean В± SD voiding
frequency was 4.4 В± 1.9 voids by day and 2.3 В± 0.7 at night.
Conclusions: The Mainz Pouch II technique is simple and reproducible surgical procedure, with acceptable
mortality, morbidity and continence rate and the quality of life. For selected cases, this technique is a good
alternative to other types of continent urinary diversion.
67
Unmoderated Posters
Material & Methods: From October 1994 to March 2011, 418 patients (287 men and 131 women,
mean age 58.2 years) underwent modified sigma- rectum pouch (Mainz Pouch II) procedure in 10 Serbian
hospitals. All operations were performed by single urological surgeon (J. H- Dj.). The median follow-up (317
patients) was 26 (1-102) months.
P023
Combination of low level laser therapy with mitomicin can lead to increase of recurrence free
survival in patients with non-muscle invasive bladder cancer
Alekseev B.Ya.1, Golovashchenko M.P.1, Nyushko K.M.1, Filonenko E.V.1, Andrianov A.N.1
Moscow Herzen Oncology Institute, Dept. of Oncourology, Moscow, Russia
1
Unmoderated Posters
Introduction & Objectives: Risk of recurrence in patients with non-muscle invasive bladder cancer
(NMIBC) is high. Development of techniques to prevent disease recurrence is actual. The aim of our study
was to assess results of adjuvant intravesical chemotherapy (IVC) with Mitomycin C (MMC) in combination
with low level laser therapy (LLLT) in patients with intermediate risk NMIBC.
Material & Methods: Since 2006 till 2010 years 106 patients with intermediate risk NMIBC were included
in the study. Experimental preclinical part of the study included 27 patients in whom concentrations of
MMC in tumor/normal tissue were assessed after standard IVC and IVC+LLLT using method of high effective liquid chromatography (HELC). Clinical part consisted from control (retrospective) arm which included
54 patients received TUR+6 courses of IVC. In experimental arm 25 patients received 6 courses IVC+LLLT.
Patients in all groups were comparable by prognostic risk factors using EORTC criteria. The patients with
carcinoma in situ were excluded from this study.
Results: Results of HELC have demonstrated, that median MMC concentration in normal tissue was
197mkg/g after IVC and 67mkg/g after IVC+LLLT. Median MMC concentration in tumor tissue was
101mkg/g (IVC) and 128mkg/g (IVC+LLLT) (p=0.0002). In control arm median follow-up was 39.5 months.
During this period recurrence was diagnosed in 33 (61%) patients, median recurrence free survival (RFS)
was 33 months. In investigative gpoup median follow-up was 32 months. Recurrences in this group was
diagnosed in 2 patients (8%) with median RFS of 32 months. Complications of combination therapy were
similar in control and experimental groups of patients (p=0.46).
Conclusions: Combination therapy increases concentration of MMC in tumor tissue and reduces recurrence rate for more than two year period of follow-up. IVC in combination with LLLT are perspective method
of treatment of patients with intermediate risk NMIBC, but further assessing of its efficacy is necessary.
68
P024
Impact of histopathological variant on the outcome of patients treated by radical cystectomy
for bladder cancer
Nadeem M., Ather M.H.
Aga Khan University, Dept. of Surgery, Karachi, Pakistan
Material & Methods: Patients treated with RC and PLND with urinary diversion between years 1988 to
2010, for muscle invasive bladder cancer (MIBC) were identified from hospital data base using medical
indexing coding system (ICD 9CM). 201 patients were identified of which 31 excluded either due to
inadequate follow up or missing data. Patients with follow up < 6 months and those with missing data were
excluded from the study. Demographics as well as clinico-pathological parameters including histopathological variant, Tumor stage and nodal status were reviewed. Multivariate analyses were used to evaluate
these parameters for overall survival (OS). Kaplan Meier estimate of the disease free survival was plotted
for survival estimate.
Results: Patients were predominantly male (84%) with mean age of 61+/- 13.1 years (27 to 87 years). The
mean follow up was 5.7 years (range 6 months to 11 years). Histological variant of UCC tumor was found
in 11% (19) patients, comparable to previously published data 10.4%. (9). The overall survival (OS) was 55%
with disease specific survival (DSS) being 66%. Patients with pathological stage T0 at cystectomy have
87% DSS compared to 60%, in patients with pT4 (p=0.705). The OS for node positive patients was 16%,
compared to 60% for node negative patients (p Histopathological variance showed significant impact on
morbidity and mortality (p=0.02 and 0.07 respectively). Kaplan Meier curve plotted for survival estimate
in different histopathological variants showed statistically significant difference (p= 0.02). Patients with
divergent histopathology of bladder tumor have poor survival in comparison to TCC.
Conclusions: RC and PLND is a standard of care for MIBC and high grade bladder tumor. Pathological
stage at RC and lymph node involvement are predictors for DSS and OS. Histopathological variance is an
independent risk factor determining the outcome in terms of both morbidity and mortality due to its
aggressive nature.
69
Unmoderated Posters
Introduction & Objectives: Bladder cancer is the second most common Genitourinary malignancy. Urothelial carcinoma (UCC) has a propensity for divergent differentiation i.e. squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelial cancer. Divergent
histopathology has different clinical course and survival outcome as shown in different case series and
case reports. The aim of this study is to compare the clinical outcome in different variants of bladder
tumor which is not previously reported in literature. To assess the impact of different histopathological
variants of bladder cancer on morbidity and mortality of patients undergoing radical cystectomy compared
to UCC, Squamous and adenocarcinoma.
P025
Considerations in the cancer specific survival assessment in radical cystectomy for bladder
cancer
Rodriguez Faba O., Palou J., Ochoa C., Parada R., Wong A., Gausa Ll., Villavicencio H.
FundaciГі Puigvert, Dept. of Urology, Barcelona, Spain
Unmoderated Posters
Introduction & Objectives: Pathological stage is a prognostic factor for survival in radical cystectomy
(RC). Several studies have reported up to 50% of clinical understage. Usually, the information of the cancerspecific survival (CSS) curves is related to the pathological report of the RC. To evaluate and compare the
CSS according to the clinical stage of TUR, the pathological stage at RC, and the higher stage evaluating
both clinical and pathological stage.
Material & Methods: We conducted a retrospective study of the clinic and pathological characteristics
of 888 patients treated with RC between 1978 and 2009. A reclassification of the stage for each patient
was made by comparing the clinical vs. pathological stage and selecting the higher of both. The analysis of
survival was performed using Kaplan-Meier, and comparison of stage by Cox regression model.
Results: The mean age was 62 (32-91) years, and 805 (90.7%) patients were men with a mean follow- up
of 41.3 months. In the stage reclassification, selecting the highest stage, 192 (21.7%) presented stage
Ta-1, Tis, and 696 (78.3%) T2-4. CSS according to the clinical stage, Ta-1/Tis patients had a CSS of 83%
and T2-4 of 75-50%; According to pathological stage was 90% and 60 -75% respectively. When the highest
stage was selected, CSS was 83% and 75-50%. Comparing the 3 groups: Although significant (p <0.05),
clinical stage does not discriminate accurately the differences between stages; Pathological stage differenciate the non-muscle invasive tumours of the muscle invasive (p <0.05); Finally, according to the highest
stage of both, the different stages are better discriminated (p =0.0001).
Conclusions: Clinical, pathological and clinical-pathological staging are all discriminative but the last one,
was better to separate significantly all the stages in bladder cancer related to cancer specific survival.
The stratification with both clinical (TURBT) and pathological (cystectomy specimen) is better than only
consider pathological stage.
70
P026
Prognosis of primary and progressive muscle-invasive urothelial bladder carcinoma – is there a
difference?
Ciudin A., Diaconu M.G., Molina A., Huguet J., Peri L., Ribal M.J., Alcaraz A.
Hospital Clinic Barcelona, Dept. of Urology, Barcelona, Spain
Material & Methods: We performed a retrospective review of 465 consecutive radical cystectomy performed in our center between 1991 and 2008. We studied 284 patients with primary MI bladder tumor and 87
bladder tumors with prrogressive MI bladder tumor. We excluded the cases with high-grade muscle-invasive
tumor with progression at less then 3 months, considering they could have been understaged during the
initial transurethral resection, and patients undergoing cystectomy for high-grade non-muscle-invasive
bladder tumor without response to BCG. We analyzed the pathological stages of the cystectomies in both
groups. We compared the 2 and 5 years cancer-specific survival in both groups globally and by pathological stages using the log rank of Kaplan-Meier survival curves. We performed multivariate analysis using the
Cox regression to exclude bias effects of age, gender and pathological stage.
Results: The mean age of the 371 MI bladder cancer patients was 64.3 years. The ratio male: female
ratio of 9:1. There were no significant differences between groups in age distribution, sex and pathological
stage. With a mean post-cystectomy follow-up of 30 months, cancer-specific survival at 2 and 5 years of
total patients was 67.7% and 52.3% respectively. Cancer-specific survival at 2 and 5 years for patients with
bladder cancer was 65.9% and 40.6% for progressive MI and 61.3% and 47.2% for the primary MI tumors
(no significant differences). When stratified by pathological stages we encountered significant differences
in survival at 2 and 5 years for patients with T4 tumor stage (57% for progressive MI tumors vs 32% for
primary MI tumors, p = 0,001).
Conclusions: At global level we did not observe differences in the final outcome of patients with muscleinvasive bladder cancer with primary and/or progressive muscle-invasive tumor. On the other hand in
patients with T4 tumor stage there was a higher survival rate in those who have progressive tumors.
71
Unmoderated Posters
Introduction & Objectives: Up to 20-40% of urothelial carcinomas are muscle-invasive (MI), either at
initial diagnosis (85%) or progressing from a non-muscle-invasive tumor (15%). There is controversy about
whether these two different forms of presentation of MI tumors have implications in the final prognosis
of the patients. Our objectives were to assess in our series of radical cystectomy the characteristics and
evolution of patients with primary and progressive MI bladder cancer.
P028
T4 bladder tumour affecting the prostate. Prognostic differences depending on the bladder
tumour evolution: Primary versus progressive tumours
Ciudin A., Huguet J., Peri L., Ribal M.J., Alcaraz A.
Hospital Clinic Barcelona, Dept. of Urology, Barcelona, Spain
Unmoderated Posters
Introduction & Objectives: Cystectomy is the standard treatment for muscle-invasive urothelial tumors.
An involvement of the prostate was described in 15-48% of the cystectomies for urothelial carcinoma.
This condition occurs in two ways: - by transmural extent of the tumor from the bladder into the prostatic
stroma;- by arising from the prostatic urethra, where according to the depth of invasion will affect the
mucosa, ducts or stroma. Our objective was to assess whether prostatic stromal involvement occurs
differently between primary (de novo muscle invasive) and progressive (muscle invasive with a history of
non-muscle-invasive) tumours and also to assess if this has any impact in patients’ prognosis.
Material & Methods: We performed a retrospective analysis of our cystectomy database. We reviewed
301 patients treated between January 2000 and December 2008. Inclusion criteria: 1) pT4a bladder
tumors affecting the prostate; 2) only stromal involvement of the prostate was accepted, discarding the
patients with involvement of the mucosa or prostatic ducts. We evaluated: prior history of non muscle
invasive bladder tumour, pathological stage, treatment and outcome of these patients.
Results: Of 301 patients undergoing cystectomy we identified 49 (16.27%) with tumors involving the
prostatic stroma. Of these, 29 were primary invasive tumors and 20 progressive tumors. In almost all of
the cases with primary invasive tumor (28 out of 29 cases - 96.6%), the involvement of the prostate was by
means of extramural extension from the bladder. In one case (3.4%) the prostate was involved by extension
through the prostatic urethra. In most of the cases with progressive invasive tumor (13 out of 20 patients
- 65%), prostatic involvement had its origin in the prostatic urethra. In the other 7 cases (35%) there was a
transmural infiltration from the bladder. More patients had positive lymph nodes in primary invasive tumors
(48.27% - 14 patients versus 25% - 5 patients, p = 0.09). The 2 years and 5 years overall survival was
lower in the group of primary invasive tumors when compared to progressive invasive tumors (two years:
35% versus 51% p = 0,01), (five years: 19% versus 31%, p=0.03). Patients with stromal involvement by
means of transmural invasion from the bladder had a lower 2 years and 5 years overall survival than
patients with stromal involvement by prostatic urethra (32.1% versus 53.7%, p = 0.03) (17% versus 33%,
p=0.01).
Conclusions: Stromal involvement of the prostate with urethral origin is much more frecuently associated with progressive tumors. Transmural involvement of the prostate is associated with primary invasive
tumours and with poorer survival.
72
P029
Charlson comorbidity index: Impact of comorbidity in predicting 90 day survival of patients
treated with radical cystectomy
Ather M.H., Haroon N.
Aga Khan University, Dept. of Surgery, Karachi, Pakistan
Material & Methods: This retrospective cohort study was conducted at a university hospital. Patients,
who had undergone radical cystectomy for urothelial cancer during the period 1989 to 2012, were included. The charts’ were reviewed for details of clinical, pathological and radiological evaluation including pre,
peri and postoperative work up to 3 months following surgery. Charlson’s index and 90 day mortality was
assessed. Logistic regression was used to determine association between CCI, co morbidity index and 90
day mortality.
Results: Total 175 patients were found eligible and reviewed. Baseline variables were comparable among
the three categories of CCI. Morbidity was not significantly different; however, mortality was significantly
higher in CCI group 3. On multivariable logistic regression, the odds of 90-day mortality were 13 times
higher in CCI 3 (13.6 % with 95% confidence interval 3.3%, 56.1%).
Conclusions: Charlson comorbidity index (≥ 4) is a strong predictor of 90-day postoperative mortality in
patients undergoing radical cystectomy.
73
Unmoderated Posters
Introduction & Objectives: Radical cystectomy (RC) is the standard of care for muscle invasive and
high grade non muscle invasive bladder cancer. It is often performed on elderly patients with significant
co morbidities. RC is associated with significant peri operative morbidity and also mortality. Factors
responsible for high complication of RC includes complex nature of surgery, bowel related complications,
age and comorbidities. One of the ways of objective assessing and quantifying co morbidites is Charlson's
co morbidity index. To evaluate the impact of Charlson’s co morbidity index (CCI) on 90-day mortality in
patients undergoing radical cystectomy for urothelial cancer (UCC) at a tertiary care hospital.
P030
An ERk-inhibitor AZD6244 (ARRY-142886) enhances the anti-tumor activitiy of sorafenib
therapy in a xenograft model of human renal cell carcinoma (RCC)
Yuen J.1, Sim Y.1, Huynh H.2
1
Singapore General Hospital, Dept. of Urology, Singapore, Singapore, 2National Cancer Centre, Cellular &
Molecular Research, Singapore, Singapore
Unmoderated Posters
Introduction & Objectives: Sorafenib, a multikinase inhibitor is currently used as monotherapy for advanced RCC. However, adverse effects associated with its use have proven problematic in some patients. In
this study, we aim to examine the antitumor and antiangiogenic activities of low dose sorafenib in combination with MEK inhibitor, AZD6244 (sorafenib/AZD6244) in a preclinical model of RCC.
Material & Methods: Primary RCC08-0910 and RCC 786-0 cells as well as patient-derived RCC models
were used to study the antitumor and antiangiogenic activities of sorafenib/AZD6244. Changes of biomarkers relevant to VEGFR, Raf/MEK/ERK and mTOR pathways and cell cycle were determined by western
immunoblotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry.
Results: Treatment of RCC 786-0 cells with sorafenib/AZD6244 resulted in G1 cell cycle arrest and
blockade of serum-induced cell migration. Sorafenib/AZD6244 induced apoptosis in primary RCC 08-0910
at low concentrations. Sorafenib as monotherapy induced significant tumor growth inhibition which was
associated with modest reduction in p-ERK1/2. AZD6244 alone inhibited p-ERK1/2 but had modest or no
significant anti-tumor activity. Addition of AZD6244 to sorafenib significantly augmented the antitumor
activity of sorafenib and allowed dose reduction of sorafenib without compromising its anti-tumor activity.
Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-ОІ, Akt, ERK,
p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib/AZD6244 also caused upregulation of p27, Bad and
Bim but downregulation of survivin and cyclin B1. These resulted in a reduction in cellular proliferation and
the induction of tumor cell apoptosis.
Conclusions: Our findings showed that AZD6244 and sorafenib complement each other to inhibit the
growth of patient-derived RCC xenografts. This study provides a compelling rationale for clinical investigation of low-dose sorafenib in combination with AZD6244 in patients with advanced RCC, especially in
patients who cannot tolerate full dose sorafenib due to adverse events.
74
P031
Prognostic value of plasma levels of vascular endothelial growth factor (VEGF) and its
receptors (VEGFR) in metastatic renal cell carcinoma (mRCC) patients treated with
antiangiogenic therapies
Peters M.V.1, Shevchenko V.E.2, Matveev V.B.1, Volkova M.I.1
1
N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia, 2Moscow Medical Academy, Inst. of Molecular Medicine, Moscow, Russia
Material & Methods: Plasma samples were collected from 22 mRCC patients before and during
antiangiogenic therapies. Plasma hVEGF, hVEGFR2, hVEGFR3 levels were determined in duplicate using a
Quantiglo chemiluminescent ELISA kit. Statistical analyses were performed to determine the correlation
between plasma hVEGF, hVEGFR2, hVEGFR3 levels (before, during treatment and % of an increase) and
treatment results (progression rate, time to progression, time of overall survival).
Results: Median hVEGF levels before and during treatment were 380.5 (69-3183) pg/ml and 632.3 (533412.5) pg/ml (median % of an increase=-0.4% (-95-361.0%)); hVEGFR2 – 5407.0 (0-23673) pg/ml and
5899 (2113-51660) pg/ml (median % of an increase=-5.7% (-64.5-124.5%)); hVEGFR3 – 106268 (32017364342) pg/ml and 82563.9 (11257- 604565) pg/ml (median % of an increase=-22.8% (-84.6-65.9%)) respectively. As a continuous variable, pretreatment plasma hVEGFR3 levels inversely correlated with the time
to progression (p=0.039). An increase of hVEGFR3 levels after starting of antiangiogenic therapies directly
correlated with the time of overall survival (p=0.012). Concentrations and dynamics of levels of hVEGF and
hVEGFR2 did not influence results of antiangiogenic treatment in mRCC patients.
Conclusions: Although these data are exploratory and need to be confirmed in an independent data set,
they suggest that hVEGFR3 may have clinical significance in patients with mRCC treated with antiangiogenic therapies.
75
Unmoderated Posters
Introduction & Objectives: The main purpose of the study was to determine whether serum levels of
VEGF and its receptors (VEGF R2 and VEGF R3) had prognostic significance in mRCC patients treated with
antiangiogenic therapies.
P032
Gene expression profiling for high risk progressive non-muscle invasive urothelial cell
carcinoma of the bladder
Van Der Heijden A.G.1, Mengual L.2, Ribal M.J.2, Alcaraz A.2, Lozano J.J.3, Fernandez P.L.4, Schalken J.A.1,
Witjes J.A.1
Radboud University Nijmegen Medical Centre, Dept. of Urology, Nijmegen, The Netherlands, 2 Hospital
Clinic; IDIBAPS; Universitat De Barcelona, Dept. of Urology, Barcelona, Spain, 3CIBERehd. Plataforma De
BioinformГЎtica. Centro De InvestigaciГіn BiomГ©dica En Red De Enfermedades, Dept. of Bioinformatics,
Barcelona, Spain, 4 Hospital Clinic; IDIBAPS; Universitat De Barcelona, Dept. of Pathology, Barcelona, Spain
Unmoderated Posters
1
Introduction & Objectives: Up to 15% of all patients with non-muscle invasive bladder cancer (NMIBC)
show progression to muscle invasive bladder cancer (MIBC). Conventional histopathological evaluation is
inadequate to accurately predict this progression and the cancer-specific survival is severely reduced when
progression occurs. Therefore, especially patients at high risk for progression deserve careful attention. In
this study a gene expression signature model to discriminate progressive from non-progressive NMIBC was
composed.
Material & Methods: Thirty patients, 15 recurrent non-progressive high risk NMIBC patients with at
least 2 years of follow up and 15 recurrent progressive high risk NMIBC patients (with at least six months
between the transurethral resection showing NMIBC and the progression to MIBC), were included in this
analysis. After marking the high risk tumours by the pathologist a macro dissection of the urothelial cell
carcinoma in the paraffin block took place and RNA was isolated from the formalin-fixed, paraffin-embedded (FFPE) tissue using a commercially available kit. Total RNA was quantified by spectrophotometric
analysis at 260 nm. Gene expression analysis was performed using the Whole-Genome Gene Expression
DASL HT Assay according manufacturer’s instructions. A list of the most statistical significant regulated
genes was computed using LIMMA R-package. A gene expression signature to distinguish non progressive
from progressive NMIBC were obtained using PAM.
Results: In total 887 transcripts were found significantly (p<0.05) differentially expressed between
recurrent non-progressive and progressive high risk NMIBC. After PAM analysis we found an eighty gene
expression model that was able to distinguish both groups with 100 % sensitivity and specificity. The gene
signature will be validated in an independent cohort of patients using the Fluidigm Biomark real time PCR
system.
Conclusions: This analysis shows that gene expression patterns from FFPE samples are able to
discriminate recurrent non-progressive from progressive high risk NMIBC. The discrimination of these
patient groups shall improve patient treatment and outcome.
76
P033
Differences in the clinical profile between clear-cell and papillary type I and II renal carcinomas
in a sample of 315 patients
Padilla-Fernandez B.1, Lorenzo-Gomez M.F.1, Antunez-Plaza P.2, Garcia-Cenador M.B.3, Miron-Canelo J.A.4,
Martin-Rodriguez A.1, Gil-Vicente A.1, Silva-Abuin J.M.1, Instituto De InvestigaciГіn BiomГ©dica De Salamanca.
1
Complejo Asistencial Universitario De Salamanca, Dept. of Urology, Salamanca, Spain, 2Complejo Asistencial Universitario De Salamanca, Dept. of Pathological Anatomy, Salamanca, Spain, 3Universidad De
Salamanca, Dept. of Surgery, Salamanca, Spain, 4Universidad De Salamanca, Dept. of Preventive Medicine
and Public Health, Salamanca, Spain
Material & Methods: A retrospective analysis studying the clinical profile (gender, age, risk factors, tumoral stage and survival) of patients with diagnosis of CCRC, PIRC and PIIRC in our health area from January
2005 until December 2011 was performed. Descriptive statistics, Student’s t-test,Fischer’s exact test,
Chi-Square and Kaplan-Meier survival curves were used. p<0.05 was accepted as significant.
Results: 249 patients (70,74%) were diagnosed with CCRC (Group A), 12 (3.41%) with PIRC (Group B) and
54 (15.34%) with PIIRC (Group C). Other tumor types diagnosed were chromophobe carcinoma (3.98%),
papillary clear-cell carcinoma (0.7%), Xp11.2 translocation carcinoma (0.28%), tubule-papillary carcinoma
(0.85%), carcinoma of the collecting ducts of Bellini (0.85%), mucinous tubular and spindle cell carcinoma
(0.57%), multicystical (0.85%), unclassified carcinomas (0.85% sarcoma and 1.42% pleomorphic) and
oncocytoma (5.11%). Between groups there were no clinical relevant differences regarding age (69.32,
71.83 and 66.25 respectively) or gender distribution (26, 20 and 30% of female patients respectively).
Hematuria was more common (p<0.0023) in CCRC than in PIRC and PIIRC. HTN and smoking habit were
more frequent in CCRC (p>0.0036) than in PIRC and PIIRC. The 3 groups were similar when analysing TNM
stage (p=0.9276) and histological grade (p=0.2196) after surgery. The survival rate was inferior in the
PIIRC group (p<0.00036).
Conclusions: We have found differences in the risk factors associated with the different histological types
of renal carcinoma. CCRC appears more often with macroscopic hematuria, which is less common in
PIRC and PIIRC, and it has a closer relationship with smoking habit and HTN. Wider studies are necessary
in order to clear the meaning of the relationship between smoking habit and HTN in each of the different
histopathological renal carcinoma’s types.
77
Unmoderated Posters
Introduction & Objectives: To investigate the differences in the clinical profile of patients with diagnosis
of clear-cell (CCRC) and papillary type I (PIRC) and II (PIIRC) renal carcinoma in a sample of 315 patients.
P034
Preoperative understaging of renal cell carcinoma with multidetector CT
Halawa GonzГЎlez O.B.1, Galvez GarcГ­a C.2, Balig Fawwaz B.F.1, Del Rosario Rodriguez V.1, Fumero Gorrin C.1,
FalcГіn Barroso J.1, Portero Navarro J.2, Monllor Gisbert J.1
Hospital Universitario Nuestra SeГ±ora De Candelaria, Dept. of Urology, Santa Cruz De Tenerife, Spain,
Hospital Universitario Nuestra SeГ±ora De Candelaria, Dept. of Radiology, Santa Cruz De Tenerife, Spain
1
Unmoderated Posters
2
Introduction & Objectives: Renal cell carcinoma (RCC) represents 2-3% of all cancers. RCC is the
commonest solid lesion within the kidney and accounts for approximately 90% of all kidney malignancies.
The evolution of CT technology and the introduction of multidetector computed tomography (MDCT) have
provided higher spatial resolution and faster acquisition. Three-dimensional reformatting techniques enable
easy performance of multiplanar reconstructions, which improves the staging capabilities for RCC. Tumor
stage is the most important factor affecting the prognosis and survival of patients, and has an important
bearing on planning treatment. The purpose of the present study was to evaluate the diagnostic accuracy
of MDCT for preoperative staging of RCC using the 2009 TNM (tumor, node, metastasis) classification.
Material & Methods: We conducted a retrospective review of MDCT in 25 consecutive patients with RCC
performed for tumor staging before radical nephrectomy. The scanning protocol of MDCT consisted of
unenhanced and biphasic contrast-enhanced scans during corticomedullary and nephrographic phases.
MDCT and surgical-histopathologic staging were performed using the 2009 TNM staging system. The
results of MDCT were compared with the histopathological results.
Results: Consistency between MDCT and histopathologic staging was excellent for T1 (100%) and T2
staging (86%) and fair for T3 stage (44%) with an overall accuracy of 80% and 20% of understaging.
Conclusions: MDCT results are indeterminate investigating venous involvement if there is a badly defined
extension of locally advance masses and inferior vena cava tumour thrombus.
78
P035
Non-cutaneous de novo malignancy following kidney and liver transplantation: A comparison in
a single centre cohort of 2941 recipients
Branco F.1, Cavadas V.1, OsГіrio L.1, Braga I.2, Cordeiro E.3, Silva- Ramos M.1, Rocha A.4, Martins L.2,
Silva D.5, Silva J.D.5, Daniel J.5, Fraga A.1
Centro Hospitalar Do Porto, Dept. of Urology, Oporto, Portugal, 2Centro Hospitalar do Porto, Dept. of
Nephrology, Oporto, Portugal, 3AMC Hospital, Dept. of Urology, Amsterdam, The Netherlands, 4Centro
Hospitalar Do Porto, Dept. of General Surgery, Oporto, Portugal
1
Material & Methods: Renal and hepatic transplantation were initiated in January 1983 and May 1995,
respectively, in our hospital. Until August 2011, 2016 kidney and 925 liver transplants were performed.
Mean age at transplantation was 44 and 43 years for kidney and liver transplantation, respectively; 61% of
kidney and 58% of liver recipients were male. Overall allograft survival at 5 and 10 years was 80 and 66%
for kidney and 60 and 48% for liver, respectively. Our prospective database was surveyed to retrieve data
for all patients who developed non-cutaneous de novo tumors. Kaplan-Meier survival was calculated for
both kidney and liver recipients.
Results: Eighty-four and 15 non-cutaneous de novo tumors were detected respectively in 2016 kidney
(4.2%) and 925 liver transplant recipients (1.6%). Mean age at diagnosis was 55 years in both groups, after
a mean follow-up until diagnosis of 142 and 58 months for renal and hepatic transplanted patients, respectively. The table depicts the type of neoplasms diagnosed in each group. Mean 1 and 5-year cancer-specific survival after diagnosis was 85 and 70% for kidney and 20 and 7% for liver recipients, respectively.
В Kidney recipients
Liver recipients
Total
Death
Total
Death
Gastrointestinal
16
8
6
6
Gynecological
21
3
1
1
Hematological
14
6
1
1
Miscellaneous
18
2
6
6
Urological
15
4
1
1
Total
84
23
15
15
Table 1. Non-cutaneous de novo malignancies in kidney and liver recipients.
Conclusions: In our cohort, non-cutaneous de novo tumors, despite being less frequent, are more aggressive in liver transplant recipients. Risk factors contributing for hepatic failure and the need of transplantation may be more important than immunosuppression in the development of de novo malignancy in this
group of patients, when compared to kidney recipients.
79
Unmoderated Posters
Introduction & Objectives: De novo malignancy after kidney and liver transplantation has become a
major concern in recent years, being one of the most important causes of death in these patients. Herein
we compare non-cutaneous de novo tumors arising in a single-centre cohort of renal and hepatic transplant
recipients.
P036
Bisphosphonates (Bis) combined with sunitinib (Su) may improve the response rate (RR),
progression free survival (PFS) and overall survival (OS) of patients (pts) with bone metastases
(mets) from renal cell carcinoma (RCC)
Keizman D.1, Ish-Shalom M.1, Maimon N.1, Gottfried M.1, Peer A.2, Neumann A.2, Hayat H.3, Boursi B.4, Kovel
S.5, Sella A.5, Pili R.6, Hammers H.7, Sinibaldi V.7, Eisenberger M.7, Berger R.4, Carducci M.7
Unmoderated Posters
1
Meir Medical Center, Institute of Oncology, Kfar Saba, Israel, 2Rambam Medical Center, Department of
Oncology, Haifa, Israel, 3Wolfson Medical Center, Department of Oncology, Holon, Israel, 4Sheba Medical
Center, Department of Oncology, Tel Hashomer, Israel, 5Asaf Harofe Medical Center, Department of Oncology, Zerifin, Israel, 6Roswell Park, Cancer Institute, Buffalo, United States of America, 7Johns Hopkins,
Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America
Introduction & Objectives: Bis are used to prevent skeletal events of bone mets, and may exhibit anti
tumor effects. We aimed to evaluate whether Bis can bring a RR, PFS, and OS benefit to pts with bone mets
from RCC that are treated with Su.
Material & Methods: We performed an international multicenter retrospective study of pts with bone
mets from RCC who were treated with Su. Pts were divided into Bis users (group 1) and nonusers (group
2). The effect of Bis on RR, PFS and OS, was tested with adjustment for known prognostic factors using a
chisquare test from contingency table and partial likelihood test from Cox regression model.
Results: Between 2004-2011, 244 pts with metastatic RCC were treated with Su. 92 pts had bone mets,
41 group 1 and 51 group 2. The groups were balanced regarding the following known prognostic factors:
past nephrectomy, clear cell vs non clear cell histology, initial diagnosis to sunitinib treatment (tx) time,
presence of ≥ 2 mets sites, presence of lung/liver mets, ECOG performance status, anemia, calcium level
> 10 mg/dL, elevated alkaline phosphatase (AP), pre-tx neutrophil to lymphocyte ratio (NLR) >3, sunitinib
induced HTN, and the use of angiotensin system inhibitors. They were also balanced with regard to past
cytokines/targeted tx, and mean sunitinib dose/cycle. Objective response was partial response/stable
disease 85% (n=35) vs 71% (n=36), and progressive disease 15% (n=6) vs 29% (n=15) (OR 3.287, p=0.07)
in group 1 vs 2 respectively. Median PFS was 15 vs 5 months (HR 0.433, p=0.035), and median OS not
reached with a median folloup time of 43 mos vs 12 months (HR 0.398, p=0.003), in favor of group 1. In
multivariate analysis of the entire pt cohort (n=92), factors associated with PFS were Bis use (HR=0.433,
p=0.035), pre-tx NLR ≤3 (HR 0.405, p=0.016), and elevated AP (HR=3.63, p=0.012). Factors associated
with OS were Bis use (HR 0.32, p=0.003), elevated AP (HR 3.18, p=0.002), and Su induced HTN (HR 0.193,
p< 0.001).
Conclusions: Bis may improve the outcome of Su tx in RCC with bone mets. This should be investigated
prospectively, and if validated applied in clinical practice and clinical trials.
80
P037
Surgical management of Renal Cell Carcinoma (RCC) with venous invasion in patients with
distant metastases
Davydov M.I., Matveev V.B., Figurin K.M., Volkova M.I., Chernyaev V.A., Kimov K.A.V.
N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia
Material & Methods: 127 consecutive patients with RCC T3a-bN0-2M1 with venous involvement were
treated surgically at our institution between 1984 and 2010. Median age was 57В±11.2 years, male to
female ratio - 1.5. Right kidney was involved in 60.2%, left - in 36.6%, both – in 3.1% of cases. The tumor
thrombus was confined to the renal vein in 48 (37.8%), extended to the perirenal IVC – in 13 (10.2%),
subhepatic IVC – in 24 (18.9%), retrohepatic IVC – in 18 (14.2%), intrapericardial IVC – in 10 (7.9%) and the
right atrium in 14 (11.0%) of 127 cases. Distant metastasis were present in all patients (solitary – 28.3%,
multiple – 71.7%). One metastatic site occurred in 58.4%, >1 – in 41.6% of cases. 67.5% of patients were
diagnosed with pulmonary, 14.3% - adrenal gland, 7.8% - bone, 10.4% - other metastases. All patients
underwent nephrectomy and thrombectomy, 14 (11.0%) - resection of solitary metastasis (simultaneous – 7
(5.5%)). Histology showed lymph node metastasis in 54 (42.6%) patients (N1 – 11 (8.7%), N2 – 43 (33.9%)).
The perinephric fat invasion was in 54 (42.6%) cases. 118 (92.9%) patients were considered for conservative treatment postoperatively. Median follow-up was 15 (3-132) months.
Results: Complete removal of the kidney and tumor thrombus was performed in 111 (87.4%), radical
metastasectomy – in 11 (8.7%) cases. Serious complications and mortality rates were 26.0% and 7.9%
respectively. The overall 5- and 10-year survival of 127 patients was 34.9% and 13.1%, cancer specific –
40.9% and 15.3% respectively. In the univariate analysis survival was affected by perinephric fat invasion
(p=0.008), pN+ (p<0.0001), >1 metastatic sites (p=0.002), complete removal of all lesions (p=0.080).
Category pN+ (СЂ=0.050) and number of metastatic sites (СЂ=0.022) were independently associated with
cancer-specific survival. The groups of patients with or without adverse factors (pN+ and/or >1 metastatic sites) had distinctly different prognosis (5-year cancer specific survival - 55.3% vs 0.0% respectively,
p<0.0001).
Conclusions: Surgery allows to escape fatal complications of tumor venous invasion in RCC patients.
Cytoreductive nephrectomy and thrombectomy is relatively safe and effective in selected cases of
metastatic RCC. Surgery is justified in patients without regional metastases.
81
Unmoderated Posters
Introduction & Objectives: To assess the results of surgical management of RCC with venous invasion in
patients with distant metastases.
P038
Laparoscopic radical nephrectomy: Techniques, results and oncological outcome in 150
consecutive cases
Halawa GonzГЎlez O.B., FalcГіn Barroso J., Rodriguez Talavera J., Amir Nicolau B.F., Del Rosario Rodriguez V.,
Fumero Gorrin C., Monllor Gisbert J.
Hospital Universitario Nuetra SeГ±ora De Candelaria, Dept. of Urology, Santa Cruz De Tenerife, Spain
Unmoderated Posters
Introduction & Objectives: The laparoscopic technique combines the benefits of minimal invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach
with intact specimen removal has become the standard technique for radical nephrectomies. We report the
indications, techniques and oncological outcome in a single center experience.
Material & Methods: Between 2007 and 2011 we performed laparoscopic radical nephrectomies for in
150 patients, 111 oncological and 39 non oncological. Their initial staging, complications and postoperative course were evaluated.
Results: 145 procedures out of 150 were successful. In five cases (7.5%) conversion to open surgery was
necessary due to bleeding. Intraoperative complications could be managed laparoscopically. In one case
(1.5%) postoperative bleeding lead to open revision for hemostasis. The mean surgical time was 220 min.
In the oncological group, 88 patients (80%) were renal cell carcinoma and 20 (17%) upper urinary tract
urothelial cell carcinoma. The main indication for non oncological laparoscopic radical nephrectomy was
benign non-functioning kidney (33 patients). The follow-up was between 3 and 60 months.
Conclusions: Laparoscopic radical nephrectomy has clear advantages compared to the traditional
surgery, especially about less morbidity, less blood loss, shorter hospitalization, with an oncologic
outcome absolutely comparable to the laparotomic procedure.
82
P039
Pulmonary metastases (PM) of renal cell carcinoma (RCC): Results of surgical resection
Matveev V.B.1, Volkova M.I.1, Polotskiy B.E.2, Turkin I.N.2
1
N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia, 2N.N. Blokhin Cancer Center, Dept. of
Thoracic Surgery, Moscow, Russia
Material & Methods: From 1985 to 2010, 60 consecutive patients underwent surgery for PM of RCC (in
view of cure – 55 (91.6%)). Median age was 55 (31-70) years. PM were diagnosed synchronously with the
kidney tumor in 20 (33.3 %), metachronously – in 40 (66.7 %) patients. Unilateral lesions occurred in 53
(88.3 %), bilateral in 7 (11.7 %) cases. 41 (68.3 %), patients had solitary, 19 (31.7 %) - multiple PM. Lung
lesions less than 2 cm were revealed in 69 % of cases. All 60 patients underwent surgery for PM. Complete
PM removal was performed in 50 (83.3 %) of 60 cases. The primary tumor was removed in 56 (93.3 %)
patients. Median follow-up was 20 (3-155) months.
Results: Major complications and mortality rates were 6.6% and 0% respectively. Histology proved PM of
RCC in all cases. Metastases in mediastinal lymph nodes were found in 3 (5%) patients. 5 - and 10-yearoverall, specific and relapse-free survival was 36.3% and 19.1%, 38.9% and 27.2%, 20.4% and 11.7%
respectively. In the univariate analysis specific survival was affected by bilaterial pulmonary lesions,
metastases in mediastinal lymph nodes and incomplete removal of PM. Radical surgery was the only factor
independently associated with cancer-specific survival in multivariate analysis.
Conclusions: Surgical resection of PM of RCC is safe and effective procedure. The best candidates for
surgical intervention are patients with limited intrathoracic extension of the tumor.
83
Unmoderated Posters
Introduction & Objectives: The main purpose of the study was to assess the results of surgical management of pulmonary metastases of RCC.
P040
Tivozanib pharmacokinetic (PK)/pharmacodynamic (PD) analysis of blood pressure (BP) and
soluble vascular endothelial growth factor receptor 2 (sVEGFR2) in patients with advanced renal
cell carcinoma (RCC)
Nosov D.A.1, Motzer R.J.2, Loewy J.3, Hodge L.3, Esteves B.4, Berkenblit A.4, Yin W.4, Dykstra K.3,
Hutson T.E.5, Cotreau M.M.4
N.N. Blokhin Cancer Research Center, Under The Russian Academy of Medical Sciences, Dept. of Clinical
Pharmacology & Chemotherapy, Moscow, Russia, 2Memorial Sloan-Kettering Cancer Center, Dept. of
Oncology, New York, United States of America, 3QPharmetra, Dept. of Oncology, Andover, United States of
America, 4AVEO Oncology, Dept. of Oncology, Cambridge, United States of America, 5Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dept. of Oncology, Dallas, United States of America
Unmoderated Posters
1
Introduction & Objectives: Tivozanib is a potent, selective, long half-life tyrosine kinase inhibitor of VEGF
receptors (VEGFRs) 1, 2, and 3, demonstrating activity against advanced RCC in Phase II–III trials. This
analysis explored the relationship between tivozanib PK and BP, as hypertension is a mechanism-based
adverse event and a potential surrogate of response. The relationship between exposure and sVEGFR2 also
was explored.
Material & Methods: PK, BP, and sVEGRF2 data from tivozanib-treated RCC patients from a Phase II
(n=21) and a Phase III (n=259) study were pooled; patients were treated with tivozanib 1.5 mg daily for 3
weeks followed by a 1 week rest period (4-week treatment cycle) in each study. A population PK model of
tivozanib was constructed from PK data from Phase I–III studies, to obtain individualized predictions of
steady-state values for average concentration (Cavg). BP was measured at baseline and on Cycle 1 Day 15
(C1D15), C2D1, and C3D1 in the Phase II and III studies, and was binned to the nearest 5 mm Hg. Analysis
focused on BP shifts in 5 mm Hg increments. Serum samples for sVEGFR2 (Phase III only) were collected
at baseline and on C1D15, C2D1, and C2D22–28. Models of drug exposure as predictors of longitudinal
changes in BP and/or sVEGFR2 were constructed by non-linear, mixed-effects modeling.
Results: Across patients, there was a statistically significant median 5 mm Hg increase in diastolic BP on
C1D15, with similar increases noted on C2D1. There was a curvilinear decrease in sVEGFR2 with time. A
maximum effect (Emax) model vs time showed a half-maximal effect occurring in 19.4 (SE=1.7) days, and a
maximal 53% (%CV=4%) decrease in sVEGFR2. There was a statistically significant effect of Cavg on Emax,
with the magnitude of Emax increasing 6% per 10 ng/mL increase in Cavg.
Conclusions: PK/PD analysis of data from tivozanib Phase II–III studies showed that patients had a median
increase in diastolic BP of 5 mm Hg on C1D15 and C2D1. Levels of serum sVEGFR2 were found to decrease
significantly with time, and the effect size increased with tivozanib exposure. Relationships between
exposure, BP, and sVEGFR2 and outcome are being explored.
84
P041
Incidence of local and port site recurrence after laparoscopic surgery for renal cell carcinoma
Garcia-Rojo D., Prera A., Abad Gairin C., Barrio M., Gual J., Martos R., MuГ±oz J., Gonzalez-Sala J.L., Vicente
E., Hannaoui N., Prats J.
Corporacio Parc Tauli, Dept. of Urology, Sabadell, Spain
Material & Methods: Prospective study to determine the incidence of dissemination and port site
metastases in patients undergoing laparoscopic surgery for renal cell carcinoma, with a minimum followup of one year or to death. We analyzed the incidence, type of surgery performed and the method of
extraction of the surgical specimen. From January 2003 to January 2010, 124 laparoscopic procedures for
renal cell carcinoma were performed. Survillance protocol according UCLA integrated staging system was
performed.
Results: Of the 124 patients with renal cell carcinoma, 1 patient (0.8%) developed a peritoneal
dissemination. The histologic type of the renal cell carcinoma was multiple grade 3 papillary cell
carcinoma, stage pT1b. The patient presented a peritoneal carcinomatosis 5 months postoperatively.
The extraction of renal specimen was performed with open laparotomy without using endo-bag (method
used only in the first 8 cases). No port site metastases were observed.
Conclusions: The incidence of recurrence in our serie was closely correlated with the range in previous
reports. The use of endo-bag for extraction of the surgical specimen is imperative in order to tumoral
seeding does not occur.
85
Unmoderated Posters
Introduction & Objectives: Tumor seeding after open and laparoscopic urological surgery is a potential
risk. The rate of tumor seeding varied with the type of tumor. The incidence of local and port site
recurrence after laparoscopic surgery for renal cell carcinoma is extremely low. The few published cases
have been observed when extraction of surgical specimen was performed without endo-bag or if the kidney
was retrieved by mechanical morcellation in plastic bag.
P042
Hand-assisted laparoscopic partial nephrectomies with early removal of renal artery clamps:
A technique description after fifteen cases
Azawi N.H., Christensen T.
Roskilde Hospital, Dept. of Urology, Roskilde, Denmark
Unmoderated Posters
Introduction & Objectives: The incidence of the diagnosis of renal cell carcinoma has increased during
the past two decades. Kidney damage occurring beyond 30 minutes of warm ischemia is significant and
mostly irreversible, even in completely normal renal systems. The aim of study is to evaluating the role and
safety of early removal of renal artery clamps and its influence on warm ischemia time and renal function.
Material & Methods: Data from 15 patients who underwent HALPNs were retrospectively collected.A
paired t–test was used to compare the distribution between eGFR before and after the operations. p<0.05
was considered significant. All patients were followed at least six months after the operation. Procedure:
The kidney was dissected using hand assisted laparoscopic technique, gerotic fascia was dissected and
a complete exploration of the kidney was achieved. A vascular bulldog clamp was removed from the renal
artery immediately after the tumour resection bed had been closed with a running suture with Hemi-O-Luk
clips at either end.
Results: The mean age was 63.4 years (range 51-74). The mean size of the tumours was 3.3 cm (range
2-7). 7 tumours involved the renal collecting system, one tumour was endophytic, and 3 tumours were at
the posterior aspect of the kidney. The PADUA score was 6 in 4 patients, 7 in 5 patients, 8 in 2 patients,
9 in another 2 patients, 10 in one patient and 12 in another. The mean warm ischemia time (WIT) was
11.2 min (range 8-26) and distributed to 26 minutes for one patient and 15 for a second; for the rest, the
ischemia time was less than thirteen minutes. The mean intra-operative estimated blood loss (EBL) was
149 ml (range 100-200). The mean operative time (OT) was 119 min (range 85-180). The mean hospital stay
(HS) was 3.3 days (range 1-6). Clavien classification concerning postoperative complication was one in 12
patients and 2 in 3 patients due to a high fever that was treated by antibiotics. Histological results revealed
thirteen cases with renal cell carcinoma, one oncocytoma and one angiomyolipoma. One patient had a
microscopically positive surgical margin.There was no significant difference between the eGFR before and
six months after operation, with a mean of 71.6 mL/min/1.73 m2 (range 34-97) and 63.8 mL/min/1.73 m2
(range 42-88) respectively (p=0.27).There was no need for postoperative blood transfusions. There was no
delayed bleeding, urinary leakage or re-operation.
Conclusions: Early removal of renal artery clamps during HALPNs is associated with a considerable
decrease in WIT and a preservation of the kidney function estimated from eGFR. HALPN is a safe and
effective treatment for carefully selected patients with small renal cell tumours, but more studies with
longer observation times are needed to evaluate the renal function outcome after HALPNs.
86
P043
Poor survival after laparoscopic radical nephrectomy
D'elia C.1, Luciani L.G.1, Cai T.1, Giusti G.2, Tiscione D.1, Celia A.3, Fiori C.4, Porpiglia F.4, Parma P.5,
Vattovani V.1, Malossini G.1
Santa Chiara Hospital, Dept. of Urology, Trento, Italy, 2Humanitas Hospital, Dept. of Urology, Milan, Italy,
San Bassiano Hospital, Dept. of Urology, Bassano Del Grappa, Italy, 4Orbassano Hospital, Dept. of Urology, Torino, Italy, 5Carlo Poma Hospital, Dept. of Urology, Mantova, Italy
1
3
Material & Methods: The data of patients undergoing LRN for RCC > 7cm from 2002 to 2010 prospectively enrolled at five urologic centers in Northern Italy were reviewed. Complications were graded following
the Clavien-Dindo classification. Overall survival (OS), cancer-specific survival (CSS), and progression-free
survival (PFS) were estimated using the Kaplan-Meier method. CSS estimates were adjusted for tumor
stage: pT2 versus pT3. Patients were followed for a median time of 42 months (range 6-114).
Results: Overall, 222 patients underwent LRN in the study period. Thirty-four cases presenting with distant
metastasis were not considered: therefore, 188 of 222 patients were eligible for final follow-up analysis.
Grade III or more complications and conversions occurred in 5 (2.6%) and 9 cases (4.8%), respectively. 62
(33%) cases were pT3; median tumor size was 8.5cm (range 7-18). 5-yr overall (OS), cancer-specific (CSS),
and progression-free (PFS) survival were 74%, 78%, and 66%, respectively. 5-yr stage-adjusted CSS was
89% and 40% in pT2 and pT3 cases, respectively (p < 0.0001). The median interval to recurrence was 14
months (range 2-62). 22 of 36 patients with recurrence died of disease after a median follow-up time of 26
months. 6 (3.7%) died of unrelated disease.
Conclusions: LRN for large renal tumors is efficacious, with OS and CSS rates comparable with those of
open series after a medium-term follow-up time. However, patients with locally confined RCCs appear to
have a remarkable survival benefit after LRN, whereas pT3 stage RCCs have a significantly lower survival.
In conclusion, survival differences in locally confined or advanced pathologic stage treated by a
laparoscopic approach were strongly accentuated in our series. However, these results need to be
confirmed on a longer follow-up time and on larger surgical series.
87
Unmoderated Posters
Introduction & Objectives: The role of laparoscopic radical nephrectomy (LRN) for large and locally
advanced primary tumors has not been clearly established. Our objective is to evaluate the oncologic
outcome of LRN for large renal cell carcinoma (RCC).
P044
Radiofrequency in the treatment of renal cell carcinoma: Experience in Parc Tauli Hospital
Gual Frau J., Fadil Hechadi Y., Martos Calvo R., MuГ±oz Rodriguez J., Barrio MuГ±oz M., Abad Gairin C.,
Garcia Rojo D., Gonzalez Sala J.L., Hannaoui Hadi N., Prera Vilaseca A., Vicente Palacio E.
CorporaciГі Sanitaria Parc Tauli, Dept. of Urology, Sabadell, Spain
Unmoderated Posters
Introduction & Objectives: Radiofrequency ablation (RF) is a technique currently used for percutaneous
treatment of renal cell carcinoma, being considered one of the less invasive techniques. The indication of
RF, basing on the European Guidelines of urology are one-kidney patients at risk of loss of renal function,
patients with significant comorbidity and elderly patients with small lesions, asymptomatic patients with
bilateral tumors and patients with genetic predisposition to develop multiple renal tumors.
Material & Methods: From November 2005 to August 2011 were treated 33 suffering from renal tumor
with percutaneous renal radiofrequency with an access guided by Computed Tomography (CT). To study
the comorbidity we used the ASA (American Society of Anesthesiologists) scale. The radiological complete
response is considered by the absence in contrast capturing.
Results: Mean age 78 years (44-88), mean lesion size 2.78 cm (1-5 cm.). 28 patients (84.8%) were undergone previous biopsy, 14 of whom (50%) was consistent with clear cell carcinoma, 7 chromophobe/oncocytic strokes carcinoma (25%), 4 inconclusive biopsy (14.3%) and 3 papillary carcinoma (10.7%). 2 patients
ASA II (being the 2 single kidney), 12 patients ASA III, 19 patients ASA IV. Of the 33 patients, 26 (78.8%)
achieved a complete response relapsed in the first month CT, 5 patients in the second treatment, and the
2 remaining in the third treatment. Therefore, all patients achieved a complete response. Complications:
perirenal haematoma in 5 patients, 2 peritumoral haematoma, 1 liver laceration and 1 intracystic bleeding
(requiring embolization).
Conclusions: The current "gold standard" for treatment of renal lesions remains radical renal surgery
with laparoscopic access. Regarding RF, the high rate of success of this minimally invasive percutaneous
procedure and the low complication rate, does consider this technique as an alternative to the treatment of
kidney tumor lesions, especially in older patients, patients with more surgical risk and with more comorbid
conditions.
88
P045
Laparoscopic partial nephrectomy with radiofrequency ablation
Alekseev B.Y., Kalpinskiy A.S., Nyushko K.M., Polyakov V.A., Vorobyev N., Andrianov A.N.
Moscow Hertzen Oncology Institute, Dept. of Oncourology, Moscow, Russia
Material & Methods: LPN was performed in 122 patients in 2003-2012 in our institution. In 51 (41,8%)
patients standard LPN was performed, and in 71 (58,2%) – LPN with RFA. Each procedure was performed
by a single, experienced laparoscopic surgeon. A mean size of a tumor was either comparable in both
groups according to CT (p>0,05): 31,7В±11.5 mm (10-60 mm) in the group of standard LPN and 28,1В±11,6
mm (11-80 mm) in LPN with RFA group. All operative interventions were transperitoneal. The monopolar
Cool-tipВ® RF system (Tyco Valleylab, USA) was used with one-needle probe (17Gauge, length 20 cm, working
surface 20 mm) and a set of passive electrodes. Probe introduction was made under the ultrasound control on a assume line of a resection with setback 5-7 mm from tumor edge. The time of each RFA point was
about 2 minutes and depend on tissue resistance. Neither warm nor cold renal ischemia was done.
Results: Groups of patients were comparable regarding to mean operating time, median of duration of
hospitalization, rate of complications and follow up time. The significant difference was observed only in
median of blood loss. The median blood loss for group of standard LPN was 300 ml (50-2800) and 100 ml
(50-1100) for LPN with RFA (СЂ<0.001). Mean operating time was 137.8 + 60.8 min (60-360) in the group
of standard LPN and 117.1+30.2 min (75-200) in LPN with RFA (p=0.14). Positive surgical margins were
not observed. The frequency of intra- and postoperative complications in both groups were comparable
- 11.8% and 16.9%. Most complications were met at the stage of technique development. A correlation
between the tumor localization (intraparenchymal or extrarenal) and a frequency of complications was
observed, with complications more frequent in patients with intraparenchymal localization (R=0.25,
p<0.01). The mean of follow up time in group of standard LPN was 49,3 + 40,2 months (1 - 102), and 31,7
+ 16,7 months (1 - 63) in group of LPN with RFA (p>0.05). Local recurrence and disease progression were
not observed during the follow up period. All patients are still alive with preserved renal function.
Conclusions: The new radiofrequency-based LPN technique allows to perform an efficient and rapid LPN
without need in kidney ischemia and to reduce the blood loss. Preservation of tissue structure and a
minimal collateral tissue damage allows to interpret resection margins.
89
Unmoderated Posters
Introduction & Objectives: Main problems of laparoscopic partial nephrectomy (LPN) are difficulties in
assessing of adequate haemostasis and necessity of renal ischemia. We present our experience of new
technique of LPN with radiofrequency ablation (RFA) without ischemia comparing with standard technique
of LPN.
P046
Comparison of laparoscopic and open partial nephrectomies: Single center experience
Alekseev B.Ya., Kalpinskiy A.S., Nyushko K.M., Polyakov V.A., Vorobyev N.V., Andrianov A.N.
Moscow Hertzen Oncology Institute, Dept. of Oncourology, Moscow, Russia
Introduction & Objectives: Open partial nephrectomy (OPN) is an established treatment for small renal
masses. Laparoscopic partial nephrectomy (LPN) is an increasingly performed, minimally invasive
alternative to OPN. The aim of our study was to compare early postoperative outcomes in patients who
had undergone OPN with the initial experience of LPN in patients with a single renal tumor.
Unmoderated Posters
Material & Methods: We analyzed database of 418 patients who had undergone OPN and LPN. We
selected 2 comparable groups of patient with different approaches. LPN was performed in 122 patients
and OPN – in 150 patients. LPN was performed in standard variant with or without ischemia and modified
LPN with RFA.
Results: Patients who had undergone OPN compared to the LPN group were at higher risk of symptomatically tumors with increased tumor size and intraparenchymal tumor localization (p<0.05). A mean size of a
tumor according to morphological examination was higher in OPN group than in the LPN group of patients:
38.5В±22mm (8-180mm) and 25.9В±12.5mm (5-85mm) respectively. Groups of patients were comparable
by ischemia time and rate of complications (p>0.05). The significant differences were observed in median
blood loss and mean operating time. The median blood loss for group of OPN was 700ml (50-4000) and
150ml (50-2800) for LPN (СЂ<0.001). Mean operating time was 175.5+56.9min (60-360) in OPN group
and 124.7+44.8min (60-360) in LPN (СЂ<0.05). Positive surgical margins were not observed. Frequency of
intra- and postoperative complications in OPN and LPN groups were comparable - 13.9% and 15.6%. Most
complications were observed at the beginning of learning curve. Correlation between tumor localization
(intraparenchymal or extrarenal) and a frequency of complications was observed, with complications more
frequent in patients with intraparenchymal localization (R=0.14, p<0.05). Levels of creatinine and urea were
similar in both groups.
Conclusions: Early experience of LPN is promising. LPN offered the advantages of less operative time
and decreased operative blood loss.
90
P047
Cardiotoxicity in metastatic renal cell carcinoma (mRCC) patients (pts) treated with
sunitinib (SU)
Prati, V.1, Ballatore, V.1, Ruatta, F.1, Bonzano, A.2, Galizia, D.1, Aglietta, M.1, Ortega, C.1
Fondazione Del Piemonte Per L’Oncologia - Institute For Cancer Research and Treatment, Dept. of Medical
Oncology, Candiolo (turin), Italy, 2Fondazione Del Piemonte Per L’Oncologia - Institute For Cancer Research
and Treatment, Dept. of Cardiology, Candiolo (turin), Italy
1
Material & Methods: Between April 2007 and December 2011, a total of 33 consecutive pts, median
age 65 yrs (41-80), were treated with SU. The median treatment duration was 8,3 months (0,4-22,1). All
patients were analyzed for CAD risk factors (hypertension, hypercholesterolemia, diabetes, smoking),
rhythm disturbances and heart failure. ECG, echocardiography and cardiology consultation were
performed at baseline and every three months until progression disease or SU permanent discontinuation.
We prospectively recorded the following pts features: left ventricular ejection fraction (LVEF),
cardiovascular history, blood pressure, and antihypertensive therapy. For 14/33 pts we also recorded at
the same intervals patterns of mitral valve inflow. We defined cardio toxicity as a reduction of LVEF ≥10%.
Results: At baseline LVEF media was 66% (85%-55%), with a statistically significant (p=0.003) reduction
to 61% on SU treatment (77%-45%). 16 out of 33 pts (48,5%) had a reduction of LVEF ≥ 10% during
the treatment. 15 of these 16 pts were asymptomatic and only one showed symptoms of CHF (global
myocardial hypokinesia) and temporarily discontinued SU. At baseline 23 pts (69,7%) had hypertensive
disease (HD) but neither this CAD risk factor nor hypercholesterolemia, diabetes and smoking resulted
predictive of cardiotoxicity. On SU therapy 5 out of 23 pts worsened the preexisting HD, which was
controlled with adequate medical treatment and did not determine SU discontinuation. Furthermore 7 pts
(21,2%) developed HD. 14/33 pts were also evaluated for diastolic function. At baseline we recorded 7
pts (50%) with normal mitral valve inflow pattern and 7 (50%) with impaired left ventricular (LV) relaxation.
On SU therapy pts with this last pattern did not experience changes, but 6/7 pts (85,7%) with normal left
ventricular (LV) relaxation at baseline developed a LV relaxation worsening.
Conclusions: We found a percentage of cardiotoxicity higher than which was reported at ASCO meeting.
Probably this is due to the lower cut off of LVEF reduction we used and to the metastatic setting we
considered. Analysis of diastolic function may play a useful role in early detection of myocardial damage.
On the basis our results, despite the new encouraging data of cardiosafety, we continue to recommend a
careful cardiac evaluation in all patients before starting and during SU treatment.
91
Unmoderated Posters
Introduction & Objectives: Cardiovascular events (CVE) may occur in up to 10% of pts with mRCC
treated with SU. Recently at ASCO meeting results of cardiosafety in adjuvant tyrosine kinase inhibitors
(TKIs) treatment in RCC have been reported. Cardiotoxicity (LVEF–Left Ventricular Ejection Fractionreduction >16%) was < 5%. We have prospectively analyzed pts with mRCC naïve for therapies with TKIs
receiving SU.
P048
Clinical hypothyroidism as a prognostic factor for advanced renal cell carcinoma treated with
sunitinib: A retrospective analysis
Sym S.J.1, Park J.1, Hong J.1, Ahn H.K.1, Cho E.K.1, Jung H.2, Yoon S.J.2, Lee J.H.1, Shin D.B.1
1
Gachon University Gil Hospital, Dept. of Internal Medicine, Incheon, South Korea, 2Gachon University Gil
Hospital, Dept. of Urology, Incheon, South Korea
Unmoderated Posters
Introduction & Objectives: Hypothyroidism has been observed to occur early as well as late during
treatment with sunitinib, a multiple tyrosine kinase inhibitor. We investigated whether the occurrence of
hypothyroidism during treatment with sunitinib affects the outcome of patients (pts) with metastatic renal
cell carcinoma (mRCC).
Material & Methods: A total of 42 consecutive pts with mRCC treated with sunitinib in a single center
between January 2007 and May 2012 were included in this study. Thyroid function was assessed at
baseline and each 6 or 12 weeks during treatment. Subclinical hypothyroidism was characterized by
serum thyroid-stimulating hormone (TSH) above the upper limit of normal and free thyroxine (free T4) within
normal limits. Clinical hypothyroidism was defined as low free T4 with elevated TSH.
Results: Median age was 59.6 years (range 36-78; 34 male and 8 female). One pts presented an
abnormal baseline thyroid function and 3 pts were not evaluable for thyroid function. Out of 38 pts who
were evaluable for thyroid function test results at baseline and during treatment, 25 pts (65.7%) developed
sub- (36.8%) or clinical hypothyroidism (28.9%) and required hormone replacement during sunitnib treatment. Thirteen pts (34.2%) did not develop any biochemical thyroid abnormality. Median time to developing
clinical hypothyroidism was 6.1 months. There was a statistically significant correlation between the
occurrence of clinical hypothyroidism during treatment and the rate of objective response (P<0.001),
median progression free survival (P=0.015) and overall survival (P=0.022).
Conclusions: The development of clinical hypothyroidism during treatment might be useful as a predictor
of treatment outcome for patients undergoing treatment with sunitinib.
92
P049
Effect of prior metformin Intake on first diagnosis of prostate cancer in diabetic men
Gupta S.1, Singh A.2, Jagar P.3, Giese G.2, Patil S.2, Lad T.E.1
1
John H Stroger Jr Hospital of Cook County, Dept. of Hematology-Oncology, Chicago, Il, United States
of America, 2John H Stroger Jr Hospital of Cook County, Dept. of Medicine, Chicago, Il, United States of
America, 3Satyabhama Hospital, Dept. of General Medicine, Delhi, India
Material & Methods: All patients with a diagnosis of prostate cancer between 2005 and 2008 were
identified from the tumor registry of our hospital. From this group, all patients with diagnosis of diabetes
before prostate cancer were identified and included in the study. Patients with diagnosis of diabetes with
or after prostate cancer diagnosis were excluded. All charts were retrospectively reviewed to confirm the
first diagnosis of prostate cancer, documentation of diabetes treatment and a full biopsy report. Patients
with no pathology report, non-diabetics and incomplete data were excluded. A note was made of the type
of diabetes treatment, duration of metformin intake, metastatic stage or lymph node involvement, PSA at
diagnosis, age, race and Gleason’s score. Patients with less than 6 month intake of metformin were also
excluded. The difference in means and percentages were calculated using the 2-sample t-test.
Results: A total of 660 patients were screened of which 117 diabetics were identified and 101 met the
inclusion criteria. Fifty-seven patients were taking metformin for an average of 34 months before cancer
diagnosis and 44 patients were diabetics not on metformin. The average age of patients on metformin
was 63.9 years compared to 66.6 for non-metformin group (p = 0.03). The mean Gleason score between
the groups was 6.48 versus 6.73 for non-diabetics (P=not significant (NS)). Average PSA at diagnosis was
34.2 for metformin compared to 85.4 for non-metformin groups (p=NS). Patients on metformin were less
likely to present with regional lymph node and distant metastatic disease compared to non-metformin
group, 1.7% versus 11.4% (p=0.03). When comparison was made between insulin taking and non-insulin
taking groups there was no statistical significance between average age and Gleason score, however there
was a trend towards a higher rate of locally advanced or metastatic disease at diagnosis for insulin group
compared to non-insulin group, 13.3% vs. 2.9% (p=0.06).
Conclusions: Prior intake of metformin in diabetic men may lead to a more localized prostate cancer
diagnosis, suggesting a possible role for primary prevention in these patients or subgroups that may be at
a higher risk for development of prostate cancer. Further larger prospective studies are needed to clarify
the finding.
93
Unmoderated Posters
Introduction & Objectives: There is a growing interest in the Oncology community regarding the
chemo-preventive effects of metformin, a very old medication used for treating Diabetes Mellitus. Although
diabetes is associated with a lower prostate cancer risk, Jayachandran et al (Cancer Epidemiol Biomarkers
Prev. 2010 Jan;19(1):9-17.) reported diabetes to be associated with higher grade tumors at recurrence. We
undertook this study to see if prior intake of metformin in patients with newly diagnosed prostate cancer
affected the diagnostic parameters in any way.
P050
Incidental prostate adenocarcinoma – 4 years experience
Nunes A., Pereira S., Martinho D., LeitГЈo T., Fernandes J., Sandul A., Garcia R., Silva R., Gaspar S., Lopes T.
Hospital Santa Maria - Centro Hospitalar Lisboa Norte, Dept. of Urology, Lisbon, Portugal
Unmoderated Posters
Introduction & Objectives: Before the generalized use of PSA, localized prostate cancers [PCa] were
only identified through histological examination of transurethral resection of the prostate [TURP] or open
adenomectomy [OA] specimens, with rates varying between 10 to 31%. Nowadays incidental PCa rates
have decreased to 5-8%. Recent studies showed that incidental PCa isn’t always indolent, presenting a
disease specific mortality rate of 26,6% at 10-years. The purpose of our retrospective study is to evaluate
incidental PCa rate at our institution during a 4-year period of time.
Material & Methods: The files of all patients submitted to TURP and OA at our center over a 48-month
period were analysed (from March 2008 to February 2012). Patients with incidental PCa were analyzed for
age, pre-operative PSA, PSA-density, T-stage, Gleason Score [GS], therapeutic approach and PSA outcome.
Results: From a total of 965 procedures (673 TURP and 292 OA), in 37 (3,83%) an incidental PCa was
found. In this group of patients the mean patient age was 71,9 (В±8,5) years, average pre-operative PSA was
5,0 (В±4,32)ng/ml; 48,6% of the patients (n=18) had T1a stage disease and 51,4% had T1b (n=19). Mean GS
was 5,86 (В±1,05) and PSA density 0,079 (В±0,06). 26 patients were monitored, with average patient followup of 20 (В±13) months; 50% (n=13) were managed with expectant therapy [ET], 15,4% (n=4) with external
beam radiation [EBR], 7,7% (n=2) with radical prostatectomy [RP] and 26,9% (n=7) with hormonal therapy
[HT]. Mean PSA at follow-up was 2,59 (В±2,18)ng/ml. No deaths were reported. One patient managed with
ET had PSA progression and started HT, another had PSA progression under HT and one had biochemical
recurrence after RP.
Conclusions: Despite the systematic use of PSA analysis, incidental PCa is unavoidable, indicating that
this screening method isn’t always accurate. Recent studies demonstrated high long term disease specific
mortality rates which mandate careful follow-up.
94
P051
Prospective randomized controlled trial of the role of PSA and PCA3 testing in a sequential
manner in an opportunistic screening programme for prostate cancer
Rubio-Briones J.1, Casanova J.1, DomГ­nguez-Escrig J.1, Dumont R.1, FernГЎndez-Serra A.2, Casanova-Salas I.2,
Collado A.1, GГіmez-Ferrer A.1, RamГ­rez-Backhaus M.1, Solsona E.1, LГіpez-Guerrero J.A.2
1
Instituto Valenciano De OncologГ­a, Dept. of Urology, Valencia, Spain, 2Instituto Valenciano De OncologГ­a,
Dept. of Molecular Biology, Valencia, Spain
Material & Methods: Valencian government health department and our institutional ethics committee
approved the trial. This prospective study included 1847 men aged between 40 and 75 years with >
10 years of life expectancy who were initially screened with PSA/digital rectal examination (DRE) by an
urologist. Men with PSA <3ng/ml and a normal DRE were followed up depending on PSA values. PCA3 was
performed in men with either an abnormal DRE or if PSA >3ng/ml. All men with PCA3 ≥35 (PCA3 positive)
were biopsied. Men with PCA3 < 35 (PCA3 negative) were randomized 1:1 in a blinded manner wither to
biopsy or observation. Follow up of men with negative prostate biopsy occurs depended on the presence
of risk factors. Re-biopsy criteria are PSA increase >0.5ng/ml at 4-6 months or PSAv >0.75ng/ml/year.
We perform 10-12 cores at the initial biopsy and 14-16 at the second biopsy.
Results: PCA3 testing was performed in 185 (10.01%) men. Fifty-two PCA3 positive men were biopsied
and prostate cancer (PCa) was identified in 17 (16 in first biopsy and 1 in 6 re-biopsies). In the randomized
arm with 133 PCA3 negative men, 83 were observed and 50 were biopsied. There were 6 PCa in first biopsy and 3 more in 15 biopsies during follow up. At a follow up of 18 months, detection rates of PCa in the
PCA3 positive and PCA3 negative groups were 32.6% and 6.7% respectively. From the 9 PCA3 false
negative patients, 3 out of 133 (2.2%) had Gleason 4. PPV of the biopsy in the PCA3 positive group was
30.7%. If PCA3 was used as a second line biomarker to induce biopsy, potentially 71.9% and 60.5%
biopsies would have been saved at the initial and at 18 months follow up, respectively.
Conclusions: Promising preliminary results were shown at 18 months follow up. It will be interesting to
study the characteristics of PCa identified in men who were PCA3 negative initially and whether this will
be an acceptable balance considering the number of biopsies that will be saved. This study is financed by
grants FIS PI10/01206 and FI11/00505 from the Instituto de Salud Carlos III; ACOMP12/029, Generalitat
Valenciana; and Astra Zeneca-Spain.
95
Unmoderated Posters
Introduction & Objectives: Results from the ERSPC with 11 years follow up have shown reduced NNS
and NNT and improved cancer specific survival compared to the control arm but at the expense of too
many negative biopsies. To this effect, we studied the role of PCA3 at a cut-off 35 which has not been
validated in a screening scenario. We present our preliminary results testing PCA3 as a second line biomarker with the main objective of saving biopsies, while reproducing the potential benefits of a screening
program.
P052
Computer-aided ultrasonography: Accurate tool for selecting men for prostate biopsy
De Coninck V.1, Braeckman J.1, Autier P.2, Michielsen D.1
UZ Brussel, Dept. of Urology, Brussels, Belgium, 2International Agency For Research On Cancer,
Dept. of Epidemiology, Lyon, France
1
Unmoderated Posters
Introduction & Objectives: To evaluate the value of computer-aided ultrasonography in selecting patients
for biopsies to detect prostate cancer.
Material & Methods: Over a 6 month period, 94 men were examined with computer-aided ultrasonography. This imaging technique was developed to detect or exclude, to localize and to measure prostate
cancer. The selection criteria were DRE suspicious for prostate cancer, PSA > 4.0 ng/mL, or PSA velocity
> 0.75 ng/mL/year. Men previously diagnosed with prostate cancer were excluded from this study. During
the acquisition phase ultrasonic raw data from a three-dimensional transrectal ultrasound were recorded
and transferred to the computer. The software enables then mathematical processing by characterization
algorithms of patterns specific of nonmalignant and malignant tissues. Possible malignant regions were
indicated in red in the sagittal, axial and coronal plane of the prostate. A special volumetric tool enabled
fine measurement of total prostate volume and suspicious lesion volume. If the lesions seemed clinically
relevant, prostate biopsies were performed. Multivariate logistic regression was used to estimate the
probability of a positive biopsy. The Wilcoxon Rank Sum test, the Kruskal-Wallis test and the Wald test were
used to determine the statistical significance for the comparison of data between groups of patients.
Results: After univariate analysis, volumes of suspicious lesions measured by computer-aided ultrasonography were significantly higher in men diagnosed with prostate cancer. The computer-aided ultrasound
results correlated positively with suspicious DRE. At logistic regression analysis, adjusted for age, DRE,
serum PSA level, prostate volume and suspicious lesion volume, every cancer volume increase of one milliliter estimated by computer-aided ultrasonography was associated with a nearly three-fold increase in the
probability to have a positive biopsy (odds ratio:2.9; 95% confidence interval 1.2-7.0; p-value 0.02).
В median age (years)
PSA (ng/mL)
PSA density (ng/mLВІ)
DRE
prostate volume (mL)
suspicious lesion volume (mL)
В cancer found
(n=17)
no cancer found (n=77)
p-value
0.575
median
63
63
min-25%-75%-max
48-60-68-84
46-57-69-78
median
9.4
5.7
min-25%-75%-max
5.11-8.55-15.3-76.34
0.76-3.7-9.17-27
median
0.26
0.13
min-25%-75%-max
0.15-0.20-0.42-1.31
0.03-0.08-0.18-0.85
suspicious
7
10
normal
10
67
median
40
42
min-25%-75%-max
16-32-48-84
18-33-53-110
median
0.85
0.09
min-25%-75%-max
0-0.55-1.2-5.14
0-0-0.50-4.18
Table 1: Comparison of clinical characteristics of the 94 patients whether or not diagnosed with prostate cancer.
96
0.0007
0.0000
0.0063
0.3021
0.0001
В В suspicious lesion volume (mL)
median
min-25%-75%-max
DRE suspicious (n=17)
DRE normal
(n=77)
p-value
0.93
0.08
0.0002
0.05-0.30-1.30-5.14
0-0-0.56-3.42
Table 2: Comparison of suspicious lesion volume of the 94 patients according to the DRE outcome.
odds ratio
95% C.I.
p-value
age
1.0121
0.924
-
1.109
0.796
DRE
1.7776
0.368
-
8.588
0.4741
suspicious lesion volume
2.8608
1.165
-
7.028
0.0219
PSA
1.1529
1.033
-
1.287
0.0113
prostate volume
0.9183
0.863
-
0.977
0.0072
Unmoderated Posters
Term
Table 3: Logistic regression model for prediction of positive biopsy in 94 patients.
Conclusions: We conclude that computer-aided ultrasonography has great ability to select patients that
should undergo prostate biopsy.
97
P053
Transurethral resection of the prostate (TURP) and incidental prostate cancer in a
contemporary single institution series
Rijo E., Pino L., Lorente J.A., Bielsa O., Ubre A., Fumado L., Rodriguez A., Arango O.
Hospital Del Mar, Dept. of Urology, Barcelona, Spain
Unmoderated Posters
Introduction & Objectives: Many patients undergo PSA screening, digital rectal examination (DRE) and
prostate biopsy prior to surgical management of benign prostatic hyperplasia (BPH). Incidental prostate
cancer is found in about 1-12% of patients undergoing transurethral or open surgery for treatment of BPH.
Objective: To evaluate the incidence of incidental prostate cancer detected at transurethral resection of
the prostate (TURP).
Material & Methods: A retrospective review was performed on all TURP specimens performed from
June 2002 to June 2012 at a single institution. A total of 700 men (age 50-88). All patients were evaluated
preoperatively with digital rectal examination (DRE) and prostate specific antigen (PSA) screening. Those
with a diagnosis of prostate cancer prior to transurethral resection were excluded from analysis (n=11). We
recorded the total number of prostate cancer in TURP specimen.
Results: Prostate cancer was incidentally detected in 12 patients (1.7%) on final pathology. 677 (98.3%)
patients demonstrated benign pathology with no evidence of carcinoma (BPH or inflamation). The mean
patient age was 70 years (range 50-88). All were found to have low grade and low volume disease.
Specifically, all nine patients had Gleason 3+3=6 prostate cancer. The volume of cancer in the specimens
ranged from 1%-5%.
Conclusions: With the current widespread use of PSA testing and the vast majority of BPH patients are
screened for prostate cancer with DRE and many undergo prostate biopsy prior to surgical management
of benign disease. The incidental prostate cancer in TURP specimen are relatively uncommon. Our series
of incidental TURP-detected prostate cancer showed and incidence of 1.29% (incidence in keeping with
published data). Further studies are needed to determine the value of extensive pathologic review of TURP
specimens and costs.
98
P054
Magnetic resonance spectroscopy for early diagnosis of localized prostate cancer
Glybochko P.V.1, Voskanyan G.A.2, Vinarov A.Z.1, Korobkin A.S.3, Shariya M.A.3
First Moscow State Medical University, Uronephrology and Reproductive Health Research Institute,
Moscow, Russia, 2First Moscow State Medical University, Dept. of Urology, Moscow, Russia, 3Cardiology
Research Center, Dept. of Radiology, Moscow, Russia
1
Material & Methods: The study included 36 men (aged 49-81 years, mean age 69В±6.45) with suspected PCa for elevated total PSA level (4.52-53.4 ng/ml, median 7.82В±9.01 ng/ml) and no signs of disease
on digital rectal examination (DRE) transrectal ultrasound (TRUS) of prostate, and negative bone scans
for PSA>20 ng/ml. MRS was performed with "Philips Achieva 3T TX" MR scanner implying use of 3 Tesla
magnetic flux density external (not endorectal) magnetic coil. The spectroscopic scanning was carried out
after the native stage of MRI and was followed by diffusion MRI (dMRI) and contrast-enhanced imaging if any
pathologic signs were see in native T2-weighted scans. The scanning of PCa/normal tissue spectrum was
performed in 7x7x7 mm voxels, followed by water/fat noise suppression. Using the only borderline parameter (Cho+Cr)/Cit ≥ 0,48±0,11. All patients subsequently underwent transrectal needle prostate biopsy
for histological assessment of diagnosis. We estimated the correlation between spectroscopic sings of
PCa, histological verification of prostatic intraepithelial neoplasia (PIN) and PCa as well as the concordance
of tumor localization between MRS data and positive biopsy specimens.
Results: The symptoms of PCa on native T2 scans and spectrocopy were found in 13 (36%) and 23 (63%)
of 36 enrolled patients. The tumor was histologically verifiyed 20 of 36 patients (56%). The concurrence of
MRS and morphologic evaluation was observed in 17 (85%) of 20 cases. False positive and false negative
results accounted for 6 (23%) of 23 MRS-positive patients and 3 (15%) of 20 histologically proven cancer
respectively. High grade PIN was detected in all false positive cases. The precise localization was observed
in 14 (82%) of 17 MRS-positive histologically proved tumours, while other three showed a high-grade PIN
in pathlogic spectrum voxels. The evaluated spectroscopic ratio significantly (p<.01) differred between
patient cohorts with histologically proven PCa and without any tumor lesion while a smaller difference was
observed between patients with histologically verified high-grade PIN and without any tumor lesion.
Conclusions: Our results show the sensitivity of MRS as a primary diagnostic technique for LocPCa to be
85% with specificity accounting for 63%. We didn't find MRS capability of reliable distinguishing between
high grade PIN and PCa. The sensivity of MRS was higher than that of routine MRI, including contrastenchanced cases, which resulted in diagnosing 5 additional tumors which were histologically proven
consequently. The visualization ability of magnetic resonance methods allowed for target biopsy. The MRS
specificity was lower compared to routine MRI which may have been due to masking effect of high-grade
PIN and usage of a single spectroscopic parameter. Further investigation is required to assess the role of
MRS in primary diagnosis of LocPCa, optimize its protocol and increase the reliability of technique results
interpretation.
99
Unmoderated Posters
Introduction & Objectives: The objective of our study was to determine the potential role of magnetic
resonance spectroscopy (MRS) as a primary diagnostic tool for localized prostate cancer (LocPCa).
P055
Prostate cancer: A feasibility study for performing MRI before transrectal ultrasound-guided
biopsy
Jalil R.1, Patel N.2, O'neil J.2, Green J.S.A.2
Imperial College London, Dept. of Surgery and Cancer, London, United Kingdom, 2Whipps Cross University
Hospital, Dept. of Urology, London, United Kingdom
1
Unmoderated Posters
Introduction & Objectives: TRUS-guided prostate biopsy remains the state of art in diagnosing prostate
cancer. MRI is a useful tool for its diagnosis and staging. However, if MRI is performed after the TRUS
biopsies, due to haemorrhage and swelling, it may be difficult to stage lesions accordingly so a 4-6 weeks
delay is advised prior to perform MRIs. We discuss a novel idea of performing staging MRI before the TRUS
prostate biopsy using a risk assessment tool of age and PSA.
Material & Methods: A retrospective study enrolled 503 patients who were referred to our hospital with
a suspicion to have prostate cancer. After analysing data from these patients, a tool was developed using
age group and PSA. Ages 60-80 were targeted due to the feasibility of all treatment options. Patients were
grouped into 60-64, 65-69, 70-74 and 75-79. Each group was allocated a PSA range in an attempt to yield
most possible cancer patients who had MRI.
Results: By applying this tool, we identified a subgroup of patients aged 60-79 (n=124) with MRI rates of
48.4% and a cancer rate of 57.3%. These represented 43.3 % of all cancers in this age group 60-79.
Conclusions: Applying this risk assessment tool will identify patients, within an age group that is
amenable for all treatment options of prostate cancer, who can benefit from early MRI and hence
commencement of their definitive treatment without needing to wait 4-6 weeks for MRI after the TRUS
biopsy. Subsequently the cancer target wait will be achieved.
100
P056
Preoperative prognostic factors fail to predict one lobe involvement in patients with clinically
insignificant prostate cancer
Alekseev B.Y., Vorobyev N., Nyushko K.M., Krasheninnikov A.A., Andrianov A.N.
Moscow Hertzen Oncology Institute, Dept. of Oncourology, Moscow, Russia
Material & Methods: 94 patients with insignificant PC were included in analysis. Mean age of patients
was 62.3±6.4 (47-74) years. PSA level ranged from 1.1 to 10 ng/ml (mean – 6.8±2.2). Median percent of
positive biopsy cores was 18.9В±10.1% (7.7-33.3%). Clinical stage T1b was diagnosed in 6 (5.3%) patients,
T1c – in 59 (52.7%) patients, T2a –in 47(42.0%) patients.
Results: The pathological stage pT0N0 was determined in 8(7.1%). After routine morphological examination upgrade of Gleason score (GS) was observed in 10 (8.9%) patients, upgrade of stage from localized to
extracapsular and metastatic (pN+) disease was observed in 12 (10.0%) and 3 (2.7%) patients respectively.
Bilateral tumor extension was revealed in 63 (56.3%) patients. We observed no significant correlation
between preoperative prognostic factors (clinical stage (p=0.9), number of biopsy cores (p=0.8), PSA level
(p=0.5), body mass index (p=0.3), prostate volume (p=0.2), biopsy GS (p=0.2)) and probability of
pathological upgrade of PCa.
Conclusions: The clinical criteria of low volume and low grade PCa are useful for selection patients for
ablative therapy because the rate of stage and grade upgrade after RPE was in our study only 23.3%. On
the contrary these parameters are not suitable for prediction of only one lobe involvement (upgrade to
bilateral extent was 69.6%) and can’t to be used in planning of unilateral ablative therapy.
101
Unmoderated Posters
Introduction & Objectives: The aim of the study was to assess pathological outcomes after radical
prostatectomy (RPE) in patients with unilateral low volume and low grade prostate cancer (PC) and evaluate
prognostic significance of preoperative clinical parameters regarding postoperative tumor stage and
grade.
P057
Detection of prostate carcinoma on repeat biopsy by the presence of proliferative inflammatory
atrophy on initial biopsy
Stimac G.1, Dimanovski J.1, Trnski D.1, Skerk V.2, Sonicki Z.3, Tomas D.4, Kruslin B.4, Kraus O.1
Sestre Milosrdnice University Hospital, University Department of Urology, Zagreb, Croatia, 2University
Hospital For Infectious Diseases Dr. Fran Mihaljević, Department For Urogenital Infections and STDs,
Zagreb, Croatia, 3School of Public Health, Faculty of Medicine, University of Zagreb, Department of Medical
Statistics, Epidemiology and Medical Informatics, Zagreb, Croatia, 4Sestre Milosrdnice University Hospital,
University Department of Pathology, Zagreb, Croatia
1
Unmoderated Posters
Introduction & Objectives: The aim of the study was to assess the risk of detecting prostate carcinoma
on repeat biopsy based on the pre-biopsy PSA levels, presence and morphological characteristics of
inflammation and proliferative inflammatory atrophy (PIA) lesions on initial biopsy.
Material & Methods: Study included 208 patients with PSA level≤10 ng/mL, submitted to repeat biopsy
during the 2003-2011 period. The presence and number of PIA lesions were determined on initial biopsy,
while a modified system of inflammation type and aggressiveness grading, developed by Irani et al, was
used for pathomorphological analysis. Factor analysis was used to assign specific inflammatory factor
score to each subject. Patients were divided into two groups according to the type (more chronic, more
acute) and aggressiveness (less and more aggressive) of inflammation, and also according to the presence
of PIA. The presence of carcinoma was determined on repeat biopsy.
Results: Only 5.80% of subjects were free from inflammation. PIA was detected in 39.40% of patients. The
majority of PIA were grouped in cores with chronic (88.20%) and non-aggressive (72.67%) inflammation.
Spearman's analysis yielded a significant negative correlation of the number of PIA with the inflammation
type (p = 0.002) and aggressiveness (p < 0.001) factor scores. Acute and more aggressive inflammation
caused a significant decrease in FPSA and F/TPSA values (p < 0.001 both). Kaplan-Meier analysis indicated
the risk of carcinoma detection on repeat biopsy to be greater in subjects with more chronic (p < 0.001)
and less aggressive (p = 0.023) inflammation. The rate of PIA on initial biopsy was significantly higher in
the group of subjects with carcinoma on repeat biopsy (p < 0.001). The subjects with carcinoma had a
significantly greater number of PIA lesions per initial biopsy set (p < 0.001). Kaplan-Meier analysis yielded a
higher risk of carcinoma detection in the group of subjects with PIA on initial biopsy (p < 0.001). ROC
analysis yielded the optimal borderline PIA number on initial biopsy for the diagnosis of carcinoma on
repeat biopsy of 1.01 (sensitivity 0.368, specificity 0.922); thus, subjects with two or more PIA lesions
were at a higher risk of carcinoma detection on repeat biopsy (p < 0.001). Like carcinoma, the majority
of PIA lesions (85.97%) were located in the peripheral zone of the prostate, while only 14.03% were found
in the transition zone. On initial biopsy, a significantly greater proportion of PIA lesions were grouped in
biopsy cores with carcinoma subsequently detected on repeat biopsy (p < 0,05). The number of PIA lesions
and age showed greatest independent predictive power as risk factors for the diagnosis of carcinoma on
repeat biopsy (OR = 2.537; p < 0.001 and OR=1.060; p = 0.039, respectively), whereas F/TPSA and
inflammation factor score conferred a protective effect from prostate carcinoma (OR = 0.762; p < 0.001
and OR = 0.056; p < 0.001, respectively).
Conclusions: Study results indicate that the presence of PIA in biopsy is associated with a higher risk of
subsequent carcinoma detection. Thus, PIA should be characterized as a facultative precancerous lesion.
Acute inflammation has a protective role through its effect on FPSA levels. Following negative biopsy
findings in patients with borderline PSA, timely recognition of histologic inflammation and related PIA may
point to the need of closer follow up and earlier repeat biopsy.
102
P058
In the era of emerging Fluoroquinolone resistant Enterobacteria, shall we modify our antibiotic
prophylaxis for transrectal ultrasound-guided prostate biopsies?
Benchikh El Fegoun A.1, Jolivet S.2, Dumortier C.2, Armand Lefevre L.2, Bouaita M.2, Ravery V.1, Lucet J.C.2
Hopital Bichat Claude Bernard, University Paris VII, APHP, HUPNVS, Dept. of Urology, Paris, France
Hopital Bichat Claude Bernard, University Paris VII, APHP, HUPNVS, Dept. of Infectious Disease Control,
Paris, France
1
2
Material & Methods: 2144 patients underwent TRUS-guided prostate biopsy (TRUSpb) at our academic
center from January 2005 to December 2010. Patients received 500 mg of Ciprofloxacin in the
morning before TRUSpb were performed. We retrospectively reviewed the records of all patients who were
re-admitted in the month following the procedure or who were discharged after more than 3 days after
TRUSpb and who had a positive blood and/or urine culture. Patients without symptoms of infection, or with
colonized urine were excluded. The annual incidence of infective complications and FQ resistant infections
was calculated and presented by period 2005-2007 (group A), 2008-2010 (group B). Comparisons were
made between the groups using two-tailed Fisher's exact tests.
Results: 22 patients (1%) presented with infective symptoms after biopsy, including 1 with a severe
infection and 1 with a septic shock. Median age was 64 years old. Median time to infection was 2 days
(0-13 days; IQR 1-4 days). When stratified by period, there was no difference in the incidence of infective
complications and FQ resistance between 2005-2007 (0.8%) and 2008-2010 (1.2%) (p>0.5). 17 bacteria
were identified (78%), including 16 Eb (15 E.coli and 1 M. morganii) and 1 P. aeruginosa. FQ resistance was
present in 44% (7/15) and this was comparable between group A(2/5) and B(5/11).
Conclusions: Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies in the
era of emerging FQ resistant Enterobacteria. There is no need to modify our prophylaxis of TRUS-guided
prostate biopsy for the moment.
103
Unmoderated Posters
Introduction & Objectives: Fluoroquinolones (FQ) have been shown to decrease infective complications
after prostate biopsy. However, FQ resistance has emerged. Between 2005 and 2010, the incidence of FQ
resistant Enterobacteria (Eb) has increased from 14 to 23% in our academic hospital and from 14 to 21%
in France. We quantified contemporary rates of infective complications and the incidence of FQ resistant
infections after prostate biopsy under FQ prophylaxis.
P059
Are still fluorquinolones the gold standard in prostate biopsy prophylaxis?
Moreno AlarcГіn C.1, LГіpez Cubillana P.1, LГіpez GonzГЎlez P.1, Olarte BarragГЎn E.1, PinzГіn Navarrete C.1,
Prieto GonzГЎlez A.1, Escudero Bregante F.1, GutiГ©rrez GutiГ©rrez P.1, Cao Avellaneda E.2, Moreno AvilГ©s J.2,
GuzmГЎn MartГ­nez-Valls P.3, GГіmez GГіmez G.1
1
University Hospital Virgen De La Arrixaca, Dept. of Urology, Murcia, Spain, 2University Hospital Santa
LucГ­a, Dept. of Urology, Cartagena, Spain, 3University Hospital Los Arcos, Dept. of Urology, San Javier,
Spain
Unmoderated Posters
Introduction & Objectives: A critical review of previous papers about antibiotic prophylaxis in transrectal
prostate biopsy and compare them with the results of our institution.
Material & Methods: A MEDLINE search with the terms prostatitis, transrectal biopsy and antibiotic
prophylaxis were performed. From a total of 363 patients undergoing transrectal prostate biopsy of the
prostate during three years we recorded 20 cases of postbiopsy fever (5,5%). Antibiotic prophylaxis with
Ciprofloxacine 500 mgr during 10 days was used. Symptoms, blood and urine tests, hemoculture and
uroculture were analyzed.
Results: The incidence of infectious complications after prostate biopsy remains high despite the use of
antibiotic prophylaxis with ciprofloxacine. Recent studies have found infection rates of 0-6,6% in this group
of patients (table). Eighty percent of them were caused by quinolone-resistant pathogens (E. Coli). But problems like the oligosymptomatic cases or negative cultures could make dificult reporting the consequences or knowing the real morbidity of the biopsy by the institutions. Patients with postbiopsy fever in our
study present positive urine culture in seven cases (35%): E. Coli in six cases and Staphylococcus hominis
in one case. Antibiogram showed resistance to quinolones, cotrimoxazole and ampiciline.
Serie
Year
N
Number of cores
Use of enema
Fever
(%)
RAO
(%)
Rietbergen
1997
1687
6-7
No
4.2
0.4
Sieber
1997
4439
6-8
No
-
-
Enlund
1997
426
1-8
Yes
2.9
0.2
RodrГ­guez
1998
129
6
Yes
1.7
1.6
Deliveliotis
1999
120
6
No
6.6
4.6
Manseck
2000
162
10
-
0.6
0
Djavan
2001
1015
8
-
3.8
2.6
Peyromaure
2002
289
10
Yes
3.7
-
Raaijmakers
2002
5802
6-7
No
3.5
0.4
Mari
2007
432
8-12
-
0.94
-
U.H.V.A.
2012
363
8-12
Yes
5.5
0,1
Conclusions: Unfortunately, we were unable to define a population at low risk from infections caused by
resistant microorganisms. We only have found a higher risk in patients with previous use of quinolones for
other infectious disease or prophylaxis. The increasing incidence of quinolone resistance could lead us to
change the antibiotic prophylaxis in urologic procedures. As well as developing new antibiotics we might
try usual antibiotics that are not recommended in guidelines for prostate biopsy prophylaxis to avoid the
infectious complications. With this aim we have initiated a radomized, prospective and multicentre study
comparing quinolone prophylaxis with fosfomicine, which has been demonstrated to get good
concentrations inside prostate parenchyma.
104
P060
Panel of molecular markers for prostate cancer diagnosis
Apolikhin O.I., Sivkov A.V., Severin S.E., Keshishev N.G.
Federal State Budget Research Institute of Urology, Dept. of Innovations, Moscow, Russia
Introduction & Objectives: The most important changes on molecular level affiliated by prostate cancer
are epigenetic alterations of genetic materials including aberrant DNA methylation. We have investigated a
panel of molecular markers of DNA methylation GSTПЂ1,TMPRSS2, RARОІ2 and RASSF1A in order to create a
test-system for diagnosis and management of prostate cancer.
Results: Analyzed diagnostic characteristics of a molecular markers` panel calculated on batch of DNA
samples excreted from prostate tissue, test-sensitivity was 86.3%, specificity was 76.6%. Sensitivity of
markers calculated on batch of DNA samples excreted from urine was 72.5% and specificity was 44.6%.
Sensitivity of markers calculated on batch of DNA samples excreted from blood was 67.1% and specificity
was 52.2%, from lymphocytes - 66% and 61.7% respectively.
Conclusions: Our data demonstrated the existence of significant differences in specificity between our
diagnostic panel of markers and PSA. Specificity of markers GST ПЂ1, RARОІ2 and RASSF1A exceed
specificity of PSA (61.7% vs 5%, СЂ<0.05). Excretion of DNA samples from prostate tissue, lymphocytes and
blood were the most effective. Combined application of GST ПЂ1, RARОІ2, RASSF1A and PSA markers will
facilitate more accurate diagnosis.
105
Unmoderated Posters
Material & Methods: 157 patients in age 55-70 years (67,6В±7,7) with PSA level 4-10 ng/ml were included
in our study. Blood, urine samples collected after DRE and prostate tissue received by biopsy were used
like biological materials. On the ground of formed DNA samples’ bank we have performed evaluation of
sensitivity, specificity, positive predictive value and negative predictive value of this panel of PCA markers.
P061
Transrectal ultrasound-guided prostate biopsy in patients long-term receiving aspirin in low
doses
Apolikhin O.I., Sivkov A.V., Keshishev N.G., Kovchenko G.V.
Federal State Budget Research Institute of Urology, Dept. of Innovations, Moscow, Russia
Unmoderated Posters
Introduction & Objectives: There is a great number of patients who have indications for transrectal
ultrasound (TRUS)-guided prostate biopsy and are on chronic treatment with low-dose aspirin for different
cardiovascular disease. The aim is to determine safety of prostate biopsy performance in patients
receiving low-dose aspirin (75-100mg) without interruption before and after prostate biopsy procedure.
Material & Methods: A total of 168 men were enrolled in trial. Patients were randomized in two groups.
Group I included 83 patients on chronic low-dose aspirin medication for primary prevention of cardiovascular disease, group II included 85 patients who didn’t receive any anticoagulation/antiplatelet therapy at
least during three month before biopsy. The TRUS-guide 12 cores multifocal prostate biopsy was performed in two groups according to single protocol. All consecutive men were asked to complete questionnaire
over the 7 days following TRUS biopsy. The questionnaire contained information on presence and severity
of hematuria, rectal bleeding, hematospermia, rectal pain and body temperature increase.
Results: The overall haematuria complication rate was 52/83 patients (43%) in group I (49 - Grade I,
3 - Grade II), 46/85 patients (39%) in group II (Grade I) (p=0.02). No significant difference was found for
the incidence of haemospermia and rectal bleeding between the two groups (4/83 (3%) and 6/85 (5%) in
groups I and II respectively). There was no statistical difference between rectal pain. Non persistent acute
fever was recognized in any patient.
Conclusions: Regular intake of low doses aspirin (75-100 mg) is not associated with significantly
increasing risk of bleeding in patients who undergo transrectal prostate biopsy. According to our data
prostate biopsy can be performed without the interruption of chronic aspirin intake, but require inpatient
care.
106
P064
Institutional variation in prostate cancer care
Verhoeven R.H.A.1, Valery V.E.P.P.1, Koldewijn E.L.2
Eindhoven Cancer Registry / Comprehensive Cancer Centre South, Dept. of Research, Eindhoven,
The Netherlands, 2Catharina Hospital, Dept. of Urology, Eindhoven, The Netherlands
1
Introduction & Objectives: To visualize the institutional variation of care for prostate cancer, we
published a factsheet on the diagnosis and treatment of prostate cancer in 10 hospitals in the South of the
Netherlands.
Results: The published factsheet on prostate cancer care contains 25 figures and 8 tables, here 3 of the
figures are presented. Figure 1. Resection margins after prostatectomy as primary treatment for prostate
cancer patients diagnosed in 2010 according to prostatectomy hospital (n=363).Figure 2. Number of
investigated lymph nodes after prostatectomy as primary treatment for stage cT2 prostate cancer patients
diagnosed in 2008-2010 according to prostatectomy hospital (n=443).Figure 3. Expected and observed
percentage of patients that underwent a prostatectomy as primary treatment for stage cT2 prostate
cancer in 2010 according to hospital of diagnosis (n=360).
Conclusions: There is a considerable institutional variation of primary care for prostate cancer in the
South of the Netherlands. The results of this factsheet will be discussed in a meeting with clinicians, which
will probably result in a reduced institutional variation and subsequently improved quality of care.
107
Unmoderated Posters
Material & Methods: Data of patients diagnosed with prostate cancer in the period 2008-2010 were
retrieved from the Eindhoven Cancer Registry (ECR). Variation in diagnosis and primary treatment of
prostate cancer was analyzed and anonymously presented for the 10 hospitals within the region of the
ECR.
P065
Robotic high-Intensity focused ultrasound (rHIFU) for the hormone-resistant prostate cancer
treatment: 5-years outcome
Solovov V.A.1, Shaplygin L.V.2, Vozdvizhenskiy M.O.3, Khametov R.Z.2
1
Samara Regional Oncology Center, Dept. of Interventional Oncology, Samara, Russia, 2Samara Regional
Oncology Center, Dept. of Urology, Samara, Russia, 3Samara Regional Oncology Center, Dept. of Surgery,
Samara, Russia
Unmoderated Posters
Introduction & Objectives: HIFU shows a successful treatment for locally prostate cancer (PC). Here we
explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer.
Material & Methods: 391 patients were treated in our center in 2007-2012 with failure after hormone
ablation. Median time before hormone-resistance was 23 (6-48) months. In the group with locally PC:
number of patients 146, Gleason ≤7, stage T1-2N0M0, age 69 (60-89) years PSA before treatment 40,0
(5,8-92,9) ng/ml, mean prostate volume - 39,3 (28-92) cc; in the group with locally advanced PC: number
of patients 245, Gleason ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60)
ng/ml, mean prostate volume - 41,2 ( 25-198) cc. Mean follow-up 38 months (3-60).
Results: Median PSA level 12 months after HIFU treatment was 0,4 (0-2,24) ng/ml – locally PC, with locally
advanced - 0,5 (0-48,4) ng/ml, 36 months after HIFU treatment was 2,1 (0,1-19,2) ng/ml – locally PC,
with locally advanced - 4,8 (0,2-48,4) ng/ml. Patients with locally PC had 4,5% of progression, with locally
advanced PC – 25%. Kaplan-Meir analyses of the total group indicated that the risk of progression after 1
year follow-up was 10%, the risk of progression was 27% after 5 years of follow-up.Complications:
incontinence I- II - 17,7%, stricture - 18,2%, fistula – 0,2%.
Conclusions: Our experience showed that ultrasound rHIFU safe, effective in treatment for locally and
locally advanced hormone-resistant prostate cancer.
108
P066
Predictors of upgrading/upsizing after 1-year re-biopsy in men participating in a prospective
active surveillance program
Rancati T.1, Nicolai N.2, Alvisi M.F.1, Colecchia M.3, Salvioni R.2, Villa S.4, Bedini N.4, Biasoni D.2, Marenghi C.1,
Avuzzi B.4, Paolini B.3, Stagni S.2, Magnani T.1, Catania S.1, Valdagni R.5
Fondazione IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program, Milan, Italy, 2Fondazione
IRCCS Istituto Nazionale Dei Tumori, Dept. of Urology, Milan, Italy, 3Fondazione IRCCS Istituto Nazionale Dei
Tumori, Dept. of AnatomoPathology, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of
Radiotherapy, Milan, Italy, 5Fondazione IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program and
Dept. of Radiation Oncology 1, Milan, Italy
1
Material & Methods: Age, iPSA, PSA density, number of positive cores, % of positive cores, max and
average core length containing cancer, number of negative cores at diagnosis, total number of cores
at diagnosis, total number of cores at 1yr-rebiopsy, prostate volume, DRE were considered as factors
potentially influencing upgrading (UPG) /upsizing (UPS). GPS was not considered (all pts had GPS=3+3).
Three separate endpoints were considered: (1) UPS OR UPG; (2) UPG and (3) UPS. Multivariable logistic
regression (MVLR) was used to analyze correlations between variables and endpoints at first re-biopsy.
Results: Statistical analysis was performed on 255pts with complete records (1yr min f-up). 40%pts had a
negative 1yr biopsy (0 positive cores), 45pts had UPS/UPG after re-biopsy, switching to radical treatment.
The endpoint “UPS OR UPG” was only related to prostate volume>60cc (OR=0.27, p=0.04). When UPG
(27pts) was considered separately a 3-variable model was determined (p=0.018, AUC=0.71): age>60yrs
(OR=3.4, p=0.12), PSA density (continuous variable, OR=1.04, p=0.16) and prostate volume>60cc
(OR=0.17, p=0.1). Taking UPS (18pts) as the endpoint, MLVR resulted in a 4-variable model (p=0.03,
AUC=0.73) including: DRE (T2a vs T1c, OR=3.03, p=0.16), total number of cores at 1-yr re-biopsy (discrete
variable, OR=1.14, p=0.18), age>60yrs (OR=0.48, p=0.23) and max core length containing cancer>10%
(OR=3.4, p=0.03).
Conclusions: UPS is strongly related to “volume” variables, and, as a consequence, may be strongly
affected by sampling. UPG is more related to PSA density. It is noteworthy as age has an opposite effect
on the two endpoints (protective for UPS and risk factor for UPG) and that max core length containing
cancer is highly predictive of UPS. Such analysis may generate the hypothesis that two different populations
of PCa pts are subjected to drop-off from AS protocols. Biological and clinical implications deserve further
studies. Supported by Fond Monzino.
109
Unmoderated Posters
Introduction & Objectives: Predictors of upgrading/upsizing after 1-year re-biopsy in men participating
in a prospective active surveillance program.
P067
Comparison of available dynamic techniques for elective nodal irradiation for prostate cancer
patients
UrbaЕ„czyk H.A.1, Hawrylewicz L.2, Kulik R.2, Szczepanik K.1, Ciechowicz J.3
MSC Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Dept. of Radiotherapy, Gliwice,
Poland, 2MSC Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Dept. of Radiotherapy
Planning, Gliwice, Poland, 3Medical University In ЕЃГіdЕє, Computer Laboratory, ЕЃГіdЕє, Poland
1
Unmoderated Posters
Introduction & Objectives: The few recent studies showed that regional lymph node metastases of
prostate cancer (PCa) could be successfully treated. It means that role of pelvic nodes (PN) irradiation
could increase in next period. A problem is rectal and bladder toxicities of this treatment. Intensity
modulated dynamic irradiation techniques (DT) may potentially help to reduce treatment related side
effects. The aim of study is to compare three different radiotherapy techniques: conformal (CRT), static
field intensity modulated (SF IMRT) and rapid arc (RA) for elective pelvic lymph nodes irradiation.
Material & Methods: We analyzed CRT, IMRT and RA plans of irradiation PN for ten patients. PTVs
included PN iliac, iliac external upper then acetabulum, iliac internal and obturatory. Prescribed doses were
44 Gy/22 fractions. We compared the doses delivered to PTV rectum and bladder using dose volume
histograms. The U Mann-Whitney, W Shapiro-Wilk and ANOVA rang Kruskal-Wallis tests were used for
statistical analysis.
Results: The median PTV doses were not statistically different in analyzed plans. The minimum doses
for PTV were significantly lower in IMRT and RA plans but the differences were not clinically significant.
Maximum doses were significantly higher for CRT plans. The doses calculated for rectum and bladder were
statistically significantly lower for dynamic techniques in whole range of volumes and doses. SF IMRT is
the most efficient technique in reducing the dose to bladder. The doses observed in half of the rectum and
bladder volumes bladder were also statistically significant different (p=0.002 for rectum and 0.001 for
bladder). The median doses for rectum were 43.6 Gy for CRT plans, 33.5 Gy for IMRT and 37.9 Gy for RA,
median doses calculated for bladder were 44 Gy for CRT, 35.6 Gy for IMRT and 39.6 Gy for RA.
Conclusions: CRT does not allow to reduce the dose to organs at risk. Both DT reduce the doses to
bladder and rectum while maintaining the high homogenous dose to PTV. SF IMRT is more efficient in
reducing the dose to bladder than RA. SF IMRT technique seems to be better than Rapid Arc for PN
irradiation. It is probably because the nodal PTVs are large and their structures are complicated.
110
P068
Active surveillance in prostate cancer: 7 year experience
Marenghi C.1, Nicolai N.2, Rancati T.1, Alvisi M.F.1, Bellardita L.1, Avuzzi B.3, Stagni S.2, Villa S.3, Magnani T.1,
Bedini N.3, Salvioni R.2, Valdagni R.4
Fondazione IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program, Milan, Italy, 2Fondazione IRCCS
Istituto Nazionale Dei Tumori, Dept. of Urology, Milan, Italy, 3Fondazione IRCCS Istituto Nazionale Dei
Tumori, Dept. of Radiotherapy, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale Dei Tumori, Prostate
Cancer Program and Dept. of Radiation Oncology 1, Milan, Italy
1
Material & Methods: In our Institute patients can enter 2 AS protocols: SAINT and PRIAS. The 2 protocols
have some common entry criteria: initial PSA≤10ng/ml, DRE≤T2 and GPS≤3+3. SAINT requires max 20%
positive cores and max 50% core involvement, while PRIAS max 2 positive cores and PSA density<0.2ng/
ml/cc. Follow-up includes in both cases PSA every 3mos, DRE every 6mos, re-biopsy after 1yr of AS. When
PSA doubling time (DT)=3-10yrs a yearly repeated biopsy is scheduled. Whenever during the follow-up the
PSADT<3yrs, clinical stage is >T2, the re-biopsies show more than 2 (or 20%) positive cores or GPS>3+3,
change to active treatment is advised.
Results: 342 pts were enrolled in AS (February 2012): 120 SAINT and 222 PRIAS.215/342 (62.9%) pts are
still in AS (median f-up of 33mos, range 1.5-96.1; median time in AS 22.5 mos, range 1.5-96.1): 6 pts
dropped out due to comorbidities, 7 due to personal choice (anxiety), 20 due to off-protocol reasons and
1 due non-PCa death. 93/342 (27.2%) pts dropped out because of disease progression/reclassification:
17 due to PSADT, 76 to upgrading and/or upsizing at re-biopsy (41/76 at first re-biopsy). The actuarial
treatment free survival (ATFS) is 81%, 69% and 58% at 15, 27 and 40 months, respectively. To date, no
unfavorable outcome has been observed. Biopsy-related ATFS is related to PSA density<0.10ng/ml/cc
(log-rank test p=0.004, ATFS at 27 mos 84% vs 74%) and prostate volume >60cc (log-rank test p=0.001,
ATFS at 27 mos 93% vs 76%). PSA-related ATFS is correlated to iPSA ≥5ng/ml (p=0.05). Cox model also
suggests a possible correlation between iPSA as a continuous variable and PSA-related ATFS, close to the
limit for the statistical significance which is anyway not reached (p=0.07, HR=1.24).
Conclusions: AS is feasible in selected men with early PCa. 1yr re-biopsy is an important check, which can
be used as a diagnostic clarification point. Biopsy-related ATFS is correlated to PSA density and prostate
volume >60cc (protective factor, which may underline the difficulty of an adequate biopsy sampling in
patients with high-volume prostate). iPSA is related to PSA-related ATFS. Work was partly supported by
Fond Monzino.
111
Unmoderated Posters
Introduction & Objectives: We here present results on 7 year experience in active surveillance (AS).
P069
Early clinical assessment after robotic radiosurgery of local recurrence or isolated pelvic
lymph node in prostate cancer patients
Bolzicco G.1, Baiocchi C.1, Satariano N.2, Binotto L.2, Scalchi P.2, Favretto M.S.1, Messina F.1, Mari C.1,
Bacchiddu S.1
1
San Bortolo Hospital, Dept. of Radiation Oncology, Vicenza, Italy, 2San Bortolo Hospital, Dept. of Medical
Physics, Vicenza, Italy
Unmoderated Posters
Introduction & Objectives: To evaluate the safety and efficacy of CyberKnife-Stereotactic Body Radiation
Therapy (CK-SBRT) in local recurrence or isolated pelvic lymph node in prostate cancer patients (Pts).
Material & Methods: We evaluated 21 consecutives CK-SBRT patients (Pts) ages ranged from 61 to 81
years (median 70 years); 15 Pts had local recurrence (7 after surgery, 5 after radiotherapy and 3 after
surgery+radiotherapy), 5 Pts had single lymph node recurrence and 1 Pt had local and lymph node
recurrence. All patients had diagnosis by biochemical relapse with positive PET 18FCholina or RMN, only
in few cases we performed also biopsy. CT and PET/RMN images fusion was performed for the clinical
target volume delineation. The planning treatment volume (PTV) ranged from 4 to 50 cc (median 18.23 cc).
Prescription dose (at isodose 80%) ranged from 24 to 30 Gy in 3-5 fractions for local recurrences and 24
to 33 Gy in 3 fractions for lymph nodes.
Results: One patient developed severe urinary acute toxicity (grade 3), 6 Pts developed grade 1-2 urinary
acute toxicity; no patients experienced grade 3 acute gastro intestinal toxicity. One patients developed
grade 2 late urinary toxicity and 1 Pt grade 1 late gastro intestinal toxicity. After a median follow up of 15
months (range 3-96 months) we registered 1 disease progression, 3 local relapse (1 infield progression, 1
missing recurrence and 1 new local relapse), 2 lymph node relapse, 1 bone metastasis and 1 lymph node
plus bone metastasis. The patients with clinical progression are alive in androgen deprivation therapy (ADT)
or chemotherapy.
Conclusions: CyberKnife-Stereotactic Body Radiation Therapy is a feasible approach for local recurrence
or isolated pelvic lymph node in prostate cancer with good control and low acute or late toxicity. A longer
follow-up and a larger number of patients are necessary to evaluate its effectiveness.
112
P070
Image-guided robotic radiosurgery treatment as salvage therapy for locally recurrent prostate
cancer
Beltramo G.1, Bergantin A.1, Vavassori A.2, Jereczek-Fossa B.A.2, Martinotti A.S.1, Vite C.1, Bianchi L.C.1,
Zerini D.2, De Cobelli O.3
1
Centro Diagnostico Italiano, Dept. of Cyberknife, Milan, Italy, 2European Institute of Oncology, Dept. of
Radiotherapy, Milan, Italy, 3European Institute of Oncology, Dept.of Urology, Milano, Italy
Material & Methods: Between September 2007 and November 2010, 29 patients diagnosed with biopsy
confirmed locally-recurrent prostate cancer after EBRT and with absence of severe chronic late toxicity
were referred to our Radiotherapy Department for salvage treatment with CK stereotactic radiosurgery.
The median age of the patients at the time of CK was 70 years (range 56-82 years). The median prereirradiation PSA was 3.80 ng.ml (range 2.04 – 22,88). The median time from failure to reirradiation was
46 months (range 9- 120) The EBRT median dose was 78 Gy (range 70-80 Gy). A minimum of three gold
fiducial seeds were implanted in the prostate gland through an ultrasound-guided trans-perineal pre-loaded
needle and one week later a CT scan and a MRI T1-T2 sequence was performed to elaborate treatment
plane after placement of a Foley catheter to show the urethra. Multiplan (version 2.0.5, Accuray, USA) was
employed. The planning treatment volume (PTV) included the GTV expanded by 3 mm in all directions
except posteriorly where 2 mm were added. CK stereotactic radiosurgery protocol provide a prescribed
PTV dose of 30 Gy given in 5 daily fractions of 6 Gy Biochemical failure was defined according to the
Huston-Phoenix Astro 2005 Criteria.
Results: All patients completed planned CyberKnife SRT with a total irradiation time of 5 days (from
Monday to Friday). No protocol violation was registered. After a median follow up of 21 months (range 3-48
months) three patients developed severe urinary acute toxicity (grade 3) and 2 developed grade 3 urinary
late toxicity. No patients experienced grade 3 acute or late gastro intestinal toxicity. In 17 patients we
observed a biochemical failure, 7 patients had local recurrence, 3 patients developed bone metastases, in
7 patients we observed Lymph nodes dissemination.
Conclusions: CyberKnife-based SRT is a feasible approach for locally recurrent prostate cancer, offering
excellent in-field tumor control and low toxicity profile. Further experience and longer follow-up are needed
to evaluate the role of CK in the treatment of local recurrences and to identify patients most likely to
benefit from it.
113
Unmoderated Posters
Introduction & Objectives: Despite improvements in external beam irradiation for prostate cancer, a
significant number of patients develop locally recurrent disease. Salvage local therapy may well induced a
prolonged biochemical remission and, possibly, even cure. We evaluate the feasibility of re-irradiation with
Cyberknife for intra-prostatic recurrence after external beam radiotherapy (EBRT).
P071
Hypofractionated stereotacitc body radiotherapy for localized prostate cancer
Beltramo G.1, Longo G.2, Locatelli C.3, Bergantin A.1, Martinotti A.S.1, Vite C.1
Centro Diagnostico Italiano, Dept. of Cyberknife, Milan, Italy, 2San Carlo Hospital, Dept. of Urology, Milan,
Italy, 3San Carlo Hospital, Dept. of Oncology, Milan, Italy
1
Unmoderated Posters
Introduction & Objectives: Recent technological developments, intensity modulation radiation therapy
and improved target localization, combined with new hypothesis on prostate radiobiology have generated
enthusiasm for hypofractionated regimens. We report our early preliminary experience with Cyberknife
stereotactic radiotherapy in patients with clinically localized prostate cancer.
Material & Methods: Between July 2007 and October 2010, 73 patients with a median age of 74 years
(range 60 – 86), with T1c –T2 b prostate cancer were treated with Cyberknife stereotactic radiosurgery
as primary therapy at our institution. The majority of patients, 55 had Gleason Score 6, 12 patients
had Gleason Score 7, and 6 pts Gleason Score > 7. Pretreatment PSAs ranged from 1.75 to 23.88
ng.ml (median 6.95 ng.ml). The treatment regimen consists of a total dose of 38 Gy delivered at 9.5
Gy per fraction, over 4 consecutive days, with > 95% of the PTV encompassed within the prescription
isodose volume. Three gold fiducial markers were placed in prostate gland by the treating urologist using
transrectal ultrasound guidance, and to allow fiducial stabilization and resolution of swelling, prostate
planning study was performed one week after fiducial implantation. Treatment planning was done with CAT
scan fused with Mri in all patients does was prescribed to the 80% isodose line, with 5 mm beyond the
capsule, except posteriorly were the margin was 3 mm. Patients were seen in follow up by the radiation
oncologists or urologist 10 days post-treatment, 1 month later and every 3 months for 2 years with PSA
levels assessed at each follow up. Self administered questionnaire, such as the International prostatic
Symptom Score and the International Index of Erectile Function , was used to better define urinary function
and sexual activities. Toxicity analyses was performed using the Radiation Therapy Oncology Group/
European Organization for Research and Treatment of Cancer (RTOG-EORTC) acute and late radiation
morbidity scoring system.
Results: Acute side effects were generally mild and resolved shortly after treatment. All patients were
placed on A-blockade medication at the beginning of Cyberknife treatment. IPSS scores increased over
the first month of treatment but return to baseline by four months. No rtog grade 4 acute or late ractal/
urinary complications was observed. 2 patients developed late Grade 3 urinary late toxicity following
repeated urological instrumentation, including cistoscopy and urethral dialatation. Three patients, one
with prior Turp, experienced incontinence, two 12 months after the treatment, one 27 months later. One
patient experienced rectal incontinence 12 months after the treatment. The actuarial median follow up
is 30 months (range 12 – 54 months) The patterns of Psa response, show a gradual decline with a psa
nadir below 1.0 ng.ml after 12 months. The four years actuarial psa relapse free survival rate is 95.3% (CI:
89.8%-100.8%) To date all patients are alive, 3 patients failed biochemically. One high risk group patient
developed bone metastases, in 2 intermediate risk group we observed pelvic lympn node involvment.
Conclusions: Early clinical results are encouraging and we conclude that Cyberknife robotic radiosurgery
is a feasible and an emerging non invasive treatment approach to deliver Hypofractionated radiotherapy for
localized prostate cancer. Additional follow up is required to see if these results are durable.
114
P073
HIFU = High intensity focused ultrasound as primary treatment for prostate cancer
D' Hont C.J.L., Van Erps P., Sorber M., Cortvriend J., De Backer T.
ZNA Middelheim, Dept. of Urology, Antwerp, Belgium
Material & Methods: Patients were treated by Ablatherm (EDAP-TMS, Lyon, France) with single HIFU
treatment strategy for their localized prostate cancer in the ZNA Middelheim in Antwerp. Patients with any
previous local therapy for prostate cancer were excluded. Patients were stratified according to D’Amico’s
2003 risk group definitions. Kaplan-Meier analysis was performed to determine biochemical survival with
failure defined according to the 2006 Phoenix definition (nadir+2).
Results: A total of 695 consecutive fully evaluable patients met the inclusion criteria. The average age
was 63.0 В± 7.6 years. Pretreatment PSA was 10,8 В± 7,8 ng/ml, the median Gleason sum was 7 (6 in
56.8%, 7 in 30.7%, 8 and up in11%) and 9,8%, 37,7% and 52,7% of patients were in the low, moderate and
high+T3a risk groups, respectively. 8% T1, 68,2%T2 and 23,3%T3a. Patients were followed for 4.3 В± 2.2
years (range: 1 to 11 years). The median PSA nadir was 0.11 which was reached 14.6 В± 14.2 weeks after
HIFU (67,4% < 0,2 ng/ml, 32,6% 0,2-1ng/ml). Biochemical failure free survival rates at 5, 6 and 7 years are
78%, 75% and 73% respectively. 5YBFSR is 88%,86% and 63% for the low, intermediate and high+T3a risk
groups (p=0,011). A 2nd HIFU treatment is offered in case of bx proven local recurrence (9.2 %). Side
effects are extremely low (3,8% SI gr 1, 5.4% UTI, 6%TUR/BNI, 0,6%AUR). Potency preservation (IFFE-5>20)
is 85%, 55%, 8% in unilateral nerve sparing, full and T3a treatment (outside capsula) groups resp.
Conclusions: HIFU provides good biochemical control through > 7 years of follow-up combined with a
relatively low rate of side effects and meets the results of classical treatments as primary PCA treatment.
Only 1.8% of grade II stress incontinence (no grade III) after 1 month and high rates of potency
preservation are important QuOL factors after cure. With more reliable imaging techniques more focalised
HIFU treatment becomes a possible choice in selected patients. HIFU can be safely repeated and proves
to be a safe salvage treatment in case of local recurrence after any kind of primary treatment, all salvage
treatments remain possible after HIFU.
115
Unmoderated Posters
Introduction & Objectives: HIFU has been the subject of debate for over 10 years as primary treatment
for localized prostate cancer. The objective of this study is to report biochemical and biopsy outcomes
+ Quality of Life of 695 fully evaluable patients treated with HIFU as a primary treatment for T1-T2b/cT3aNxM0 prostate cancer.
P074
Stereotactic body radiotherapy (SBRT) with a focal boost to the visible MRI tumor as
monotherapy for intermediate stage prostate cancer: Early results
Aluwini S.1, Van Rooij P.1, Hoogeman M.1, Praag J.1, Kirkels W.2, Kolkman-Deurloo I.K.1, Bangma C.2
Daniel Den Hoed Oncological Center, Erasmus Medical Center, Dept. of Radiation Oncology, Rotterdam,
The Netherlands, 2Daniel Den Hoed Oncological Center, Erasmus Medical Center, Dept. of Urology,
Rotterdam, The Netherlands
1
Unmoderated Posters
Introduction & Objectives: There is now growing evidence that the prostate cancer (PC) cells more
sensitive for high fraction dose in hypofractionation schemes. The High-dose-rate brachytherapy as
monotherapy is establisched to be an excellent treatment option for PC using extremely hypofractionated
schemes. This can also be achieved with SBRT using the CyberknifeВ®. Here, we report our results on
toxicity and PSA response, using this technique.
Material & Methods: Between June 2008 and November 2011 50 hormone-naГЇve patients with biopsy
proven low to intermediate risk PC underwent SBRT treatment with total dose of 38 Gy in 4 daily fractions
of 9.5 Gy. A boost to 11 Gy a fraction was given on the dominant lesion if visible on MRI. In all patients 4
gold fiducials were implanted in the prostate. One week later a CT-scan and MRI, T1-T2 weighted
sequences were performed to elaborate treatment plan after placement of a Foley catheter to show the
urethra.Toxicity and Quality of life was assessed prospectively using validated questionnaires.
Results: Mean FU was 21 months (range 4-37), median age of the patients was 68 years (range 48-80),
mean initial PSA (iPSA) was 8.2ng/l (range 1.3-16), mean prostate volume was 48 cc (range 22-110).
The clinical T-stages of the patients were: T1c in 60%, T2a in 34%, T2b in 4% and T3a in 2%. The GS was
3+4=7 in 18% of the patients and 3+3=6 in 82%. The MRI staging was: T1c (18%), T2a (44%), T2b (8%),
T2c (4%), T3a (26%). Number of positive biopsies was 1 in 24%, 2 in 22%, 3 in 18%, 4in 16%, 5 in 10% and
7 in 4%. No biochemical failure occurred. Median Nadir PSA was 0.6 ng/ml. In 14 (28%) patients a visible
dominant tumour was detected on the contrast-inhanced MRI, mean tumour volumewas 1.2 cc (0.464.1). Mean dose on tumour area was 47.76 Gy (40.32- 53.82). Median International Prostate Symptoms
Score was 9/35 before treatment, with a median increase of 4, remained stable on 13/35 thereafter. The
EORTC/RTOG toxicity scales showed a grade 2, 3 gastrointestinal (GI) acute toxicity in 12% and 2%,
respectively. The late grade 2, 3 GI toxicity was 3%, 0% during 24 months FU, respectively. Genitourinary
(GU) grade 2 toxicity was seen in 15% in the acute phase, showing a peak of 20% after 12 months,
returning back to 10% at 24 months. A grade 3 GU toxicity was seen in 8% in the acute phase and in 6% in
the period thereafter. No grade 4 toxicity was reported.
Conclusions: This regimen of SBRT for low and intermediate risk prostate cancer patients is well tolerated
with low rate late GI and GU toxicity. Longer FU is needed to confirm this.
116
P075
Extended pelvic lymph node dissection can enhance survival in intermediate and high risk
prostate cancer patients
Alekseev B.Y.1, Nyushko K.M.1, Vorobyev N.1, Krasheninnikov A.A.1, Frank G.A.2, Andreeva Y.Y.2,
Chissov V.I.3, Andrianov A.N.1
Moscow Hertzen Oncology Institute, Dept. of Oncourology, Moscow, Russia, 2Moscow Hertzen Oncology
Institute, Dept. of Pathology, Moscow, Russia, 3Moscow Hertzen Oncology Institute, Director, Moscow,
Russia
Introduction & Objectives: Recent clinical data have established that standard pelvic lymph node
dissection (S-PLND) in prostate cancer (PC) patients is less accurate in assessing lymph node (LN)
metastases then extended (E-PLND). Several studies have demonstrated that E-PLND could enhance
survival, although this question is on the debate because absence of data of randomized studies. The aim
of the study was to evaluate biochemical progression-free survival (PFS) in intermediate and high risk PC
patients who had undergone radical prostatectomy (RPE) and PLND.
Material & Methods: We analyzed a database of 595 patients, who undergone RPE and PLND at the
period since 2006 till 2011 in our institution. 288 consecutive patients with intermediate and high risk PC
(PSA>10 ng/ml, clinical stage ≥T2b, biopsy Gleason score ≥7, percentage of positive biopsy cores ≥50%)
were included in survival analysis. Patient were divided into 3 groups according to the boundaries of PLND:
S-PLND was performed in 39(13.5%) patients; E-PLND – in 137(47.6%) and super extended PLND (SE-PLND)
– in 112(38.9%) patients. LN metastases were verified in 2(5.1%), 26(18.9%) and 38(33.9%) patients
respectively (p=0.003). Patients with LN metastases were excluded from the further survival analysis.
Mean number of LN removed was 13.6В±6.9(4-31); 23.3В±7.2(12-56) and 29.1В±7.9(15-52) respectively
(p<0.0001); mean PSA level was 11.1В±5.6 ng/ml; 13.7В±9.3 ng/ml and 16.4В±10.6 ng/ml respectively
(p=0.04); mean percentage of positive biopsy cores was 43.4В±27.5%; 47.2В±23.9% and 55.2В±27.3%
respectively (p=0.05). Biopsy Gleason score was significantly more favorable in S-PLND group of patients
(p=0.0002). Biochemical recurrence was assessed as elevation of PSA>0.2 ng/ml on three consecutive
measurements.
Results: Median follow up time was 25 months (3-72 months). During this period biochemical recurrences
were observed in 10 (27%) patients in S-PLND group, in 13 (11.7%) patients in E-PLND and in 8 (10.8%)
patients in SE-PLND group. Cumulative 3-year PFS rate was 64.6В±10.1% for patients in S-PLND group,
84.4В±7.7% in E-PLND group and 81.49В±9.9% in SE-PLND group (p=0.035). More extended PLND with
removing >20 LN was associated with significantly increasing PFS rates. Comparing cumulative 38-month
PFS in subgroup of patients with ≤10 and >20 LN removed PFS rates were 36.9% and 76.5% respectively
(p=0.003).
Conclusions: E-PLND and SE-PLND are more accurate for LN staging in PC patients. S-PLND is
associated with worse survival and should not be performed in cases of intermediate and high risk PC.
Extensive E-PLND and SE-PLND with removing > 20 LN could be recommended in this group of patients to
achieve better PFS.
117
Unmoderated Posters
1
P076
Preliminary results of hypofractionated helical tomotherapy for localized prostate cancer
Rivin Del Campo E.1, LГіpez Guerra J.L.2, Matute R.2, Isa N.2, Puebla F.2, Russo M.3, Sanchez-Reyes A.4,
BeltrГЎn C.2, JaГ©n J.2, Marsiglia H.5
Unmoderated Posters
1
Hospital General De Elche. ERESA, Dept. of Radiation Oncology, Elche, Spain, 2Instituto MadrileГ±o De
OncologГ­a/Grupo IMO, Dept. of Radiation Oncology, Madrid, Spain, 3Radiomedicine Institute IRAM, Dept.
of Radiation Oncology, Santiago, Chile, 4Instituto MadrileГ±o De OncologГ­a/Grupo IMO, Dept. of Radiation
Physics, Madrid, Spain, 5Institut De CancГ©rologie Gustave Roussy, Dept. of Radiation Oncology, Villejuif,
Paris, France
Introduction & Objectives: Recent technological advances in radiotherapy have been shown to minimize
complications in surrounding healthy tissue. Hypofractionated schedules may improve biochemical control
while shortening treatment time. The purpose of this study is to evaluate the tolerability of
hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer, and to identify
prognostic factors for toxicity.
Material & Methods: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1T3N0M0) who were treated with hypofractionated HT between August 2008 and July 2011, had no prior
history of pelvic surgery or radiation therapy, and had a minimum follow up of 7 months. All patients
underwent daily megavoltage computed tomography and image-guided verification of the prostate position
prior to treatment. Hypofractionated regimens to the prostate gland and proximal seminal vesicles (SVs)
included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction.
Concurrently, high risk patients received a conventionally fractionated schedule of radiation to the pelvic
lymph nodes (48.6 Gy at 1.8 Gy/fraction) and distal SVs (54 Gy at 2 Gy/fraction). Neoadjuvant androgen
deprivation therapy (ADR) was given to intermediate (N = 20) and high risk patients (N = 12). High risk
patients also received adjuvant ADT. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using
the Radiation Therapy Oncology Group (RTOG) scoring system. Univariate and multivariate analyses were
performed to define predictors for acute and late toxicity.
Results: 32 patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median
age at diagnosis was 69 years (range, 49-87) and the median follow-up 11 months (range, 7-40). The
median rectum volume receiving doses exceeding 60 Gy (V60), 65 Gy (V65), and 70 Gy (V70) were 14%
(range, 5-26), 10% (range, 3-21) and 2% (range, 0-14), respectively. The median bladder V65 and V70 were
12% (range, 3-34) and 3% (range, 0-22), respectively. The volume receiving greater than 50 Gy (V50) of
the femoral heads (left and right) was 0%. Grade 2 acute GI toxicity occurred in 9 patients (19%). No grade
≥ 3 acute GI toxicity was observed. Grade 2 and 3 acute GU toxicity occurred in 9 patients (19%) and 3
(6%) patients, respectively. The incidence of grade 2 late GI and GU toxicity was 4% (N=2) and 2% (N=1),
respectively. No grade ≥ 3 late toxicities were observed. Multivariate analysis showed that patients treated
at 2.6 Gy/fraction or those who received a total radiation dose ≥ 70Gy had higher rates of grade ≥ 2 acute
GU toxicity (P =0.004 and P =0.048, respectively).
Conclusions: Hypofractionated HT in the treatment of localized prostate cancer is tolerated well with no
grade ≥3 late GI and GU toxicities. A higher dose per fraction or radiation dose ≥70 Gy to the prostate is
associated with greater rates of grade ≥ 2 acute GU toxicity. However, this association was not observed
for late toxicity. Further research is needed to assess definitive late toxicity and tumor control outcomes.
118
P078
The first randomised prospective study on the effects of three months neo adjuvant hormonal
therapy in brachytherapy for low and intermediate risk prostate cancer: The NEO-ONE study
Davits R.J.A.M.1, Engelen A.M.2, Van Gils F.3
Tweesteden Ziekenhuis, Dept. of Urology, Tilburg, The Netherlands, 2Instituut Verbeeten, Dept. of Radiotherapy, Tilburg, The Netherlands, 3Maastro Clinics, Dept. of Radiotherapy, Maastricht, The Netherlands
1
Material & Methods: This national multi-centre study is initiated at 3 high volume brachytherapy sites in
the Netherlands and has started at Q2 2012. Inclusion criteria are histological confirmed low or
intermediate risk prostate cancer patients suitable for brachytherapy, prostate volume between 30 and
55 cc, life expectancy 10 years or more. Exclusion criteria include, among others, previous or current
hormonal therapy. The planned enrolment is 400 patients, 200 in each group, calculated using G*power
3.1. We are planning to perform a repeated measures analysis to compare the PSA course between the
2 groups. Assuming a medium effect size ( О±-level 0,05), a desired statistical power of 80% can still be
reached having 20% drop-outs.
Results: The primary end point is PSA course after treatment with a minimal follow-up of three years. The
secondary end point is time to testosterone recovery after cessation of hormonal therapy. Exploratory end
points include prostate volume evaluation after seed implantation and quality of life impacts.
Conclusions: To our best knowledge this is the first randomised trial examining the biochemical effects
of three months Neo Adjuvant Hormonal Therapy in low and intermediate risk prostrate cancer patients
receiving brachytherapy. An outcome in favour of the pre-treated group will justify a larger (international)
survival study with longer follow-up.
119
Unmoderated Posters
Introduction & Objectives: Data from our non randomised observational study suggested a beneficial
biochemical response and a positive effect on major quality of life parameters in patients treated with
three months maximal androgene blockade before low dose brachytherapy for low and intermediate risk
prostate cancer. (Evers, J. , et al. Urology, 2010). These patients were treated for prostate volume reason.
This abstract describes the design of the first randomised study in this aspect; the NEO-ONE study.
P079
Endoplus study – high intensity focused ultrasound (HIFU) approach of early prostate cancer
Manea C.N., Coman I.
EndoPlus Center University of Medicine and Pharmacy Iuliu Hatieganu, Dept. of Urology, Cluj Napoca,
Romania
Unmoderated Posters
Introduction & Objectives: Because of multimodal approach some procedures have improved quality of
life and survival rates for patients with localised prostate cancer. We aim to report the 36 months follow-up
functional and oncological results of high-intensity focused ultrasound (HIFU) in treating localized prostate
cancer and salvage therapy.
Material & Methods: HIFU therapy using the Sonablate 500 TCM was applied to 130 patients with
localized prostate cancer. In 123 cases were scheduled for HIFU in the primary stage and for the other 7
patients, HIFU represented the salvage therapy after radical prostatectomy, external radiotherapy or in 1
case after brachytherapy. The patients were classified according to dВґAmico in: 65 - low risk, 51 - moderate
risk and 14 - high risk. Oncological failure was defined by several criteria, including biochemical failure
(assessed using the Stuttgart definition of the nadir + 1.2ng/ml) or the presence of cancer on biopsy after
treatment.
Results: After performing post procedural serum PSA for all patients after 3 and 12 hours, we found that
the value is 15-25 times higher than the original, as evidence of massive breakdown of prostatic tissue.
Because we wanted to demonstrate the macroscopic effectiveness of HIFU therapy, we performed
urethroscopy in hypopressure for 8 patients who have tissue destroyed by coagulation necrosis. The
mean PSA levels in the primary and salvage groups were 9.8 and 4.6 ng/mL, respectively. The mean HIFU
treatment time in the primary and salvage groups was 115.5 and 75 min, respectively. Using the Stuttgart
definition of biochemical failure, HIFU treatment failed in 11 patients in the primary group (8.6%) and in 2
patients in the salvage group. There were 14 (10.7%) urethral strictures, 10 (7.7%) bladder neck stenosis
cases, 15 (11.5%) erectile dysfunction cases, 5 (3.8%) urinary incontinence cases, 14 (10.7%) urinary
tract infections, 6 (4.6%) orchiepididymitis cases and 12 (9.2%) prostatic carcinoma cases reconfirmed by
transrectal biopsies. No prostatic-rectal fistulae were registered.
Conclusions: HIFU therapy is a desirable procedure for patients who opt for a minimally invasive
therapeutic alternative, with favourable results and minimized complications. Functional results that are
reproducible on a large number of patients and the long period of monitoring are elements supporting the
idea that HIFU procedure is an effective therapeutic strategy in localized prostate cancer and as salvage
therapy when other therapeutic procedures currently available are partially effective. The benefits of
HIFU include reduced risk of post-treatment complications. HIFU exerts its therapeutic effect by inducing
coagulation necrosis in a well-defined area that has been defined before pre surgery. Currently, coagulation
necrosis means pathological cell death, after which the immune response is activated. HIFU seems to
be a promising alternative and a less invasive treatment modality with an encouraging success rate. It is
particularly effective for low- and intermediate-risk patients and it should be considered as an option for
localized prostate cancer. Research carried out (partially) with the financial support of the European Social
Fund - project 8817.5/Sl56949.
120
P080
Castration-refractory prostate cancer – neuroendocrine tumor?
Apolikhin O.I., Sivkov A.V., Keshishev N.G.
Federal State Budget Research Institute of Urology, Dept. of Innovations, Moscow, Russia
Material & Methods: We conducted a pilot study for the visualization of PC in 5 patients with CRPC.
Using a standard gamma camera with a tomographic mode octreotide 111In, (CJSC "Pharm-Synthesis",
Russia) was taken. 27 patients with CRPC were assigned to combination therapy including the prescription
of long-acting somatostatin analogue - octreotide-depo and dexamethasone against the background of
anti-androgen blockade or surgical castration. 20 patients were assigned to combination therapy prior to
the course of systemic chemotherapy (group 1) and 7 patients - after the development of resistance to
taxotere chemotherapy (group 2). PSA was determined in all patients before treatment and once per month
thereafter. ECOG status, pain syndrome on a 6-point scale, tlevel of CgA was measured.
Results: In 4 out of 5 patients, somatostatin receptors have been identified in the primary tumor as well as
in lymph nodes and bones. This result confirms the literature data on the neuroendocrine activity of CRPC.
In average the PSA baseline was 76 ng/ml and 14 ng/ml in groups 1 and 2 respectively. Data analysis
showed that 70% of patients responded to combination therapy by the decrease or stabilization of PSA,
pain release and improved quality of life. In group 1 the regression of the disease was observed in 10
patients (50%), stabilization - in 4 (20%), lack of response - in 6 (30%). In group 2 the response to combination therapy was observed in all 7 patients.
Conclusions: The usage of new methods of CRPC diagnostics and treatment, taking into account the
status of neuroendocrine tumors, allows the optimization of the choice and alternation of adequate
therapeutic approaches. This will provide the achievement of the encouraging clinical results, including
improved quality of patients’ lives and increased time of disease progression.
121
Unmoderated Posters
Introduction & Objectives: An important component in the diagnostics of castration-refractory prostate
cancer (CRPC) is to detect the expression of receptors to somatostatin, as well as to basically define a
biochemical marker of neuroendocrine tumors - chromogranin A (CgA) in blood plasma in comparison with
the performance of PSA. As a non-invasive method to identify the prostate cancer (PC), radioisotope
scanning with the somatostatin analogue - octreotide, labeled with the isotope 111In is used.
P083
Gleason grade at positive surgical margins: A new predictive factor for recurrence after radical
prostatectomy
Benchikh El Fegoun A.1, Choudat L.2, Doizi S.1, Hermieu J.F.1, Dominique S.1, Hupertan V.1, Ravery V.1
Hopital Bichat Claude Bernard, University Paris VII, APHP, HUPNVS, Dept. of Urology, Paris, France,
Hopital Bichat Claude Bernard, University Paris VII, APHP, HUPNVS, Dept. of Pathology, Paris, France
1
2
Unmoderated Posters
Introduction & Objectives: To establish predictors of biochemical recurrence by analysing the
pathological characteristics of positive surgical margins (PSM), including Gleason grade of the carcinoma
at the involved margin in order to select patients for adjuvant radiation therapy.
Material & Methods: Retrospective evaluation of patients managed between 1995 and 2010 in a single
academic center. 186 patients with PSM were included in this study. Patients with pT3b and pT4 cancers
where excluded. Kaplan-Meier analyses were performed to examine the relationships between clinicopathological variables and biochemical recurrence-free survival (BRFS). A decision curve analysis was
performed to assess the value of Gleason grade at margins added to other clinical and pathological
variables.
Results: Median follow-up was 36 months (15-66), 81 patients recurred after a median of 24 months
(9-46). 5 years BRFS was 65% and 45% (OR=1.9; p=0.004) for patients with Gleason grade 3 and ≥4 at
margins. For patients with PSM <3 and ≥3mm, 5 years BRFS was 68% and 38% (OR=2.5; p=0.0005). On
multivariate analysis PSA (p=0,01), clinical stage (p=0,03), Gleason score on the specimen (p=0,02), the
number (p=0,02), the length (p=0,002), and the Gleason score at the PSM (p=0,05) where independent
predictors of recurrence. The best model to predict 5 years BRFS included PSA, length and Gleason grade
at margins (graph1). Graph 1: Decision curve analysis comparing 3 models: model 1 (PSA, clinical stage,
Gleason score on the specimen), model 2 (PSA, length of PSM, Gleason grade at PSM) and model 3 (PSA,
length of PSM).
Conclusions: Gleason grade at PSM is an independent prognostic factor of recurrence after radical
prostatectomy. The use of a predictive model including PSA, the length of PSM and Gleason grade at PSM
will help to better select patients at higher risk of recurrence who will benefit of adjuvant radiation therapy.
122
P084
Histoscanning in monitoring of patients after prostate HIFU-ablation
Glybochko P.V., Alyaev Y.G., Amosov A.V., Krupinov G.E., Ganzha T.M., Obuhov A.A.
First Moscow State Medical University, Dept. of Urology, Moscow, Russia
Material & Methods: Since September 2011 histoscanning was performed in 90 patients who have been
previously (in terms from 1 year to 7 years) HIFU-therapy for localized prostate cancer. Histoscanning was
performed using a diagnostic system, which consists of an ultrasonic apparatus Pro Focus 3D Professional
2202 (BK Medical), 8818 probe, magnetic sensor and the rotator signal processing computer system
"Histoscanning". The list included the DRE, PSA, PSA doubling time, PSA velocity increment, TRUS with
color and power Doppler mapping, dynamic magnetic resonance imaging of the pelvis with contrast
enhancement and the use of rectal coils. Patients were divided into three groups depending on the amount
of the identified areas suspicious for malignancy: 1 (51 people) - less than 0.2 cm3, 2 (24 people) - from
0.2 cm3 to 0.5 cm3, and 3 (15 people) - more than 0.5 cm3. On the basis of suspicious areas of the map
all the patients underwent biopsy with subsequent histological verification and comparison of data.
Results: Prostate volume ranged from 3 to 25 cm3, PSA of 0.2 to 6.1 ng / ml. In the first group of
patients with biopsy of suspicious areas are obtained histologically necrotic tissue, and sclerotic changes.
In the second group - in some patients was obtained including the tumor tissue. In the third group of
patients histologically confirmed the presence of recurrent disease. In assessing the false positive and
false negative results when comparing histoscanning data and histologic conclusions in the first group
sensitivity of histoscanning was 100%, specificity of 8% in the second group - 96% and 87.5% in the third
group - 100% and 100% respectively.
Conclusions: Histoscanning relatively inexpensive, safe and noninvasive method for the study, the ability
to localize foci of prostate cancer volume of 0.2 cm3 with a high degree of sensitivity and specificity.
Smaller volume of 0.2 cm3 to be regarded as clinically insignificant with respect to the presence of
recurrent disease. Given the small size of the foci, is not ruled out the error of aiming at performing a
biopsy, which definitely does not refute the data obtained by histoscanning. The sensitivity of this technique
is much higher than the existing routine methods of examination, and reaches 100%. In monitoring patients
after HIFU-therapy histoscanning showed a high degree of accuracy in detecting disease recurrence.
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Unmoderated Posters
Introduction & Objectives: Prostate cancer is now regarded as one of the most serious health problems
among the male population. Improved diagnosis has allowed to identify prostate cancer at an early stage,
which led to the introduction into clinical practice a wide range of focal surgical treatment methods that
aim to achieve disease control without a significant loss in quality of life. However, it still remains the
problem of monitoring in the postoperative period, related to the imperfection of the existing methods of
assessment and adequate visualization of the tumor process. In our opinion a promising solution to these
issues is histoscanning.
P085
Risk factors of low quality of life in patients in active surveillance
Bellardita L.1, Alvisi M.F.1, Rancati T.1, Magnani T.1, Catania S.1, Marenghi C.1, Nicolai N.2, Salvioni R.2, Villa
S.3, Valdagni R.4
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept of. Prostate Cancer Program, Milan, Italy,
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept of. Urology, Milan, Italy, 3Fondazione IRCCS Istituto
Nazionale Dei Tumori, Dept of. Radiation Oncology 1, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale Dei
Tumori, Dept of. Prostate Cancer Program, Radiation Oncology 1, Milan, Italy
1
Unmoderated Posters
2
Introduction & Objectives: The potential anxiety and psychological distress that could stem from
observational management of prostate cancer (PCa) are still debated. Studies showed that patients who
choose Active surveillance (AS) report similar or higher levels of Health-Related Quality of Life (HRQoL)
compared to patients who choose prostatectomy, radiotherapy or brachiterapy. Nonetheless, a minority
of patients report some level of psychological distress. The aim of this study is to evaluate the individual
factors that can be associated with the risk for AS patients to experience low levels of HRQoL.
Material & Methods: Between Nov 2007 and Jan 2012, 95 PRIAS patients completed at 10-month followup (T1) the following questionnaires: a) semi-structured interview, used to collect demographic features,
personal experiences and motivation to enter AS (administered at entrance - Time 0); b) Functional
Assessment of Cancer Therapy – Prostate Version (FACT-P), measuring HRQoL; subscales: physical, social,
emotional, functional and wellbeing related to prostate cancer symptoms. c) Mini Mental Adjustment
to Cancer scale (Mini-MAC), assessing adjustment to cancer, subscales Fighting Spirit, Helplessness/
Hopelessness, Anxious Preoccupation. A global score (Q-score, see Barnet et al. 2011) was calculated
for both FACT-P (Q-FACT-P) and Mini-MAC (Q-ADJ) for Time 1. The 25th percentile was used as cut-off, i.e.
scores below 25th percentile=low score, above 25th percentile=normal score. Kruskall-Wallis test was
performed to evaluate the associations between demographic features, personal experiences, motivation
to enter PRIAS and adjustment to cancer on one side and HRQoL on the other side. Logistic regression was
performed to evaluate the variables that increased the risk of low HRQoL at 10 month-follow up.
Results: Kruskall-Wallis test showed several significant correlations between demographic features,
personal experiences, motivation to enter PRIAS and adjustment to cancer and HRQoL. Amongst these,
the ones that contributed to the best model were: a) the presence of a partner which was correlated
with high SWB score (mean ranks 24.63 vs 42.26, p = 0.0410); b) presence of comorbidities which was
correlated with low PWB score (mean ranks 44.24 vs 34.89, p = 0.0381). The variables included in the
best multivariate logistic model for HRQoL at Time 1 (total p=0.0002) were: Q-ADJ (continuous variable
OR=0.54, p=0.0018), PSA (continuous variable, OR=1.17, p=0.4311), presence of partner (OR=0.15,
p=0.0484), presence of co-morbidities (OR=0.21, p=0.0594). The rock curve for the model is showed in
Figure 1 (AUC= 0.753, 95%CI: 0.654-0.836).
Conclusions: A negative style of adjustment to the idea of living with (“untreated”) cancer is associated
with the risk of experiencing low HRQoL. Patients may have protective factors such as the presence of a
partner (which decreases the risk of having low HRQoL). Patients entering AS protocols could be helped
to clarify how they are dealing with their cancer and whether they have the psychological and emotional
124
Unmoderated Posters
support they may need in order to prevent the risk of impairment in their quality of life following cancer
diagnosis and observational management of PCa. Acknowledgments to: Prostate Cancer Program
Multidisciplinary Clinic Team at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Foundations I.
Monzino and ProADAMO.
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P086
Post-radical prostatectomy incontinence: Patient perceived outcomes after the advance male
sling procedure
Rijo E., Bielsa O., Lorente J.A., Ubre A., Frances A., Pino L., Nohales G., Arango O.
Hospital Del Mar, Dept. of Urology, Barcelona, Spain
Unmoderated Posters
Introduction & Objectives: The artificial urinary sphincter is the gold-standard treatment for post-radical
prostatectomy (RP) stress urinary incontinence (SUI). The AdVance represents a treatment option. There
are only a few studies that determine the patient perceived effectiveness after the procedure.
Material & Methods: 43 Advance slings were placed for the treatment of post-RP SUI. A retrospective
review of 32 patients with a follow-up 5 question telephone-survey performed in March-2012. Consisted
of 2 validated questions pertaining to patient satisfaction: patient global impression of improvement(PGI-I)
and the patient global impression of severity(PGI-S) along with 2 additional questions pertaining to number
of pads/day(PPD) used, and whether or not the patient would recommend the procedure to a friend.
Results: A cure rate (no pads or one dry security pad) of 65%, an improved rate(1-2 pads or pad reduction≥50%) of 21%, and 14% of failure rate were observed at 3 months postprocedure. Telephone surveys
were administered a mean of 30-months after the procedure and 32 patients were contacted (11 patients
were lost to follow-up). Based on the PGI-I, 30% of the patients responded that their incontinence was
very much better and 15% much better. Additionally, 70% of patients said that they would recommend this
procedure to a friend. The high subjective failure rates presented are also due to patient selection. Some
patients presented with severe incontinence.
Conclusions: The ideal candidate for this procedure is a patient with mild to moderate SUI without history
of radiotherapy treatment. Unfortunately our data show discouraging results; patients are using more pads
for incontinence and the procedure not demostrate durable results over-time.
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P087
Use of a standardized total average toxicity score in a population of prostate cancer patients
radically treated with radiotherapy: Correlation with clinical and dosimetric risk factors and
determination of the exceptionally radio-sensitive cohort
Morlino S.1, Rancati T.2, Tomatis S.3, Fiorino C.4, Fellin G.5, Vavassori V.6, Cagna E.7, Gabriele P.8, Girelli G.9,
Mauro F.A.10, Valdagni R.11
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Radiotherapy, Milan, Italy, 2Fondazione IRCCS
Istituto Nazionale Dei Tumori, Prostate Cancer Program, Milan, Italy, 3Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Medical Physics, Milan, Italy, 4Istituto Scientifico San Raffaele, Dept. of Medical
Physics, Milan, Italy, 5Ospedale Santa Chiara, Dept. of Radiotherapy, Trento, Italy, 6Humanitas Gavazzeni,
Dept. of Radiotherapy, Bergamo, Italy, 7Ospedale Sant'Anna, Dept. of Radiotherapy, Como, Italy, 8IRCC,
Dept. of Radiotherapy, Candiolo, Italy, 9Ospedale ASL 9, Dept. of Radiotherapy, Ivrea, Italy, 10Ospedale Villa
Maria Cecilia, Dept. of Radiotherapy, Lugo Di Romagna, Italy, 11Fondazione IRCCS Istituto Nazionale Dei
Tumori, Prostate Cancer Program and Dept. of Radiation Oncology 1, Milan, Italy
Introduction & Objectives: Standardized Total Average Toxicity (STAT) score was proposed by Barnett
et al. (Int J Radiat Oncol Biol Phys 2011) as a global score which may be used to (a) facilitate the analysis of
overall late radiation toxicity (tox), (b) pool data from multiple trials (in order to increase statistical power)
and (c) select patients (pts) to be included in studies of possible genetic determinants of radiotherapy (RT)
tox.In the same paper application of STAT to two cohorts of breast cancer pts was presented. We here
evaluate application of STAT to the AIROPROS 0102 prostate cancer population, with the aim of verifying
that STAT keeps all known correlations of single tox endpoints with clinical/dosimetric risk factors and of
selecting possible radio-sensitive and radio-resistant patients (pts).
Material & Methods: In the AIROPROS 0102 trial (RT doses: 70-80Gy, 1.8-2Gy/fr) rectal tox was recorded
through self-reported questionnaires involving 15 questions on the rectal syndrome. STAT calculation were
made following definition reported by Barnett et al. Key point is that STAT defines whether a pt’s global tox
is high or low relative to the distribution of the global tox of other pts. STAT measures the distance between the single pt and the average of all considered pts in terms of standard deviations. Three STATs were
here considered: baseline STAT (BSTAT, 1124pts), acute STAT (ASTAT, 1123pts) and late (3yrs follow-up)
STAT (LSTAT, 646pts).We considered pts with LSTAT>0.8 as exhibiting high tox with respect to the whole
study cohort and clinical/dosimetric predictors of LSTAT>0.8 were determined through multivariable
logistic analysis.Analysis of residuals was used to individuate the radio-sensitive and radio-resistant cohorts.
Results: ASTAT and BSTAT were highly correlated: in the group of pts with BSTAT<1 median ASTAT was
-0.2 vs 0.7 for pts with BSTAT>1 (p<0001, Mann-Whitney test). LSTAT was correlated to both BSTAT and
ASTAT (p=0.02 and p=0.0001 respectively). LSTAT>0.8 (43/646pts) was predicted by: BSTAT (continuous
variable, OR=2.01, p=0.04), previous diseases of the colon (OR=3.04, p=0.02), the percent volume of
rectum receiving more than 40Gy (V40Gy, continuous variable, OR=1.02, p=0.08) and the percent volume
of rectum receiving more than 75Gy (V75Gy, continuous variable, OR=1.05, p=0.03). Overall p=0.0006,
AUC of the modelis 0.74.From analysis of residuals, 14 pts emerged as possible radio-sensitive pts (pts
with high LSTAT which is not predicted from model) and 7 pts as possible radio-resistant pts (pts with low
LSTAT which is in contrast with model prediction).
Conclusions: Correlation between high LSTAT and clinical/dosimetric risk factors confirmed previously
results, found in AIROPROS 0102 trial, for the single tox endpoints (late rectal bleeding and late fecal
incontinence, see Fellin 2009, Valdagni 2012 and Fiorino 2012).This global approach allows pooling of data
from different trials (increasing statistical power of analysis) and identification of pts whose scores are
not explained by the global model and who may be included in studies of possible genetic determinants of
radiotherapy tox.
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Unmoderated Posters
1
P088
Nerve sparing HIFU as primary “focalized” treatment for localized prostate cancer:
A single center study of 158 man with 7 years of follow up
D' Hont C.J.L., Van Erps P., Sorber M., Cortvriend J., De Backer T.
ZNA Middelheim, Dept. of Urology, Antwerp, Belgium
Unmoderated Posters
Introduction & Objectives: Nerve Sparing HIFU has been the first Focal strategy for prostate cancer. The
objective of this study is to report biochemical and biopsy outcomes of 158 patients after unilateral nerve
sparing HIFU as a primary treatment for T1c-T2b/c prostate cancer (largest nerve sparing HIFU series ever
reported).
Material & Methods: Patients treated by Ablatherm (EDAP-TMS, Lyon, France) with single unilateral Nerve
Sparing HIFU treatment strategy for their localized prostate cancer in the ZNA Middelheim in Antwerp.
Patients with any previous local therapy for prostate cancer were excluded. Only patients with unlateral
negative lateral biopsies were included for unilateral nerve sparing HIFU. Patients were stratified according
to D’Amico’s 2003 risk group definitions. Kaplan-Meier analysis was performed to determine biochemical
survival with failure defined according to the 2006 Phoenix definition (nadir+2).
Results: A total of 158 consecutive patients met the inclusion criteria. The average age was 60.0 В± 7.1
years. Pre treatment PSA was 9.3 В± 6.4 ng/ml, the median Gleason sum was 7 and 17.7%, 49.4% and
32.9% of patients were in the low, moderate and high risk groups, respectively. Patients were followed
for 4.3 В± 2.2 years (range: 1 to 9 years). The median PSA nadir was 0.11 which was reached 15.7 В± 15.1
weeks after HIFU. Biochemical failure free survival rates at 5, 6 and 7 years are 80%, 74% and 70%
respectively. A 2nd HIFU treatment is offered in case of bx proven local recurrence (10,1 % - most in the
preserved untreated area). Side effects are extremely rare, data are reported in the table. Only 1.3% of
grade I stress incontinence (no grade III) and a potency preservation of > 85 % (63.3% without any medical
support - IIEF-5 > 22). In case of bilateral nerve sparing HIFU ( all lateral biopsies negative ) > 98% of
patients can preserve their potency (10 pts) - after a full HIFU treatment potency preservation is possible in
> 50 % of patients (658 pts in our study).
В Unilateral Nerve Sparing (n=158)
Incontinence, % (n)
Stress 1
Stress 2
Stress 3
Urge
1 mth afterHIFU
3.8% (n=6)
1.3% (n=2)
0% (n=0)
1.3% (n=2)
6 mnths after HIFU
1,3 % (n=2)
0%
0%
0%
Potency, % (n)
Impotent
Fully Potent without aids
Fully Potent with aids*
Diminished without aids
Diminished with aids aids*
14.6% (n=23)
61.4% (n=97)
20.9% (n=33)
1.9% (n=3)
1.3% (n=2)
IIEF-5 score
<7
22-25
12-22 without aids
17-22
12-22 with aids*
* Use of PDE-5 Inh = choice of patient
Total potency preservation
> 85 %
Infection, % (n)
5.1% (n=8)
Other
TUIP, % (n)
Bladder sclerosis, % (n)
Stricture, % (n)
Retention, % (n)
pos. bx during follow up
2.5% (n=4)
1.3% (n=2)
0.6% (n=1)
0.6% (n=1)
10,1% (n=16) = second HIFU
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Unmoderated Posters
Conclusions: Nerve sparing HIFU provides good biochemical control through > 7 years of follow-up
combined with a relatively low rate of side effects = excellent QuOL and good cancer controll. With more
reliable imaging techniques more focalised HIFU treatment becomes a possible and safer first choice
treatment in patients with limited and more focalized prostate cancer concerned about their Quality of Life
after treatment, knowing that in case of a local recurrence all salvage options ( 2nd HIFU & all others ) still
remain possible.
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P089
Patients’ decision-making process towards the choice of active surveillance
Bellardita L.1, Donegani S.1, Magnani T.1, Salvioni R.2, Villa S.3, Valdagni R.4
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Prostate Cancer Program, Milan, Italy,
Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Urology, Milan, Italy, 3Fondazione IRCCS Istituto
Nazionale Dei Tumori, Dept. of Radiation Oncology 1, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale
Dei Tumori, Dept. of Prostate Cancer Program, Radiation Oncology 1, Milan, Italy
1
2
Unmoderated Posters
Introduction & Objectives: Active Surveillance (AS) may represent for selected patients with low risk,
potentially indolent prostate cancer (PCa) a viable alternative to radical therapies, thus reducing the risk of
over-treatment. Researchers and clinicians emphasized that the choice of AS may be a controversial one
as patients have on one side the chance to avoid the side effects of radical therapies and on the other the
burden of living with an untreated PCa. The aim of our study is to focus on the decision-making process
leading patients to elect AS amongst different therapeutic options.
Material & Methods: An observational, qualitative study was conducted. Between 2007 and 2009, 46
patients (mean age 67 years) were administered a semi-structured interview at enrolment in the Prostate
cancer Research International: Active Surveillance protocol. The focus of the interview was on the first
question, i.e. “Why did you choose AS?”. Interviews were audio-recorded and verbatim transcriptions made.
Content analyses were performed by using a text-driven, automatic software which allows meaningful
patterns of themes to emerge (T-lab).
Results: Four clusters of themes emerged. In cluster 1, labeled as The Start, the most meaningful theme
was the ambivalence in front of different therapeutic options (example, “If there were no side effects I
would have gone for surgery; you have everything removed and you do not think about it anymore. But,
well, it seems that the sexual complication is the more likely and also incontinence”). In cluster 2, The
Crossroad, the focus was on patients’ assessment of the aggressiveness of their PCa (“I chose AS because
from what I understood, from what I was told, it’s not a severe thing. It’s something that needs to be kept
under control. Not aggressive). In cluster 3, The Map, the topic was the collection of information from
specialists (“You can do what you prefer but I can tell you that the side effects of each therapy that you will
decide to undergo will make things worse compared to your actual state”). In cluster 4, The Encounters,
the main theme was the collection of data through informal sources (“I signed up for the surgery waiting
list before a friend of mine told me Wait, if you are not convinced you talk to the oncologist, it’s still at the
beginning, do not hasten, wait, in the meanwhile whether it should develop you gained some years”).
Conclusions: Patients go through a complex decision-making process that can be compared to the tale
of a journey, often not only a metaphorical one, during which they actively search for formal and informal
data. People that they meet highly contribute to their choice. Patients are motivated to opt for AS based on
the subjective evaluation of a number of factors including medical information as well as characteristics of
their psycho-social context. Understanding motivation for AS will help clinicians support patients in making
the best choice for them, thus avoiding potential future regret. Acknowledgements to: Prostate Cancer
Program Multidisciplinary Clinic Team; Foundations I. Monzino and ProADAMO ONLUS.
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P090
Complications of brachytherapy in the complex treatment of prostate cancer
Kaprin A.D., Semin A.V.
Peoples’ Friendship University of Russia, Dept. of Urology With Class Oncourology, Moscow, Russia
Material & Methods: We have examined 270 patients undergoing brachytherapy for prostate cancer
in the period from 2003 to 2009, median follow-up was 2.8 years. Brachytherapy patients was carried
out both as an independent method with dose 140 Gy (n = 207, 76.7%), as well as the first step in the
combined radiation therapy with dose 110 Gy (n = 63, 23.3%). Symptoms were evaluated after interstitial
radiation therapy after 2 weeks, 1, 3, 6 and 12 months. To assess the symptoms of an international
system of counting used by the symptoms of prostate cancer (IPSS), as the objective measures used
urodynamics and prostate volume.
Results: The largest group of complications were irritative symptoms such as pollakiuria and urgency to
urinate, pain, discomfort and burning sensation when urinating. They were present in 53,7+4,7% of patients
in the combined radiotherapy group and 68,6+2,3% in the second group in the early postimplantation
period. After 1 month, with an overall increase in the severity of symptoms in a group of combined
radiation therapy were significantly lower than the last 63,7+1,2% versus 95,7+2,6% in the brachytherapy
group, p <0.05. The difference between the two groups is due to the difference in dose, as well as a
smaller number of needles and sources used for implantation. Obstructive symptoms can also occur as
a result of stricture bulbo-membranous and prostate urethra caused by the implantation of grains in per
apical area. In our study, obstructive symptoms occurred in 27+2,3% in both groups and expressed in the
reduction of peak rate of urination and increased residual urine volume. Observed symptoms in the early
postimplantation period and were associated with swelling of the prostate as a result of injuries in the
process of introducing needle. 94,6+4,7% of patients with obstructive symptoms developed, the volume of
the prostate gland before the procedure exceeded 43 cm3.
Conclusions: We have considered only some of the factors, such aspects as technique of implantation,
the sources of their activity was not analyzed in this study. Multivariate analysis will expand the
understanding of complications after brachytherapy. Timely and rational evaluation of all factors in the
complex allows you to select the optimal method of treatment and minimize potential complications.
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Unmoderated Posters
Introduction & Objectives: Brachytherapy for prostate cancer is becoming more and more popular
method of treating prostate cancer (PCa). The escalation of the dose was a significant factor in the
success of radiotherapy in the treatment method for prostate cancer. Brachytherapy is used as a
permanent implant sources of low dose rate (LDR) or temporary introduction high dose rate sources (HDR).
This method of treatment used in patients with prostate cancer formation in low-risk and intermediate
rare. However, should not be considered absolutely safe for brachytherapy techniques. Based on the
localization, complications can be divided into two main groups. This is a complication associated with
intestinal lesions and complications of the lower urinary tract.
P091
Predictors of international prostate symptom scores (IPSS) worsening at the end of high-dose
radiotherapy for prostate cancer: First results of a large prospective cohort study (DUE-01)
Cozzarini C.1, Carillo V.2, Villa S.3, Degli Esposti C.4, Girelli G.5, Muraglia A.6, Rancati T.7, Vavassori V.8,
Valdagni R.9, Fiorino C.2
Istituto Scientifico San Raffaele, Dept. of Radiotherapy, Milan, Italy, 2Istituto Scientifico San Raffaele, Dept.
of Medical Physics, Milan, Italy, 3Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Radiotherapy,
Milan, Italy, 4Ospedale Bellaria, Dept. of Radiotherapy, Bologna, Italy, 5Ospedale ASL 9, Dept. of Radiotherapy, Ivrea, Italy, 6Arcispedale S. Maria Nuova, Dept. of Radiotherapy, Reggio Emilia, Italy, 7Fondazione
IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program, Milan, Italy, 8Humanitas Gavazzeni, Dept. of
Radiotherapy, Bergamo, Italy, 9Fondazione IRCCS Istituto Nazionale Dei Tumori, Prostate Cancer Program
and Dept. of Radiation Oncology 1, Milan, Italy
Unmoderated Posters
1
Introduction & Objectives: DUE-01 is a prospective observational study aimed at developing predictive
models of genito-urinary (GU) toxicity and erectile dysfunction (ED) after high dose (<70Gy) radiotherapy
(RT) for prostate cancer. GU and ED are assessed through the following 5 validated questionnaires: a)
EORTC QLQ-C30; b) IPSS; c) ICIQ-SF; d) IIEF; e) Dyadic adjustment scale.The aim of the present analysis
was to find correlation between clinical/dosimetry parameters and IPSS changes between baseline and
radiotherapy end (О”IPSS).
Material & Methods: IPSS was administered to the patients before and at the end of the therapy. Many
clinical variables were prospectively collected including: stage, concomitant morbidities, hormonal
therapy, previous surgery, smoking, age, BMI. The correlation with О”IPSS and IPSS at the end of the
therapy was tested by the Spearman test in the whole population and in the sub-group of patients with
baseline IPSS<15. IPSS≥15 at the end of RT was also considered as an endpoint: logistic uni- and stepwise
multivariate (MVA) analyses were performed.
Results: Complete data of 153 patients (6 Institutes) were available, including baseline and end RT
questionnaire. ∆IPSS was on average +4.4(±7.2). Average ∆IPSS were +5.0 (p<0.0001) and -0.4 (p=0.86)
for the patients with basal IPSS<15 and IPSS≥15, showing that IPSS changes mainly occur in the group
with low basal IPSS. ∆IPSS and IPSS at the end of the therapy were mainly correlated with basal IPSS
(spearman p=0.01), use of anti-hypertensive (p=0.06), age (0.01) and daily dose (0.06). The figure
shows the impact of hypertension on end-RT IPSS, both in the whole population and in the sub-group of
patient with low basal IPSS.The risk of IPSS≥15 at the end of radiotherapy (52/153 patients, 34%) may
be predicted by a 5-variable logistic model (overall p<0.0001, AUC=0.75) including basal IPSS (OR=1.14,
p=0.0007), use of anti-hypertensive (OR=3.5, p=0.005), hypofractionation (2.5-2.7 vs 1.8-2.0 Gy/fr,
OR=2.8, p=0.018), T stage (T2-3 vs T1, OR=2.2, p=0.05) and age (continuous, protective, OR=0.92,
p=0.02). The same variables (except basal IPSS) were included in another model, considering only patients
with basal IPSS<15 (AUC: 0.72).
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Unmoderated Posters
Conclusions: A model predicting the risk of IPSS≥15 at the end of the therapy has been developed based
on a prospective, cohort study. In particular, hypertension is an important predictor. The next addition of
bladder dose-volume/surface information is expected to further improve our knowledge on the prediction
of acute GU symptoms.
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P092
Metabolic changes in citrate and spermine concentrations can predict prostate cancer
aggressiveness
GiskeГёdegГҐrd G.1, Bertilsson H.2, Selnaes K.1, Wright A.3, Bathen T.1, Viset T.4, Halgunset J.5, Angelsen A.2,
Gribbestad I.1, Tessem M.1
NTNU, MI Lab, Trondheim, Norway, 2St. Olavs University Hospital, Dept. of Urology, Trondheim, Norway,
University Nijmegen Med Center, Dept. of Radiology, Nijmegen, The Netherlands, 4St. Olavs University
Hospital, Dept. of Pathology/Genetics, Trondheim, Norway, 5NTNU/St. Olavs University Hospital, Dept. of
Pathology/Genetics, Trondheim, Norway
1
3
Unmoderated Posters
Introduction & Objectives: Currently there are no accurate diagnostic tools for discriminating aggressive from harmless prostate cancers. In this study, ex vivo magnetic resonance spectroscopy (MRS) was
used to provide the metabolite profiles of prostate cancer and normal adjacent tissues. The purpose was
to identify biomarkers for prostate cancer aggressiveness.
Material & Methods: Using a new harvesting method (Bertilsson 2011), high quality prostate tissue
samples (n=162 samples, 48 patients) were obtained from normal tissue and cancer tissue with different
Gleason scores (score 6-9, where 9 is the most aggressive) and analyzed by HR-MAS MRS (Bruker avance
DRX600). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine
the metabolic changes and predict cancer aggressiveness by comparing normal, low grade (Gleason
score=6) and high grade (Gleason score≥7) cancers. The multivariate models were validated by double
cross-validation, and differences in metabolite concentrations were examined using linear mixed models.
Results: Based on the metabolite profiles, normal tissue, low grade and high grade tissue were discriminated with a classification accuracy of 85%, 66% and 77%, respectively, using PLS-DA. Out of 23 quantified
metabolites, 17 metabolites were significantly changed in cancer samples compared to normal adjacent
tissue. The metabolite profiles could be related to Gleason score (r=0.71) by PLS analysis. High grade
cancer tissues were distinguished from low grade cancer tissues by decreased concentrations of spermine
(p=0.0044) and citrate (p=7.73В·10 -4).
Conclusions: HR-MAS MRS provides detailed metabolite profiles distinguishing cancer and normal
adjacent tissues. The metabolite profiles are related to prostate cancer aggressiveness, and spermine and
citrate are promising biomarkers for separating indolent from aggressive prostate cancers. HR-MAS MRS
can be used as an additional diagnostic tool, and the results support the benefit of MRS in future in vivo
investigations of prostate cancer patients. ReferencesBertilsson et al (2011) The Prostate 71: 461-469.
134
P093
Prevalence of prostate cancer in Ghana
Egote A.K., Nana N.O.
Regional Hospital, Sunyani, Dept. of Urology, Sunyani, Ghana
Material & Methods: From February 2009 to February 2011 two hundred and four patients who had PSA
of 4ng/ml and above were counselled for transrectal ultrasound guided biopsies. Total of 10 to 12 prostate
cores tissue were biopsed for histopathology. Lignocaine 2% jelly was used as transrectal local aneasthesia. Prophylasis antibiotic ciprofloxacin 500mg BD X 5 days was prescribed starting a day before biopsy.
Five cores are biopsed from each periphery of the prostate lobe, then two cores from suspected areas.
The procedure was strictly done under aseptic condition.
Results:
PSA(ng/ml)
patients
BPH
Ca prostate
4-4.9
52
44(88.46%)
6(11.543%)
10-19.9
56
36(64.29%)
20(35.71%)
20-49.9
56
26(46.43%)
30(53.57%)
50-100
26
8(30.77%)
18(69.23%)
above 100
14
4(28.57%)
10(71.43%)
total
204
118
84
Table 1: from table 1 the higher the PSA value the higher the percentage of cancer formation. 41.2% out 204 patients had prostate
cancer. 57.8% had benign disease.
Age(years)
# patients with Ca Prostate
percentage
40-49
4
4.76%
50-59
12
14.29%
60-69
18
21.43%
70-79
24
28.57%
80& above
26
30.95%
total
84
100%
Table 2: Age increases with high risk of prostate cancer
Conclusions: Prostate cancer forms 41.2% of all prostatic diseases in the Ghanaian male population.
Prostate cancer cases increases as man grows older in the Ghanaian population.prostate cancer is the
most killer disease among male population in Ghana. Prostate cancer is late detected in the Ghanaian
population due to lack of voluntary screening.
135
Unmoderated Posters
Introduction & Objectives: Prostate cancer stands second place among cancer diseases in the USA and
fourth worldwide. Due to lack of available statistics prostate cancer was less known in Africa. However,
recent data available shows that prostate cancer is the most killer male cancer in Nigeria and Uganda.
Since the introduction of prostate specific antigen(PSA) screening more patients are beeing diagnosed
early for curative treatment. However, in Ghana more patients are beeing diagnosed at late stage of the
disease due to lack of voluntary screening. Objective: To know the incidence of prostate cancer in Ghana.
P094
Towards effective chemotherapy regimens for docetaxel resistant prostate cancer
Lundon D., Prencipe M., O'neill A., Fitzpatrick J., Watson W.
University College Dublin, School of Medicine and Medical Sciences, Dublin, Ireland
Unmoderated Posters
Introduction & Objectives: Docetaxel (TaxotereВ®) is the most effective chemotherapeutic agent for the
treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the
treatment of these patients is docetaxel resistance. Defining the mechanisms of resistance so as to inform
subsequent treatment options and combinations represents a challenge for clinicians and scientists alike.
Experiments and publications in our laboratory have shown complex changes in pro and anti-apoptotic proteins in the development of resistance to Docetaxel. Targeting these changes individually do not significantly impact on the resistant phenotype but understanding the central signalling pathways and transcription
factors which control these could represent a more appropriate therapeutic targeting approach.
Material & Methods: We have developed a number of Doxetaxel resistant sublines in PC-3, and undertaken a transciptomic analysis of these cells by DNA microarray analysis using the Affymetrix Human
Gene 1.0 ST Array. Using novel bioinformatic techniques, including correspondence, between-group and
co-inertia analyses, we have predicted a number of new targets for suitable for manipulation in metastatic
castrate resistant prostate cancer.
Results: Our generated list of transcription factors includes HSF1, TR4, VDR-RXR, SRF and ESR1, which
are predicted to be responsible for the differential gene expression observed in Docetaxel resistance. We
have mapped the cell-processes of these transcription factors and can display how they are intimately implicated in regulating docetaxel resistance in Prostate Cancer Cell lines. We have demonstrated the close
interplay of these on apoptosis, response to stress, chemotaxis and chemosensitivity amongst a myriad
of inveigling functions. We are currently manipulating the expression and activity of these transcription
factors, using a siRNA approaches to validate their roles in the apoptotic resistance to Docetaxel and
investigating their expression in patient tissue micro arrays of metastatic and Docetaxel resistant disease.
Conclusions: Due to the complexity of changes associated with the development of resistance to
Docetaxel, manipulating the upstream transcription factors may represent a more comprehensive
therapeutic targeting approach for this advanced form of prostate cancer.
136
P095
Defining patient-specific rectal and bladder dose constraints for stereotactic body radiation
therapy of the prostate: An evidence-based method
Carrara M.1, Morlino S.2, Descovich M.3, Tomatis S.1, Pinnaduwage D.3, Nash M.4, Pignoli E.1, Roach M.4,
Gottschalk A.4, Valdagni V.R.2
National Cancer Institute, Division of Physics, Dept. of Radiation Oncology, Milan, Italy, 2National Cancer
Institute, Dept.of Radiation Oncology, Milan, Italy, 3UCSF, Division of Physics, Dept. of Radiation Oncology,
San Francisco, Ca, United States of America, 4UCSF, Dept. of Radiation Oncology, San Francisco, Ca,
United States of America
Introduction & Objectives: Developing treatment plans for prostate cancer patients undergoing
stereotactic body radiation therapy (SBRT) is often challenging due to the close proximity of critical
organs such as bladder and rectum.Currently, standardized dose constraints relating dose-volume
histogram’s parameters with threshold toxicity for hypo-fractionated high-dose regimen are not available
in the literature and dosimetric objectives might be relaxed or improved for patients with unfavourable
or favourable anatomy, respectively.Determining whether optimal radiation dose distribution has been
achieved for an SBRT prostate treatment is a subjective process that depends on physician’ and planner’s
experience.The objective of this study was to develop a simple evidence-based method for evaluating
achievable and patient-specific dose constraints for bladder and rectum to guide both the treatment
planning optimisation process and plan quality evaluation.
Material & Methods: In a recent paper1, a new method for a quantitative assessment of volumes
geometry in radiotherapy planning was suggested. To account for patient anatomy, this work suggests to
quantify the proximity of the organs at risk (OARs) to the target volume adopting the expansion-intersection
volume (EIV). This parameter represents the intersection volume between the OARs expanded by 5mm
and the target volume, and increases with increasing extension and proximity of these OARs to the
target. For each developed SBRT treatment plan, once the target coverage goal is achieved and the plan
quality is deemed acceptable by at least one experienced physician and physicist, the volumes of bladder
and rectum receiving 75% of the prescription dose (V75) as well as the EIV have to be collected.After a
sufficient number of cases are recruited (i.e. ≥20), data can be analysed.
Results: Analysis of collected data results in a linear correlation between EIV and V75 of bladder and
rectum, confirming that rectum and bladder V75 increase with increasing extension and proximity of these
OARs to the target. This correlation enables to easily develop a SBRT technique-specific linear algorithm to
define patient-specific dose objectives that should be achieved for future treatment plans.
Conclusions: We have developed a method to define patient-specific dose constraints for the optimization
of SBRT treatment plans. This technique-specific information can be used during the planning stage both
to orient the plan optimization process and to facilitate the evaluation of the plan quality and consistency
(1Tomatis Stefano et al. Geometry of volumes in radiotherapy planning. A new method for a quantitative
assessment. Tumori 97, 2011; 503-9). Thanks to ProADAMO Found. for supporting these study.
137
Unmoderated Posters
1
P097
Posttranslational modification of prostate-specific phosphodiesterase 11A4 in prostate
carcinoma
Schilling D.1, Hennenlotter J.1, Stenzl A.1, Gross-Langenhoff M.2
University of TГјbingen, Dept. of Urology, TГјbingen, Germany, 2University of TГјbingen, Institute of
Pharmacology, TГјbingen, Germany
1
Unmoderated Posters
Introduction & Objectives: Posttranslational modifications modulate the activity of most eukaryote
enzymes. In vitro assays gave evidence that cGMP binding to the regulatory GAF-domains of
phosphodiesterase 11A4 might activate the catalytic domain. N-terminal shortening of PDE11A4
substantially increases the affinity of cGMP for the GAF domain of the protein, resulting in a rise of catalytic
activity. The objective of this study was to assess posttranslational proteolytic modification of PDE11A4 in
the human prostate, as the protein is particularly abundant in this tissue. In a preliminary investigation we
aimed to determine proteolytic processing in benign and malignant prostatic tissues.
Material & Methods: Nine fresh frozen and histologically confirmed prostate carcinoma (PCa) samples
(median Gleason score 7 (6 - 8), median PSA 9.0 ng/ml (4.1 – 27.5), 4x pT2c, 4x pT3a, 1x pT3b) and 7
samples with benign prostatic tissue were included. Two specimens from renal parenchyma and 2 from
testicular parenchyma, as well as murine tissue samples from heart, muscle, kidney, bladder, uterus and
skeletal muscle served as a reference for proteolytic activity. Samples were homogenized and tested with
a recombinant human PDE11A4 construct including the N-terminal domain and its GAF-domains (amino
acids 1-568) as a substrate. Proteolytic activity in prostate homogenates was assayed by determination of
the O.D. at 420 nm using azocasein as a substrate.
Results: Homogenates from mouse heart, kidney, bladder, uterus or skeletal muscle did not hydrolyse
recombinant PDE11A4, respectively. However homogenates of human benign prostate, testis and renal
tissue, exhibited high proteolytic activity. Proteolytic processing in human prostate tissue homogenates
resulted in two distinct degradation fragments. The addition of various protease inhibitors indicated that
the process was mediated by cysteine-proteases. Homogenates of malignant prostatic tissue constantly
exhibited lower proteolytic activity. Serum-PSA and Gleason Score negatively correlated with the
proteolytic activity.
Conclusions: We show that PDE11A4 is a substrate for cysteine proteases in prostatic tissue. Proteolytic
cleavage of the enzyme is lower in PCa tissue samples. The decrease in proteolytic activity inversely
correlated with PSA and the Gleason Score. The present data indicate that PDE-dependent signalling
pathways might be altered on a posttranslational level in PCa.
138
P098
Analysis of association between single nucleotide genetic variant rs378854 and prostate
cancer risk in Serbian population
Kojic A.1, Brajuskovic G.1, Savic Pavicevic D.1, Nikolic Z.1, Vukotic V.2, Tomovic S.3, Vukovic I.4, Cerovic S.5,
Romac S.1
Faculty of Biology University of Belgrade, Dept. of Biochemistry and Molecular Biology, Belgrade, Serbia,
Clinical Centre Dragisa Misovic, Dept. of Urology, Belgrade, Serbia, 3Clinical Centre Zvezdara, Dept. of
Urology, Belgrade, Serbia, 4Clinical Centre of Serbia, Clinical of Urology, Belgrade, Serbia, 5Military Medical
Academy, Institute of Pathology, Belgrade, Serbia
1
Introduction & Objectives: Prostate cancer is the second most common cancer among men worldwide.
Despite its high incidence rate, the molecular basis of prostate cancer onset and progression still remain
poorly understood. Genome-wide association studies (GWAS) gave a great contribution to identification of
single nucleotide polymorphisms (SNP) which are associated with prostate cancer risk. Several GWAS identified 8q24 as a one of the most significant prostate cancer associated regions. The goal of this study is to
evaluate the association of SNP rs378854 in region 8q24 with prostate cancer risk in Serbian population.
Material & Methods: The study population included 261 individuals diagnosed with prostate cancer and
257 individuals diagnosed with benign prostatic hyperplasia (BPH) who provided peripheral blood samples
and 106 healthy individuals comprising the control group from whom the buccal swabs were obtained.
Informations about prostate-specific antigen serum level, Gleason score and clinical stage were available
for individuals diagnosed with prostate cancer. The genotypization of rs378854 was performed by
fragment analysis in automatic sequenator (3130 Genetic Analyzer, Applied Biosystems). The differences in
alelle and genotype frequencies between case and control subjects were performed using PLINK statistical
software.
Results: Data quality analysis yielded results showing deviations from Hardy-Weinberg equilibrium in study
groups of patients diagnoses with prostate cancer and BPH and also in control group. There was no significant association between the alleles and genotypes of the genetic variant rs378854 and prostate cancer
risk. Also, there was no statistical significance for alternative genetic models of association of rs378854
with prostate cancer risk. No statistically significant correlation was shown between the alleles and genotypes of the rs378854 and the values of standard prognostic parameters for prostate cancer. The rs378854
also showed no statistically significant differences in allele and genotype frequencies between risk groups
for prostate cancer progression.
Conclusions: The genetic variant rs378854 showed no association with prostate cancer risk in Serbian
population. Probable cause for the deviation of Hardy-Weinberg equilibrium in study groups is strong
selective pressure against allelic variants of rs378854. Future studies should provide definitive resolution
to possible association of rs378854 with prostate cancer risk in Serbian population.
139
Unmoderated Posters
2
P099
BPH and prostate cancer: One origin one mechanism two stages. A newly discovered route for
testosterone to reach the prostate directly from the testes
Gat Y.1, Goren M.2, Rosenbaum E.3
Weizmann Institute of Science, Depts. of Molecular Genetics and Sub Micron Research, Condensed Matter
Physics, Rehovot, Israel, 2Maynei Hayeshua Medical Center, Andrology-Inerventional Radiology, Bnei Brak,
Israel, 3Rabin Medical Center, Davidoff Research Center, Oncology Dept., Petach Tikva, Israel
Unmoderated Posters
1
Introduction & Objectives: The prostate, an androgen regulated exocrine gland is an integral part of
the male reproductive system. Free testosterone (FT) is the obligatory regulator of the prostate cell that
known to promote the evolution of BPH and prostate cancer (PCa). Researchers have been puzzled by the
paradoxical behavior of PCa and BPH in relation to serum Testosterone (T). Though PCa or BPH evolution
depend on testosterone, in over seven decades of research, no causal relation between serumT and
prostatic diseases В has been established and few enigmas still associate the disease. Here we report on
multidisciplinary study that result in the discovery of unrecognized route of flow of FT to reach the prostate
at extreme concentration, some 130 above physiologic, bypassing the systemic circulation, undetected in
the peripheral blood tests, directly to the prostate. This condition, derives from the wearing out of the one
way valves in the vertical internal spermatic veins (ISV) which its prevalence increases with age; the result
is elevated hydrostatic pressures in the testicular venous system that causes diversion of the venous flow
from the testes, carrying extreme concentration of FT, via the testicular and prostate drainage systems by
retrograde back-flow directly to the prostate.
Material & Methods: (i). 109 BPH patients and В (ii) 11 localized prostate cancer patients were treated.
The treatment (which can be done also by microsurgery) by sclerotherapy of the ISV, reduces the pathologic pressure to normal in the ISV which result in normal venous flow. Retrograde back-flow of FT via the
testicular-prostatic drainage systems directly from the testes to the prostate is stopped. Intra-prostatic FT
supply returns to normal via the prostate artery only.
Results: The treatment has resulted in significant decrease in prostate volume, and prostate symptoms
and disappearance of cancerous cells on repeat biopsies in 7 out of 11 patients with localized prostate
cancer. Early observations indicate that using ADT parallel to the treatment yields better results.
Conclusions: The findings may explain the pathophysiologic mechanism for the development of BPH and
prostate cancer and may resolve several enigmas associate these diseases.There is a time-window of
opportunity for effective treatment of localized PCa when prostate cancer cells are still dependent on high
concentration of testosterone for their survival.
140
P100
Streamlining the urology MDT meeting – Survey results from a national sample
Jalil R.1, Lamb B.1, Green J.S.A.2, Sevdalis N.1
Imperial College London, Dept. of Surgery and Cancer, London, United Kingdom, 2Whipps Cross Univeristy
Hospital, Dept. of Urology, London, United Kingdom
1
Material & Methods: A survey methodology was used. Participants included the attendees of two
national British Uro-oncology Group conferences in 2011 and 2012, members of the North Central London
Urology Audit Group, and, members of the North East London Cancer Network. An online survey using a
freely available survey engine (www.surveymonkey.com ) was constructed. The survey was aimed at the
three MDT core groups: Oncologists, Urologists and Clinical Nurse Specialists (CNS). Respondents were
asked to complete items related to their perception on the usefulness and logistics of the MDT meeting,
ways to better manage the caseload, and ways to optimize the discussion and decision-making.
Results: A total of 173 respondents completed the survey (Urologists=30, CNSs=54, Uro-oncologists=77
and others=12). The Oncologist spent more time at MDT meetings (median 3.0hrs/week, range 1-5hrs)
compared to Urologists (median 2.0hrs/week, range 2-4hrs) and CNSs (median 2.0hrs/week, range
0-5hrs). 68%(n=75) of respondents said that attending the MDT meeting improves efficiency in care of cancer patients in relation to: reaching clinical decisions/plans; planning appropriate investigations; discussing
plans with patients; specialty referrals; documentation/patient records. The majority of Urologists (66.5%)
and Oncologists (63.6%) agreed that some cases could be managed without going through MDT discussion
on explicit criteria, for example: Superficial/low grade bladder cancer or localised/low grade prostate
cancer. There was a consensus (81.3%) that MDT discussion could be prioritised by tumour type – however
splitting the MDT meeting into smaller meetings was not popular. Potential disadvantages of splitting the
MDT meeting were: time constrains; loss of MDT approach; inability of all members to attend all meetings;
increased administrative work.
Conclusions: This study reveals that Urology MDT members find the MDT meeting useful, and that
improvements to improve efficiency and effectiveness of MDT meetings are possible. Prioritising cases
appears a popular solution, but splitting into smaller MDT meetings is not. Further research is needed to
evaluate the suggestion of increasing efficiency by managing cases using previously agreed protocols.
141
Unmoderated Posters
Introduction & Objectives: Since 2004, the discussion of all patients with new cases of suspected or
diagnosed cancer by MDTs has been mandatory. Variation in case load between specialities has been
reported, and questions exist as to the utility of discussing all new cases, rather than those of recurrence.
Increasing research is currently being conducted to improve the quality of MDT working. The aim of this
study is to explore urology MDT members’ views on existing practices of MDT working, and to generate
potential interventions for improving the efficiency and productivity of the MDT meeting.
P101
The views of MDT coordinators on MDT meetings
Jalil R.1, Lamb B.1, Sevdalis N.1, Green J.S.A.2
Imperial College London, Dept. of Surgery and Cancer, London, United Kingdom, 2Whipps Cross University
Hospital, Dept. of Urology, London, United Kingdom
1
Unmoderated Posters
Introduction & Objectives: Cancer care worldwide is increasingly delivered in the context of
Multidisciplinary team MDT. MDT typically consists of surgeons, oncologists, radiologists, pathologists,
clinical nurse specialists and MDT coordinators. The role of the MDT Coordinator is relatively new, and as
such it is evolving. MDT coordinators play a key role in MDTs. We aimed in this study to explore the views
and needs of MDT Co-ordinators, with emphasis on their educational needs.
Material & Methods: Data were collected through an online survey. Respondents completed various
questions related to their views on the current practice, MDT chairing, opinions on how to improve MDT
meetings, and educational needs.
Results: 265 coordinators responded to the survey from all over the UK. “MDTs are chaired by Surgeons”,
80% of the respondents reported. 68% of respondents thought that MDT chairmanship could rotate; only
24% reported that it does in their own MDTs. Majority of the MDT coordinators reported having training on
data management and IT skills while more than 50% reported that further training is needed in areas of
Oncology, Anatomy and physiology, audit and research, peer review and leadership.
Conclusions: The role of the MDT coordinator is central to the care of cancer patients, both locally, and
also through the coordination and sharing of data on a wider level. Areas of training requirements remain
unmet. We emphasis on the need to strengthen their position by improving resources and training available
to MDT coordinators to improve team performance and consequently cancer care.
142
P103
Don’t forget the patient: Factors that impact on decision-making and decision implementation
in cancer MDT meetings
Jalil R.1, Ahmed M.1, Sevdalis N.1, Green J.S.A.2
Imperial College London, Dept. of Surgery and Cancer, London, United Kingdom, 2Whipps Cross University
Hospital, Dept. of Urology, London, United Kingdom
1
Material & Methods: A qualitative, interview-based approach was used to explore the key issues
surrounding MDT decision-making and implementation – in particular barriers and strategies for
improvement. Semi-structured interviews were carried out with surgeons, oncologists, pathologists,
radiologists and clinical specialist nurses (CNS) across both Urological and Gastro-intestinal (GI) tumours.
All interviews were audio-taped and transcribed verbatim and analysed using a standardised previously
validated approach. Emergent themes were identified by 2 clinical coders and disagreements resolved
through consensus.
Results: A total of 22 participants took part in the study (Urologists=5, Uro-oncologists=3, Urology
CNS=3, Histopathologists=1, Uro-radiologists=1, GI surgeons=3, GI CNSs=3 and GI Oncologists=3).
Barriers to reaching a management plan at the MDT included: inadequate clinical information; lack of
investigation results (histopathology and/or radiology); missing clinical notes and non-attendance of key
members. Barriers to implementation of MDT recommendations included: non-consideration of patients’
choices or comorbidities in the case discussion; disease progression at the time of implementation.
Proposed solutions to improving decision-making and its implementation included improving the
information available for the discussion through a standardised proforma; improving video-conferencing
and decreasing the MDT caseload for example by splitting the MDT meeting by tumour type or devising
explicit case criteria for MDT discussion.
Conclusions: There is an increasing drive to improve decision-making and implementation within cancer
MDTs. This study uncovers the main barriers that MDTs face in deciding on and implementing a management plan. Further research is needed to prospectively evaluate the efficacy and feasibility of interventions
to enhance decision-making and implementation and thus enhance cancer care.
143
Unmoderated Posters
Introduction & Objectives: In the UK it is mandatory for all cancer cases to be discussed at a
multidisciplinary team meeting (MDT) in order to obtain expert opinion and formulate a management plan.
Evidence suggests that MDTs do not work optimally in reaching a decision in all cases. Furthermore 1-20%
of MDT decisions do not get implemented. This study investigated factors influencing decision-making and
decision implementation in cancer MDTs.
P104
Expressions of biomarkers to predict overall and cancer-specific survival of prostate cancer
Peng Z.1, Skoog L.1, Hellborg H.2, Jonstam G.3, Wingmo I.4, Hjälm-Eriksson M.3, Harmenberg U.3,
Cedermark G.C.3, Г„hrlund-Richter L.5, Pramana S.6, Pawitan Y.6, NistГ©r M.1, Nilsson S.1, Li C.1
1
Karolinska Institutet, Dept. of Oncology-Pathology, Stockholm, Sweden, 2Karolinska University Hospital,
Regional Oncologic Center, Stockholm, Sweden, 3Karolinska University Hospital, Dept of. Clinical Oncology,
Stockholm, Sweden, 4Karolinska University Hospital, Dept. of Clinical Pathology/Cytology, Stockholm,
Sweden, 5Karolinska Institutet, Dept. of Women and Children's Health, Stockholm, Sweden, 6Karolinska
Institutet, Dept. of Medical Epidemiology and Biostatistics, Stockholm, Sweden
Unmoderated Posters
Introduction & Objectives: This study is aiming at identifying biomarkers to accurately predict overall
and cancer-specific survival in prostate cancer patients.
Material & Methods: In order to explore the importance of embryonic stem cell (ESC) gene signature, we
identified 641 embryonic stem cell gene predictors (ESCGPs). Selected ESCGPs and control genes were
analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis
from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients,
97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone
therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate
Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis.
Results: A published dataset was used for external validation. An expression signature of F3, VGLL3 and
IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes.
The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference
corresponded to HRs of 5.86 (95% CI 2.91-11.78, P<0.001) for the high-risk and 3.45 (95% CI 1.79-6.66,
P<0.001) for the intermediate-risk compared to the low-risk subtype. The obvious overall and cancerspecific survival difference between the three subtypes was still maintained within the patients primarily
treated by hormone therapy. The overall survival rate at 8 years of three subtypes was 0%, 16% and
55.6%, respectively. This obvious survival difference was independent of age, PSA level, tumor grade and
clinical stage.
Conclusions: These results suggest that this expression signature could be used to improve the accuracy
of the currently available clinical tools for predicting overall and cancer-specific survival and selecting
patients with potential survival benefit from hormone treatment.
144
P106
Frequency of brain metastases (BM) from prostate cancer (PC): An 18-year single institution
experience
Caffo O.1, Veccia A.1, Fellin G.2, Mussari S.2, Russo L.M.1, Galligioni E.1
Santa Chiara Hospital, Dept. of Medical Oncology, Trento, Italy, 2Santa Chiara Hospital, Dept. of
Radiotherapy, Trento, Italy
1
Material & Methods: We reviewed the clinical records of all pts with BM referred at Santa Chiara Hospital
ORDs from 1994 to 2011: since DOC was introduced into our clinical practice in 2003, we separately
evaluated two periods (P1: 1994-2002; P2: 2003-2011). We limited our search to male pts to avoid the bias
due to the incidence of BM from breast cancer. For each pt we assess the primary tumor diagnosis and in
the case of PC diagnosis we recorded all relevant issues of the clinical history.
Results: In the study period 490 males with BM were referred to our ORDs (P1 = 241 pts; P2 = 249). The
most frequent recognized primary tumor was lung cancer, with a similar percentage of BM for P1 and P2
(58.9 vs 60.6%). Concerning PC we collected a series of 9 pts with BM: 2 pts in P1 and 7 in P2 (0.8% and
2.8%, respectively). The median age at the diagnosis of PC was 64 yrs (range 65-78). All but 2 pts had a
CRPC: among them, 6 pts developed BM during or after a DOC-based chemotherapy and 1 before first line
DOC start. The median interval from the PC diagnosis and the achievement of CRPC was 25 mos (range
5-84) while the appearance of BM was documented after 0-111 mos (median 36) from diagnosis. The
median survival after BM was 8 wks (range 1-54).
Conclusions: Our data appear to confirm that: 1) the BM from PC pts are more frequent than in the past;
2) this finding could be related to a survival improvement due to DOC introduction in the clinical practice;
3) a special attention should be reserved to the appearance of neurological symptoms in a long-term CRPC
survivor due to a possible relation with BM.
145
Unmoderated Posters
Introduction & Objectives: We have recently reported in a multicenter survey a 3.5% incidence of BM in
castration resistant PC (CRPC) patients (pts) (J Neurooncol 2012). Due to the lack of incidence data before
docetaxel (DOC) introduction in the participating Hospitals, we compared this value to historical series
published before DOC era and it seemed to be higher (3.5 vs ..%). In the present survey, we assessed all
pts who were referred to our Oncologic & Radiotherapy Departments (ORDs) in the last two decades in the
aim to detect differences over the time in BM due to PC.
P107
Dosimetric evaluation of the feasibility of an intraprostatic boost according to gross-tumorvolumes (GTVs) location for prostate cancer patients treated with combined external beam
radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT)
Helou J.1, Verstraet R.2, Blanchard P.1, Rodriguez A.2, Lefkopoulos D.2, Bourhis J.1, Calmel L.2, Azoury F.1,
Bossi A.1
1
Institut Gustave Roussy, Dept. of Radiation Oncology, Villejuif, France, 2Institut Gustave Roussy, Dept. of
Medical Physics, Villejuif, France
Unmoderated Posters
Introduction & Objectives: HDR-BT allows for dose escalation to the whole prostatic gland volume
and for a selective intra-prostatic GTV boost. Short and long term urethral and rectal toxicity may limit
intra-prostatic dose escalation. Our study aims to identify the dosimetric feasibility and limitations of an
intra-prostatic boost to different GTVs locations according to 4 dose levels.
Material & Methods: The study was conducted on 18 patients treated on an institutional protocol of combined HDR-BT single fraction of 9.5 Gy (= Prescribed dose, PD) followed by EBRT delivered with Intensity
modulated technique (IMRT). The GTV locations studied for the intra-prostatic boost were; postero-lateral,
total posterior, antero-lateral, total anterior and 3 volumes in the apical zone characterized by different
heights in the apex-base direction: 15, 20 and 25 mm. All patients had a standard optimization with the 90
% of the CTV receiving 100 to 105 % of the PD. Four boost-dose levels were studied: 100%, 120%, 135 %
and 150% of the PD. The urethral and rectal D0.1 and D0.5 cc were reported for every dose level.
Results: An intraprostatic dose escalation on the postero-lateral GTV had no significant impact on the
urethral D0.1cc and D0.5cc, while a significant increase in the rectal D0.1cc (74, 77, 80 and 84% for
every dose level respectively) and D0.5cc (68, 70, 72 and 75 %) was noted (p< 0.05). Similarly, a boost
on the total posterior GTV had a significant impact on the rectal D0.1cc (74, 77, 78 and 81%) and D0.5cc
(67, 70, 71 and 73 %) (p< 0.05), while the urethral D0.1cc increased significantly only for a boost of
150% (p=0.013). An antero-lateral and total anterior boost significantly increased the urethral D0.1cc
for a dose ≥135% (p= 0.007 and 0.01 respectively) while significantly decreasing the rectal doses. No
significant impact of an apical dose escalation was seen on the urethra whereas the rectal doses increased
significantly for a boost ≥135% (p<0.05). No major increase on rectal and urethral doses was observed
with the 120 % boost level except for the posterior GTV (D0.1cc=77%). However, this increase is still within
acceptable limits.
Conclusions: Delivering an intra-prostatic boost dose of 120 % of the PD with HDR-BT is feasible and safe
regardless of the GTV location. Further increases of the intra-prostatic boost dose may be possible only by
carefully evaluating the spatial distribution of the GTV as well as the rectal and urethral doses.
146
P108
Helical tomotherapy in prostate cancer: Minimizing toxicity
Acebedo C.1, LГіpez Guerra J.L.1, Rivin Del Campo E.2, Matute R.1, Isa N.1, Puebla F.1, Russo M.3,
Sanchez-Reyes A.4, BeltrГЎn C.1, JaГ©n J.1, Marsiglia H.5
Introduction & Objectives: Radiation-induced toxicity is an important adverse event that affects most
patients receiving radiation therapy (RT) for prostate cancer (PC), especially for those who underwent
prior treatment such as surgery. Intensity modulated radiation therapy has been shown to decrease acute
toxicity. We present the clinical results of intensity-modulated radiation therapy with helical tomotherapy
(HT) for clinically localized and recurrent PC, as well as post-prostatectomy adjuvant treatment.
Material & Methods: From May 2006 to January 2011, 70 cT1-T3 cN0 cM0 PC patients were treated with
HT (primary diagnosis, n=48; post-prostatectomy biochemical recurrence, n=15; post-brachytherapy biochemical recurrence, n=2; and post-prostatectomy adjuvance, n=5). The dose prescribed to the prostate
ranged between 72-78Gy, except for one case (post-brachytherapy recurrence, 66Gy) with conventional
fractionation (2Gy/fraction). The seminal vesicles received between 50-56Gy, the surgical bed 66-74Gy,
and the pelvic lymph nodes 46-50.4Gy (n=20), respectively when applicable, with conventional fractionation. Minimum follow-up was 3 months. Demographic, tumor and treatment characteristics were recorded
and analyzed. The follow-up was calculated from the HT start date to the last contact date. For patients
with a primary diagnosis or those receiving adjuvant HT, survival time was measured from the diagnosis
date to the last contact date for alive patients or the date of death if the patient had died. For patients
receiving HT for biochemical recurrence, survival time was measured from the recurrence diagnosis date
to the last contact date for alive patients or the date of death for deceased patients. Genitourinary (GU)
and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group (RTOG) scoring
system.
Results: The median age was 68 years (range 51-87 years). The median follow-up was 37 months (range
3-74 months). The mean initial Gleason score was 6 В±1 and the mean initial PSA was 17.11ng/ml В±35. The
mean total dose was 75.48Gy В±2.88 for prostate, 54.04GyВ±1.13 for seminal vesicles, 67.8GyВ±3.7 for the
surgical bed, and 46.32В±1.4 for pelvic lymph nodes. The mean vesical and rectal volumes were 149ccВ±90
and 79.05cc В±28, respectively. For patients with a primary diagnosis or those receiving adjuvant HT,
median overall survival was 45 months (range, 8-82 months). For patients receiving HT for biochemical
recurrence, overall survival was 24 months (range, 3-73 months). Overall, only 3 patients died, and none
of them due to a cancer-related cause. Local recurrence was seen in 1 patient which had been treated for
a biochemical recurrence after initial prostatectomy. Regional recurrence and bone disease only occurred in one patient with primary intermediate risk PC. The rates of acute grade 2 gastrointestinal (GI) and
genitourinary (GU) toxicities were 13% and 10 %, respectively. Only one patient experienced acute grade 3
GU toxicity. The rates of late grade 2 GI toxicities were 1.5%, and those of late grade 2 GU toxicities were
1.2 %. No patients experienced late Grade ≥3 toxicity.
Conclusions: This preliminary report confirms the feasibility of HT. Tomotherapy is associated with a very
low risk of toxicity and a low recurrence rate. Acute and late gastrointestinal and genitourinary toxicities
were tolerable without any grade > 3 side effects. Further research is necessary to assess definitive late
toxicity and tumor control outcome.
147
Unmoderated Posters
1
Instituto MadrileГ±o De OncologГ­a/Grupo IMO, Dept. of Radiation Oncology, Madrid, Spain, 2Hospital
General De Elche. ERESA, Dept. of Radiation Oncology, Elche, Spain, 3Radiomedicine Institute IRAM, Dept.
of Radiation Oncology, Santiago, Chile, 4Instituto MadrileГ±o De OncologГ­a/Grupo IMO, Dept. of Radiation
Physics, Madrid, Spain, 5Institut De CancГ©rologie Gustave Roussy, Dept. of Radiation Oncology, Villejuif,
Paris, France
P109
Efficacy and safety of a 3-monthly depot formulation of degarelix compared with goserelin in
prostate cancer
Tombal B.1, Tammela T.L.J.2, Wolff J.M.3, Payne H.4, Crawford E.D.5, Shore N.6, Gittelman M.C.7, Olesen T.K.8,
Persson B.9, Klotz L.10
Unmoderated Posters
1
Cliniques Universitaires Saint Luc/UniversitГ© Catholique De Louvain, Service D'Urologie, Brussels,
Belgium, 2Tampere University Hospital, Division of Urology, Tampere, Finland, 3Viersen General Hospital,
Dept. of Urology, Viersen, Germany, 4University College Hospital, Dept. of Clinical Oncology, London,
United Kingdom, 5University of Colorado Cancer Center, Dept. of Urologic Oncology, Aurora, United
States of America, 6Carolina Urologic Research Center and Atlantic Urology Clinics, Dept. of Urology,
Myrtle Beach, United States of America, 7South Florida Medical Research, Dept. of Urology, Aventura,
United States of America, 8Ferring Pharmaceuticals, Clinical R&D, Copenhagen, Denmark, 9Ferring
Pharmaceuticals, Medical Sciences, St-Prex, Switzerland, 10University of Toronto, Dept. of Surgery,
Toronto, Canada
Introduction & Objectives: Once-monthly degarelix 240/80 mg significantly improved prostate-specific
antigen (PSA) progression-free survival vs. leuprolide in prostate cancer (PCa). This 1-year, open-label,
randomised study (CS35, NCT00946920) evaluated a 3-monthly degarelix formulation.
Material & Methods: Patients received degarelix (240 mg, then 480 mg every 3 months) or goserelin
(3.6 mg, then 10.8 mg every 3 months) В± bicalutamide. Co-primary endpoints were cumulative probability
of testosterone ≤0.5 ng/mL: from Days 3–364 for degarelix vs. goserelin and from Days 28–364 with
degarelix.
Results: Overall, 848 patients received treatment (degarelix, n=565; goserelin, n=283). The first endpoint
(castrate from Days 3–364 vs. goserelin) was met; indeed, degarelix was statistically superior to goserelin
(cumulative probability, 85% [81.6–87.8%] and 5.3% [3.1%–8.4%], respectively). The second endpoint
(castrate from Days 28–364) was not met as the lower bound of the 95% CI was below the predefined 90%
threshold (cumulative probability, 90% [95% CI, 87.0–92.3%]). This reflects testosterone escape in some
patients as a result of insufficient trough plasma degarelix levels at the end of the 3-month dosing period.
Compared with goserelin, degarelix was not associated with initial testosterone surge and microsurges;
it demonstrated a significantly faster PSA suppression and lower urinary tract symptom relief (in locally
advanced disease) as well as lower incidence of arthralgia; and a significantly lower risk of disease progression (in those with high baseline PSA; i.e. >50 ng/ml) (Table 1). Overall incidences of adverse events (AEs)
were similar for degarelix vs. goserelin (75% vs. 71%). Injection site reactions were more common with
degarelix (39% vs. 2%), while renal/urinary (9% vs. 17%) and musculoskeletal AEs (14% vs. 20%) were more
common with goserelin. Table 1. Degarelix vs. goserelin В± bicalutamide in PCa.
148
Degarelix (n=565)
Goserelin В± bicalutamide (n=283)
Testosterone
В В Median level, Day 3 (ng/mL)
0.27
6.9
PSA
В В Median % reduction, Day 28
84†66
Probability of PSA failure, %
Overall population
Baseline PSA >50 ng/mL
13.5
34.9
13.5
45.0
Disease progression a
В В Probability of disease progression, %
Overall population
Baseline PSA >50 ng/mL
21.0
42.2*
22.7
59.2
Symptom control
В В Change in IPSS, Day 28
Overall population
Locally advanced PCa
-0.99
-1.44*
-0.20
0.22
В В -3.76
-11.2*
-3.16
-5.94
Arthralgia b
Change at Day 28
Overall population
Metastatic disease
Table 1. Degarelix vs. goserelin В± bicalutamide in PCa
*p<0.05; †p<0.0001 vs. goserelin a PSA failure, death or additional PCa therapy; bvisual analogue
scaleIPSS, International Prostate Symptom Score
Conclusions: Treatment with 3-monthly degarelix was associated with a number of clinical benefits vs.
goserelin in patients with PCa. These benefits are consistent with the results obtained in previous studies
with once-monthly degarelix and confirm its role as a first-line androgen-deprivation therapy in PCa.
149
Unmoderated Posters
В P110
Efficacy and tolerability of 3- and 6- month depot formulations of leuprorelin acetate for
advanced prostate cancer in daily clinical practice: Pooled data from 2 non-interventional
studies
Ohlmann C.H.1, Gross-Langenhoff M.2, Tunn U.W.3
Saarland University, Dept. of Urology, Homburg / Saar, Germany, 2Astellas Pharma GmbH, Medical Department, Munich, Germany, 3Urological Clinic Facharztzentrum Klinikum Offenbach, Urological Department,
Offenbach / Main, Germany
Unmoderated Posters
1
Introduction & Objectives: Androgen-deprivation therapy is the current standard therapy for advanced
prostate cancer (PCa). This therapy often consists of injections of luteinising-hormone-releasing-hormone
(LHRH) agonists. The LHRH agonist leuprorelin acetate (LA) is available in several formulations, including
1-, 3- and 6- month biodegradable polymer matrix depot formulations (EligardВ®), which have been shown
to reduce testosterone and PSA levels in several clinical trials (Crawford ED et al. J Urol 2006;175:533-6/
Perez-Marrero R et al. Clin Ther 2002;24:1902-14/Chu FM et al. J Urol 2002;168:1199-203). The current
study aimed at monitoring efficacy and tolerability of these formulations in PCa patients seen in daily
clinical practice.
Material & Methods: Two prospective, open-label, non-interventional studies were conducted in Germany.
1,906 advanced PCa patients starting treatment with either the 3-month (22.5 mg) or the 6-month (45 mg)
LA depot formulation (Eligard В®) were followed during 12 months by 662 office-based urologists. Primary
efficacy parameters total serum testosterone and PSA were measured at baseline and every 3 (for 22.5
mg dose) or 6 (for 45 mg dose) months until 12 months after treatment initiation. Physicians were also
asked to rate ease of use and local tolerability of the treatment.
Results: Median testosterone levels were reduced by 90% from 88.8 ng/dl to 8.9 ng/dl 12 months after
treatment start. Testosterone reduction below the castration level was achieved both in treatment-naГЇve
patients and in patients pretreated with LHRH agonists. Median serum PSA levels were reduced by 96%
from 12.2 ng/ml to 0.5 ng/ml 12 months after treatment start. About 2/3rd of physicians found handling
of the prefilled syringe (very) convenient, while >90% rated local tolerability as good or excellent. Adverse
events (AEs) occurred in 8.8% of patients, with injection site pain and hot flushes being the most common
ones.
Conclusions: These data confirm that the 3- and 6-month LA depot formulations reduce testosterone
and PSA levels to a similar extent in daily clinical practice as in clinical trials, both in treatment-naГЇve and
in pretreated patients. This study also confirms the good tolerability of the 3- and 6-month LA depot
formulations. The majority of physicians found handling of the prefilled syringe in routine clinical practice
(very) convenient.
150
P111
Early toxicity assessment of pelvic Volumetric Modulated Arc Therapy (VMAT) with
hypofractionated simultaneous integrated boost to prostate for high-risk prostate cancer
Ferrer F.1, Boladeras A.1, De Blas R.2, Puxeu J.2, Quispe K.1, Garcia I.1, Del Carpio A.1, Bejar S.1, Zardoya E.2,
Guedea F.2
Institut CatalГ D'Oncologia, Dept. of Radiation Oncology, L' Hospitalet-Barcelona, Spain, 2Institut CatalГ D'Oncologia, Dept. of Medical Physics, L' Hospitalet-Barcelona, Spain
1
Material & Methods: A retrospective toxicity analysis was performed in 10 consecutive patients treated
definitively with pelvic SIB-VMAT, all of whom also received androgen suppression. The VMAT plans were
designed to deliver 67,5 Gy in 27 fractions (2.5 Gy/fraction) to the prostate, 59,4 Gy (2,2Gy/fraction) while
simultaneously delivering 48.6 Gy in 27 fractions(1.8 Gy/fraction) to the pelvic lymph nodes. Prostate dose
was equivalent to 78 Gy at 2 Gy per fraction considering an alpha/beta of 1,5 Gy. VMAT was delivered by
two arcs. Dose constraints for bladder and rectal volumes receiving 70, 60 an 40 Gy were less than 25%,
40 and 60% respectively. The National Cancer Institute Common Terminology Criteria for Adverse Events,
version 3.0, was used to score toxicity.
Results: One patient showed a biochemical relapse during the follow-up period. The most common acute
Grade 2 events were cystitis (80%) and urinary frequency/urgency (90%). Rectal acute toxitiy grade 2 with
mucosal discharge was present in 70% of patients. At a median follow-up of 6 months, no late toxicity
exceeding Grade 2 was seen. Mean bowel volume for V30, V40, V50 and V60Gy were 0,36; 4,06; 32,48;
54,39 cc respectively. Grade 2 acute or late bowel toxicity was not associated with bowel volume receiving
V30, V40,V50, V60Gy. Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric
parameters examined.
Conclusions: Pelvic VMAT with SIB to the prostate was well tolerated in this series, with low rates of
Grade 2 or greater acute and late toxicity. SIB-VMAT combines pelvic radiotherapy and hypofractionation
to the primary site and offers an accelerated approach to treating high-risk disease. Additional follow-up
is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined
with androgen suppression.
151
Unmoderated Posters
Introduction & Objectives: Pelvis irradiation in high-risk prostate cancer is a subject of debate. Bowel
radiation toxicity limits dose escalations for prostate cancer. The purpose was to evaluate the toxicity of
pelvic VMAT with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with
high-risk or very high risk prostate cancer.
P112
Pre-treatment (pre-tx) neutrophil to lymphocyte ratio (NLR) in metastatic castration resistant
prostate cancer (mCRPC) patients (pts) treated with ketoconazole (keto): Association with
outcome and predictive model
Keizman D.1, Ish-Shalom M.1, Maimon N.1, Gottfried M.1, Peer A.2, Neumann A.2, Rosenbaum E.3, Kovel S.4,
Pili R.5, Sinibaldi V.6, Hammers H.6, Carducci M.6, Eisenberger M.6, Sella A.4
Unmoderated Posters
1
Meir Medical Center, Institute of Oncology, Kfar Saba, Israel, 2Rambam Medical Center, Department of
Oncology, Haifa, Israel, 3Rabin Medical Center, Department of Oncology, Petah Tikvah, Israel, 4Asaf Harofe
Medical Center, Department of Oncology, Zerifin, Israel, 5Roswell Park, Cancer Institute, Buffalo, United
States of America, 6Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center, Baltimore, United
States of America
Introduction & Objectives: The CYP17 inhibitor keto is active in mCRPC. The NLR, an index of systemic
inflammation, is associated with prognosis in several types of cancer. We assessed the association
between pre-tx NLR and outcome of mCRPC pts treated with keto.
Material & Methods: We performed an international multicenter retrospective study of pts with mCRPC,
who were treated with keto. We analyzed the pre-tx NLR and previously described factors associated with
keto tx outcome as prior response to hormonal tx, pre-tx PSADT, and extent of metastatic disease (limited
vs extensive). Progression free survival (PFS) was determined by the Kaplan-Meier method. Multivariate
analyses using Cox regression model were performed to determine their independent effect, and to form a
predictive model. A survival tree analysis was used to find the best NLR cut-off value.
Results: From 1999-2011, 156 mCRPR pts (median age 69) were treated with keto. 78/156 (50%) had ≥
50% PSA decline. Overall median PFS was 8 months (mos) (range 1-144). Excluded from the analysis were
23 pts without available data on pre-tx NLR or with recent (≤1 mos) health event or tx (surgery, steroids,
radiation) associated with a change of blood counts. 133 pts were included in the analysis. 62 (47%) had
an elevated pre-tx NLR >3. Risk factors associated with PFS (table) were pre-tx NLR >3, prior response to
GnRH-a <24 mos and to antiandrogen (AA) <6 mos, and pre-tx PSADT <3 mos. The number of risk factors
was used to categorize patients into three risk groups (table): favorable (0-1 factors), intermediate (2
factors), and poor (3-4 factors).
Conclusions: In mCRPC pts treated with keto, pre-tx NLR, prior response to hormonal tx, and pre-tx
PSADT are associated with PFS, and may be used to categorize pts into risk groups. Table
Factor
PFS (mos) (HR, p value)
NLR ≤ 3 vs >3
14 vs 3, (0.353, <0.0001)
Response to prior GnRH-a ≥ 24 vs < 24 mos
12 vs 5, (0.513, 0.035)
Response to prior AA ≥6 vs <6 mos
18 vs 3, (0.445, 0.003)
Pre-tx PSADT ≥3 vs <3ms
14 vs 4, (0.449, 0.007)
Risk groups: favorable (n=67) vs intermediate (n=27) vs poor (n=62)
14 vs 7 (0.35, <0.0001) vs 3 (0.64, <0.0001)
152
P114
Safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase
inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer
(mCRPC): Phase 2 results from a phase 1/2 study
1
Yale University Cancer Center, Dept. of Oncology, New Haven, United States of America, 2Associates In
Oncology and Hematology, Dept. of Oncology, Chattanooga, United States of America, 3Alaska Clinical Research Center, Dept. of Oncology, Anchorage, United States of America, 4Karmanos Cancer Institute, Dept.
of Oncology, Detroit, United States of America, 5Thomas Jefferson University, Dept. of Medical Oncology,
Philadelphia, United States of America, 6Tisch Cancer Institute, Mount Sinai School of Medicine, Dept. of
Oncology, New York, United States of America, 7University of Southern California, Keck School of Medicine,
Dept. of Oncology, Beverly Hills, United States of America, 8Winship Cancer Institute, Emory University,
Dept. of Hematology, Atlanta, United States of America, 9Millennium Pharmaceuticals, Inc., Dept. of Oncology Clinical Research, Cambridge, United States of America, 10Takeda Global Research & Development
Centre (Europe) Ltd., Clinical Research, London, United Kingdom, 11University of Wisconsin Carbone Cancer
Center, Dept. of Oncology, Madison, United States of America
Introduction & Objectives: The investigational agent orteronel is a selective oral inhibitor of 17,20-lyase
that blocks androgen production. DP is currently standard chemotherapy in mCRPC and this phase 1/2
study examined orteronel + DP in men with mCRPC. The primary objective of the phase 2 portion is tolerability of orteronel 400 mg BID + DP in castrate men with mCRPC (testosterone <50 ng/dL). Secondary
objectives include PSA response rates at 3 months, best PSA response at any time, time to progression of
PSA В± radiographic disease, PK, and tumor response.
Material & Methods: Patients with confirmed progressive mCRPC and PSA ≥5 ng/mL received orteronel
400 mg BID + D (75 mg/m2 every 3 wks) + P (5 mg BID). No prior chemotherapy or ketoconazole /
abiraterone were allowed. Response was assessed by RECIST 1.1. In phase 2, all cycles were 21 d.
Results: 24 men were treated in phase 2: median age was 66 yrs (range 53–87), ECOG PS 0/1
(88%/13%). Median drug exposure for both orteronel and docetaxel was 4 cycles (1–10). At baseline,
median PSA was 47 ng/mL (4.5–813) and median testosterone was 7.2 ng/dL (3.2–13.8). Drug-related
adverse events (AEs) were reported in 22 men (92%), 19 of these were ≥Gr3 and those ≥10% were WBC
decreased (29%); neutropenia (25%); decreased neutrophil count (25%); fatigue, and febrile neutropenia
(each 13%). Drug-related serious AEs were reported in 8 men (33%); febrile neutropenia was the most
common at 13%. Discontinuations due to AEs occurred in 3 men (ALT increase, arthralgia, pneumonitis).
At the time of data cutoff, there were no on-study deaths and 15 men remained on study treatment. In
the PSA-evaluable population, PSA30, PSA50, and PSA90 rates at 3 months were 59%, 50%, and 18%,
respectively. Best PSA decrease at any time on study was a median decline of 76% (n=22; -99% to +144%).
Best objective response occurred in 50% of evaluable pts (n=10; 80% CI: 27,73; partial response was
observed in 5 of 10 evaluable men). Median time to PSA progression was 6.1 months (95% CI: 4.6, not
reached) and median time to radiologic progression was not yet reached. The Cmax of DP + orteronel was
similar to that of DP alone.
Conclusions: Treatment with orteronel 400 mg BID + DP appears tolerable and shows androgen-lowering
activity and strong tumor response in men with mCRPC. Plasma levels of D administered with orteronel + P
were similar to published data for DP alone.
153
Unmoderated Posters
Petrylak D.1, Gandhi J.2, Clark W.R.3, Heath E.I.4, Lin J.5, Oh W.K.6, Agus D.B.7, Carthon B.8, Moran S.9,
Mortimer P.10, Liu G.11
P115
A phase 2 multicenter study of the investigational single agent orteronel (ortl, TAK-700) in
nonmetastatic castration-resistant prostate cancer (nmCRPC) and rising prostate-specific
antigen (PSA)
Unmoderated Posters
Hussain M.1, Corn P.G.2, Michaelson D.3, Hammers H.J.4, Alumkal J.J.5, Ryan C.J.6, Bruce J.Y.7, Moran S.8,
Lee S.Y.8, Mortimer P.9, George D.J.10
1
University of Michigan Comprehensive Cancer Center, Dept. of Internal Medicine and Urology, Ann Arbor,
United States of America, 2MD Anderson Cancer Center, Dept. of Oncology, Houston, United States of America,
3
Massachusetts General Hospital Cancer Center, Dept. of Oncology, Boston, United States of America,
4
Sidney Kimmel Comprehensive Cancer Center, Dept. of Oncology, Baltimore, United States of America,
5
Oregon Health & Science University, Knight Cancer Institute, Dept. of Oncology, Portland, United States of
America, 6UCSF Helen Diller Family Comprehensive Cancer Center, Dept. of Oncology, San Francisco, United
States of America, 7University of Wisconsin Carbone Cancer Center, Dept. of Oncology, Madison, United States of America, 8Millennium Pharmaceuticals, Inc., Oncology Clinical Research, Cambridge, United States of
America, 9Takeda Global Research & Development Centre (Europe) Ltd., Oncology Research, London, United
Kingdom, 10Duke University Medical Center, Dept. of Oncology, Durham, United States of America
Introduction & Objectives: Ortl is a selective, investigational, non-steroidal, oral inhibitor of 17,20-lyase
with the potential for steroid-free dosing due to its lower inhibition of 17О±-hydroxylase. We evaluated ortl in
men with nmCRPC and rising PSA.
Material & Methods: Eligible men with nmCRPC, PSA ≥2 ng/mL, and doubling time (dt) ≤8 months ([mo];
if dt >8 mo, PSA had to be ≥8 ng/mL), castrate range testosterone (T) <50 ng/dL, and no prior ketoconazole, chemotherapy, or corticosteroids, received ortl at 300 mg BID in 28 d cycles until PSA progression,
metastases, or unacceptable toxicity. CT/MRI evaluations were done at screening, at cycles 4, 7, 10, 13,
and every 4th cycle thereafter. The primary endpoint was the percentage of men achieving PSA ≤0.2 ng/
mL at 3 mo. Secondary endpoints included safety, PSA response at 3 and 6 mo, time to metastases,
changes in endocrine markers and circulating tumor cells (CTCs). 38 patients provided 90% power for
1-sided significance level of 0.1 (H0 5% vs HA 20%) for the percentage of patients achieving a PSA of ≤0.2
ng/mL after 3 mo of ortl treatment.
Results: 39 men with median age 71 y (range 53–81), ECOG PS ≤1, median PSA 12.1 ng/mL (2.6–67.8),
T 7.9 ng/dL (1.4–17.3), and ACTH 19 ng/L (n=33; 0–47) were enrolled. At data cutoff, men had received a
median of 7 treatment cycles (1–21); 22 (56%) were on treatment >6 mo. 20 men reported adverse events
(AEs) ≥Gr3 irrespective of causality; those in ≥5% of men were hypertension (15%), dyspnea (8%), fatigue,
hypokalemia, pneumonitis (5% each). AEs led to discontinuing ortl in 8; 2 for adrenal insufficiency, only 1
had laboratory values consistent with a hypoadrenal state and received corticosteroid replacement. Serious
AEs occurred in 10 men (26%); pneumonitis (n=3 ≤Gr 3) was the most common. 3 men had Gr 4 AEs: 1 ea
with aortic valve disease, pulmonary embolism, and transitional cell carcinoma. 6 men achieved PSA ≤0.2
ng/mL (16%) at 3 mo; median PSA declined by 83% (n=34), and PSA50 and PSA90 rates (PSA declines of
≤50% and ≤90%, respectively) were achieved in 76% and 32%, respectively. Best PSA response: 12 (32%)
achieved PSA ≤0.2 ng/mL; 22 (58%) and 32 (84%) achieved PSA90 and PSA50, respectively. Median time
to PSA progression was 14.8 mo. Kaplan-Meier (KM) estimates of freedom from PSA progression were
97%, 91%, and 60% at 3, 6, and 12 mo, respectively. KM for freedom from metastasis was 97% at 6 and
12 mo (n=23, n=14, respectively). At 3 mo, median T declined 89% to 0.78 ng/dL (n=31), DHEA declined
85% to 197 nmol/L (n=34), cortisol declined 21% to 260 nmol/L (n=34), still within the normal range of
138–690 n/mol/L, and ACTH increased 171% to 43 ng/L (n=33); results were similar at 6 mo.
Conclusions: Ortl produces marked and durable declines in T and PSA without steroids, has manageable
toxicities, and is feasible in men with nmCRPC.
154
P116
Radical prostatectomy in clinically metastatic prostate cancer patients
Karazanashvili G.
SC "Modern Medical Technologies", Dept. of Urology, Tbilisi, Georgia
Material & Methods: 90 radical prostatectomies have been performed in our clinic from June 2010 to
June 2011. PC was clinically metastatic in 14 (of 90) patients. PSA varied from 16 to 132ng/ml (mean
57ng/ml). MRI detected lymph node hyperplasia (>1sm) in all patients. Bone scan detected few sites of
bone metastasis in 2 patients. Radical prostatectomy was performed in 13 (of 14) patients and radical
cystoprostatectomy – in 1 (of 14). Extended lymphadenectomy along internal and external ileac vessels
was applied in all cases. Nerve sparing procedure was possible to conduct in 8 (of14 cases).
Results: Intraoperative blood loss, postoperative hospital stay, and continence rates at 3 month were
similar in clinically metastatic (14 cases) and nonmetastatic (76 cases) patients. Pathologically lymph node
positive disease was detected in 12 (of 14) cases. In 2 (of 14) patients with PSA level 27 and 100ng/ml
no metastatic disease was detected on pathological examination. During 6 month after RP biochemical
recurrence occurred only in 6 (of 12) men, of which 2 were with bone metastasis preoperatively. In all this
cases PSA doubling time was < 6 month. Antiandrogens were effective to reduce PSA levels bellow 1ng/
ml in these men. After 1 year in 2 of these 6 patients medical or surgical castration was applied effectively
because of farther PSA progression (both of these men had bone metastasis preoperatively), while in the
remaining 4 (of 6) men antiandrogens were enough to control PSA levels.
Conclusions: RP is feasible in selected men with clinically metastatic PC. It can spare significant number
of patients from unnecessary hormonal therapy. Also, elimination of primary tumor might be useful to avoid
or defer androgen deprivation therapy. This later might be translated into positive influence on survival
rates of metastatic PC patients.
155
Unmoderated Posters
Introduction & Objectives: Radical prostatectomy (RP) is seldom a therapeutic consideration in men with
clinically-evident regional or distant metastatic prostate cancer (PC). This practice is based on the belief
that the surgical removal of the prostate offers no benefit to men with pre-existing metastatic disease.
Retrospective data suggest that in selected men, RP although not curative, may prolong survival of pathologically metastatic PC men. Our aim was to examine feasibility and potential survival benefit of radical
prostatectomy in selected clinically metastatic prostate cancer patients.
P117
The use of sequential abiraterone and cabazitaxel in castrate resistant prostate cancer Experience from a UK centre
Fackrell D.G., James N.D.
University Hospital, Dept. of Oncology, Birmingham, United Kingdom
Introduction & Objectives: Large, randomised phase III studies carried out simultaneously have shown
both abiraterone (Abi) and cabazitaxel (Cbz) to have a survival benefit in patients following docetaxel treatment for metastatic castrate resistant prostate cancer (mCRPC). Their use sequentially is less recognised.
We present data from patients that have received both therapies.
Unmoderated Posters
Material & Methods: We searched our pharmacy database for patients exposed to either Abi or Cbz
and identified 7 patients who had received both drugs. A detailed notes review was carried out of these
patients.
Results: Median age was 65 (range of 57-76) years. All patients had received hormone androgen deprivation therapy and docetaxel. Six patients reported a good clinical response to Cbz with improvement in
symptoms such as pain as well as performance status. Three of these patients had a poor response to
Abi in terms of time to progression (TTP). One patient responded very well to both drugs (TTP 23 mo Abi
and 12 mo Cbz) while two patients that had a poor response to Abiraterone also had a poor response to
Cabazitaxel (5 and 2 months respectively). Thus the response to one of the drugs was not a good predictor
of response to the other. Median time to progression from starting one treatment to progressing on the
second was 66.8 weeks. Five of the 7 patients were still alive after 33 weeks and 2 were alive after 62
weeks.
Patient
Time to Progression on
Abiraterone (months)
Time to Progression on
Cabazitaxel (months)
Overall Survival (months)
1
23
12
38+
2*
1.5
3.5
6
3*
6
6**
12+
4
5
2
10
5
5
2
7.5
6
6
4+
10+
7
5
3+
8+
+ time to end point not yet reached
* Patient received Cbz followed by Abi, all other patients received Abi then Cbz
** Patient did not progress on Cbz. Treatment stopped due to intolerance
Conclusions: Although this is a small sample, TTP was at least 3.5 months on Cbz which compares
favourably with the TROPIC trial with TTP of 2.8 months. In addition, 1 patient experienced a very long
TTP of around a year. Thus there is no evidence that prior exposure to Abi precludes clinical benefit from
treatment with Cbz. Furthermore, lack of response to one drug did not preclude worthwhile response to the
other agent, consistent with the two drugs having distinct mechanisms of action. On this limited data set
we conclude that sequential use of both Abi and Cbz may be appropriate in selected patients.
156
P118
Preliminary results of HOPLITE trial, a factorial phase II randomized trial of continuous (C) or
intermittent (I) docetaxel (D) В± estramustine (E) as first line treatment for castration resistant
prostate cancer (CRPC)
Caffo O.1, Lo Re G.2, Sava T.3, Buti S.4, Sacco C.5, Basso U.6, Zustovich F.6, Martini T.7, Perin A.8, Veccia A.1,
Russo L.M.1, Facchini G.9, Barile C.10, Gernone A.11, De Vivo R.12, Pappagallo G.13, Galligioni E.1
Santa Chiara Hospital, Dept. of Medical Oncology, Trento, Italy, 2Santa Maria Degli Angeli Hospital, Dept.
of Medical Oncology, Pordenone, Italy, 3Civil Hospital, Dept. of Medical Oncology D'O, Verona, Italy, 4Civil
Hospital, Dept. of Medical Oncology, Cremona, Italy, 5Santa Maria Della Misericordia Hospital, Dept. of
Medical Oncology, Udine, Italy, 6I O V, Dept. of Medical Oncology, Padua, Italy, 7Civil Hospital, Dept. of
Urology, Bolzano, Italy, 8Civil Hospital, Dept. of Medical Oncology, Thiene, Italy, 9N C I, Dept. of Urological
Oncology, Naples, Italy, 10Civil Hospital, Dept. of Medical Oncology, Rovigo, Italy, 11Civil Hospital, Dept. of
Medical Oncology, Bari, Italy, 12Civil Hospital, Dept. of Medical Oncology, Vicenza, Italy, 13ULSS 13, Dept. of
Epidemiology and Clinical Trials, Mirano, Italy
Introduction & Objectives: C administration of D (8-10 consecutive courses) is usually considered as a
standard treatment as first line for CRPC pts. An I administration could improve pts compliance and quality
of life (QL). E is an old drug showing a synergistic action with D. This study is aimed to compare QL of C
and I D and whether E added to D improved its activity, in a 2 Г— 2 factorial design.
Material & Methods: CRPC pts were randomized to: C D 70 mg/m2 IV q 3 wks for 8 courses alone (arm
A) or with E 280 mg/TID PO for 5 days starting 1 day prior to D (arm B), or the same treatments given with
a 3-month rest period after the first 4 courses (arm C and D, respectively). The primary end points were QL
(EORTC QLQ C30 and BPI) of A+B vs C+D and 1-y PFS (according to PCWG2) of A+C vs B+D.
Results: 148 CRPC pts were enrolled from 11/06 to 10/10 with 130 pts evaluable at this time. The
median age was 69 (range 42-81) and the median baseline PSA was 55.6 (range 0.33-4212). The major
hematological toxicities were: anemia G3 (3 pts), neutropenia G3 (4 pts) – G4 (5 pts), febrile neutropenia
(5 pts). Comparing C and I, QL outcomes were not statistically different in terms of general QL items.
Comparing D and DE, 1-y PFS was superimposable (10.3% and 13.2%, respectively). The 2-y overall survival
was not different between I and C arms 41.5% and 50.7% respectively) and between D and DE arms (41.9%
and 53.2% respectively).
Conclusions: These preliminary results suggest that I treatment did not produce a QL advantage
compared to C treatment, while the addition of E to D did not improve 1-y PFS of CRPC pts. Updated data
with the complete sample analysis will be presented.
157
Unmoderated Posters
1
P119
Expansion of pelvic lymph node dissection enhances survival in prostate cancer patients with
minimal lymph node invasion
Alekseev B.Y.1, Nyushko K.M.1, Vorobyev N.1, Frank G.A.2, Andreeva Y.Y.2, Chissov V.I.3, Andrianov A.N.1
1
Moscow Hertzen Oncology Institute, Dept. of Oncourology, Moscow, Russia, 2Moscow Hertzen Oncology
Institute, Dept. of Pathology, Moscow, Russia, 3Moscow Hertzen Oncology Institute, Dept. of Oncology,
Moscow, Russia
Unmoderated Posters
Introduction & Objectives: The aim of the study was to evaluate biochemical recurrent-free survival
(RFS) in intermediate and high risk prostate cancer patients with minimal lymph node (LN) invasion who had
undergone radical prostatectomy (RPE) with extended pelvic lymph node dissection (E-PLND).
Material & Methods: We analyzed database of 595 patients who had undergone RPE and PLND in our
institution since 2006 till 2011. 262 consecutive intermediate and high risk PC patients were included
in further analysis. Patients with extensive LN metastases who received adjuvant hormonal treatment
were excluded from the analysis. Mean patient’s age was 67.8±6.47 (46-77) years; mean PSA level was
14.8В±10.7 (1.5-79.0) ng/ml. Mean number of LN removed was 24.96В±7.6 (15-52). Morphological stage
pТ2а-Т2с was verified in 146 (55.7%) patients, pТ3а-Т4 – in 116 (44.3%). pN0 was found in 199 (76.0%); 1
or 2 LN metastases were found in 34 (12.9%); > 2 – in 29 (11.1%) patients. Morphological Gleason score
2-4 was in 3 (1.1%) patients, 5-6 – in 129 (49.2%), 7– in 100 (38.2%), 8-10 – in 24 (9.2%) patients. In 6
(2.3%) patients Gleason score was not assessed. Median follow-up (FU) time was 21.4В±15.4 (6-73) months.
Results: During FU period recurrences were observed in 74 (28.2%) patients. In subject to number of LN
metastases revealed recurrences were diagnosed in 33 (16.6%), 17(50%) and 24 (82.6%) patients with 0,
1-2, and > 2 metastases respectively (p<0.05). Cumulative 3-year RFS was 85.4В±3%; 44.96В±10.7% and
22.6В±8.5% in groups respectively (p<0.0001). Morphological stage, Gleason score and PSA level
correlated with probability of PSA relapse after surgery (p<0.0001).
Conclusions: RFS significantly differed in groups of patients with no metastases, 1-2 metastases and > 2
metastases revealed. 3-year RFS rate in patients with 1-2 LN metastases was 45%, thus this patients could
be candidates for delayed hormonal treatment.
158
P120
Lymph node involvement in prostate cancer after laparoscopic pelvic lymph node dissection
Van Dooren V.P.M., Fossion L.M.C.L., Van Aarle S., Brandenburg J.J.I., Nanlohy-Manuhutu E.L., Levens W.,
De Laet K., Braam P.
MГЎxima Medical Centre, Dept. of Urology, Veldhoven, The Netherlands
Material & Methods: The study included 395 patients with prostate cancer treated between January
2000 and May 2012 in a general community hospital. In all patients pre-operative prostate specific
antigen, clinical stage and Gleason grade were recorded. With this data predictions of the Partin Tables
and Briganti Nomogram were calculated. Patients underwent a laparoscopic pelvic lymph node dissection
(LPLND) according to the extended LPLND template and one of the following therapies: laparoscopic
prostatectomy, external beam radiation therapy, brachytherapy, hormonal therapy and HIFU therapy. LNI
was recorded for all patients. We calculated the area under the curve (AUC), using receiver operating
characteristic (ROC) analysis, to asses the discriminating accuracy of the Updated Partin Tables and the
2006 Briganti Nomogram.
Results: The mean number of lymph nodes removed was 11 (SD В±6.2) and LNI was seen in 73 (18.5%)
of the 395 patients (Table 1). None of the patients in the EAU low risk group had LNI. In the intermediate
risk group 13 (8%) patients had LNI, in the high risk group 59 (30.7%) patients had LNI. The discriminating
accuracy of the Updated Partin Tables, expressed in AUC, was 75% in our cohort. The discriminating
accuracy of the Briganti nomogram, expressed in AUC, was 76% in our cohort.
Conclusions: Due to population differences, stage and grade migration, bias of clinical staging and bias
of pathologic staging, external validation of predictive tools is necessary to asses their usability in different
hospital settings and different patient populations. The Updated Partin Tables and the Briganti Nomogram
are adequate in predicting LNI in a Dutch cohort.
159
Unmoderated Posters
Introduction & Objectives: Due to stage and grade migration and differences between populations
predictive tools need external and periodic validation to ensure their usability. To our knowledge the
accuracy and performance characteristics of the 2007 Partin tables and the 2006 Briganti nomogram
have not been validated in an external Western European cohort. In this article we will present a table
showing LNI in our cohort and we will analyze the accuracy of The 2007 Partin Tables and The 2006
Briganti Nomogram in our Dutch cohort.
P121
Prediction of response to androgen deprivation therapy and castration resistance in primary
metastatic prostate cancer
Divrik R.T., TГјrkeri L., Ећahin A.F., AkdoДџan B., AteЕџ F., Г‡al Г‡., BaltacД± S.
Marmara University School of Medicine, Dept. of Urology, Istanbul, Turkey
Introduction & Objectives: We aimed to establish the predictive factors influencing the initial response,
as well as its duration, and time to castration resistance (CR) for primary advanced prostate cancer (PC)
patients with bone metastasis (BM) who received androgen deprivation therapy (ADT).
Unmoderated Posters
Materials & Methods: We evaluated all patients initially receiving ADT for primary advanced prostate
cancer with bone metastasis. A total of 982 patients with complete medical records available for analysis
from 18 centres were included in this study. Age, initial PSA, Gleason sum (GS) and extent of bone
involvement (EBI) were recorded in a database.
Results: Among all patients, 896 (91.2%) responded to ADT initially. Pre-treatment PSA and EBI were
significant predictors in multivariate model. Among the 659 patients who progressed in to a CR state, the
mean duration of response was 22.4 months. There was a significant correlation between the CR state and
nadir PSA (nPSA) level and time to nPSA (TTnPSA). Pre-treatment PSA, EBI, GS, highest tumour volume in
biopsy cores (%), number of positive biopsy cores, percent positive biopsy cores and time to nPSA were В all
significant predictors of nPSA. Pre-treatment PSA, GS and EBI were statistically significant predictors of
PSA normalization in multivariate analysis. The limitations of this study are the retrospective nature in
design and the possible case selection bias by use of multicenter data. Patients enrolled in this study were
also from a relatively long period of time (1989 to 2008).
Conclusions: Results of this study indicate that it is possible to predict the initial response to ADT by
pre-treatment PSA levels and EBI, while the duration of response can be reflected by a multitude of clinical
factors including nPSA, TTnPSA, percent positive cores, biopsy GS and EBI.
160
P122
Radical laparoscopic prostatectomy for locally advanced disease
Brandenburg J.J.I., Fossion L.M.C.L., Van Aarle S., Van Dooren V.P.M., De Laet K.
MГЎxima Medical Centre, Dept. of Urology, Veldhoven, The Netherlands
Material & Methods: From May 2006 to February 2012 we performed 240 EERPE’s in men with PCa.
Based on guidelines and nomograms, a laparoscopic lymph node dissection (LPLND) was performed in 164
cases (69%) using the current extended template. All procedures were performed by the same surgeon.
Information regarding operating time, blood loss, hospital stay, catheterization time, pathological data
and functional outcome were collected prospectively in our patient database. We retrospectively analyzed
the charts of 78 patients (32,5%) with confirmed locally advanced disease for further information on
preoperative staging, complications and mid-term oncological follow-up. We used SPSS 20.0 to calculate
Kaplan-Meier curves for biochemical progression-free survival. For statistical analysis we used the chisquare- and log rank test. PSA recurrence was defined as a rise of PSA above 0,2 ng/mL in at least 2
consecutive laboratory tests.
Results: In the locally advanced group 45 patients were staged as pT3a (18,8%), 32 pT3b (13,3%) and 1
pT4 (0,4%). In table 2 we highlight the comparison between surgical margins and pathological stage. Table
3 shows clincal over- and understaging in 23,5% and 25,2% respectively. In the locally advanced group, 43
preoperative MRI’s were made in an attempt to stage PCa more accurately. With the use of this modality
there still was understaging in 26 of 43 patients (60,5%). Prediction of lymph node invasion (LNI) with MRI
also was difficult (table 4). Thirty-three postoperative complications occurred in 30 patients (table 5) including 4 colostomies because of rectal injury and subsequent sepsis or fistula (Clavien 3b). No perioperative
mortality was noted. Mean follow up of the study was 30,5 months (range 3-61). During this period of time
2 patients died, 1 as a result of PCa (CSS 97,5%). Three year biochemical progression-free survival (BPFS)
was 55%. Subgroup analysis showed a significant difference in BPFS between LN+/LN- and pT3a/pT3b
(p<0,05) (figures 1-4). No significance was reached for surgical margins.
161
Unmoderated Posters
Introduction & Objectives: Recent data from European and US studies provide an estimation of the incidence of cT3-4 PCa, which is thought to be 10-20%. The optimal treatment for cT3 PCa has been subject to
debate during recent years. Our aim is to better define the place of surgery in locally advanced disease.
Unmoderated Posters
Table 2. Comparison between positive surgical margins Table 3. Clinical over- and understaging. Staging based on
and pathological stage after laparoscopic prostatectomy
digital rectal examination, ultrasound and occasionally MRI.
Table 4. Value of MRI in predicting LNI. Sensitivity 0,10, s
Table 5. Postoperative complications according to the
pecifity 0,90, PPV 0,17, NPV 0,76. LNI=lymph node invasion,
Clavien-Dindo classification.
PPV=positive predictive value, NPV=negative predictive value
Conclusions: In our study locally advanced PCa’s have a higher iPSA-level, pathological Gleason score,
higher risk of lymph node invasion and positive surgical margins. Preoperative staging remains difficult,
even with the use of MRI. Oncological results are promissing especially for pT3a PCa without lymph node
invasion. Therefore efforts have to be made for better patient selection. In case of positive surgical
margins and rising PSA, salvage EBRT/IMRT seems beneficial.
162
P123
What women know about testicular cancer? - Exploratory study of a female university
population
Campos Braga I.L.1, Louro N.R.2, Cabral J.F.2, Lafuente De Carvalho J.M.2, Fraga A.2
Life and Health Sciences Institute - University of Minho - Braga; Hospital Center of Porto, Dept. of
Urology, Porto, Portugal, 2Hospital Center of Porto, Dept. of Urology, Porto, Portugal
1
Material & Methods: We performed a survey of 13 questions concerning the awareness of TC and
perceived importance of testicular self-examination in 307 women from the university. The questionnaire
was sent to the institutional email of students, professors and other workers and the data were collected
and then analyzed.
Results: The mean age of our group was 26В±8,3 years (range 18-58 years). Students were 74,6% (n=229)
of the sample and 25,7% (n=79) were from the medical course. When asked if they had any knowledge
about TC, 89,3% (n=274) answered they had information about TC. Sixty four (20,8%) of the participants
knew someone with testicular cancer.Only 25% (n= 77) of the women answered correctly to the question
about the age group most frequently seen with TC and 57,7% (n=177) responded properly to the most
frequent symptom of testicular cancer. When a paired analysis of the correct answers to the age group of
TC and most frequent symptom only 24 (7,8%) of the subjects gave proper responses to every questions.
A second part of the questionnaire was about testicular self-examination. Approximately half (50,5%)
of the subjects, n=155, referred knowledge about testicular examination. We used a Lickert-type scale
to categorize the perceived importance of this examination from 1 (not important) to 10 (extremely
important), with 69,4% (n=213) considering that this was extremely important (10) and only one participant
(0,3%) responded that it wasn’t important. Almost all participants (95,4%) answered that they would advise
their male friends to perform testicular self-examination.
Conclusions: In this study we have showed a low level of knowledge about TC. Despite this fact, the
knowledge about this cancer, a great number of women considered important to men to perform testicular
self-examination and were motivated to advise their male friends to perform it. Considering that partners
may assume an important role in health promotion and education, maybe women, as the partner of
patients in risk of having TC, can be a way of engaging healthy behaviors in men.
163
Unmoderated Posters
Introduction & Objectives: Testicular cancer (TC) is one of the most common malignancies in young
population, and it appears to be increasing worldwide. The cure rate for TC now approaches 100%, but is
negatively influenced by the delay in seeking medical attention. Sometimes it’s a man’s partner who spots
a change in the testicle. Several publications have showed the importance of the partners in health. There
is a lack of evidence about the importance of women, as partners, in the diagnosis of several pathologic
processes in men, but we know that the healthy behavior is shaped by the partner. Our objective was to
evaluate women’s knowledge about TC, as they can act as educators towards better men’s health.
P125
Excellent long-term disease control with modern radiotherapy techniques for stage I testicular
seminoma – the Mayo Clinic experience
Hallemeier C.L.1, Choo R.1, Davis B.J.1, Leibovich B.C.2, Costello B.A.3, Pisansky T.M.1
Mayo Clinic, Dept. of Radiation Oncology, Rochester, United States of America, 2Mayo Clinic, Dept. of
Urology, Rochester, United States of America, 3Mayo Clinic, Dept. of Oncology, Rochester, United States of
America
1
Unmoderated Posters
Introduction & Objectives: The purpose of this study was to examine the long-term efficacy and adverse
effects of adjuvant radiotherapy (RT) for stage I testicular seminoma.
Material & Methods: A retrospective review was performed of 199 patients with stage I testicular seminoma treated with curative intent orchiectomy and adjuvant megavoltage RT at our institution from January
1, 1972 through December 31, 2009. CT staging was performed for 90% of patients. No patient received
mediastinal RT or adjuvant chemotherapy. Overall survival (OS), cause-specific survival (CSS), relapse rate,
major cardiac event (MCE), and second malignancy (SM) were estimated using the Kaplan-Meier method.
Results: The median patient age was 36 years (range: 18-80). The nodal regions irradiated were the paraaortic and ipsilateral pelvic nodes in 147 patients (74%), the para-aortic nodes alone in 34 (17%), and the
para-aortic and bilateral pelvic nodes in 18 (9%). The median RT dose was 25.5 Gray (interquartile range:
25-30). The median follow-up after RT was 13 years (range: 0.1-37). OS at 10 and 20 years were 92% and
77%, respectively. CSS at 10 and 20 years were both 99%. Risk of relapse at 10 and 20 years were 1 and
2%, respectively. Risks of MCE and SM at 20 years were 12% and 19%, respectively.
Conclusions: Our series confirms an excellent outcome in patients with stage I testicular seminoma
treated with RT. Relapse after adjuvant RT is very uncommon, but late morbidity associated with RT may
occur.
164
P126
Patients with penile cancer and a history of herniorrhaphy – does lymphatic drainage change?
Ciudin A., Diaconu M.G., Corral J.M., Huguet J., Ribal M.J., Alcaraz A.
Hospital Clinic Barcelona, Dept. of Urology, Barcelona, Spain
Introduction & Objectives: The dynamic sentinel node biopsy (DSNB) using Tc99m-colloid sulphurin in
penile cancer is a useful tool to reduce the morbidity associated with extensive inguinal lymphadenectomy.
Our objectives to assess in our series of patients with penile cancer that underwent diagnosis by the
technique of DSNB if there are changes in the lymphatic drainage in those patients with a history of
surgical repair of inguinal hernia.
Results: Between January 1999 and December 2010 a total of 35 patients have been treated for penile
cancer in our center. Diagnosis by means of DSNB was indicated and performed in 19 patients. All DSNB
patients had clinical T1/T2 tumors without palpable lymph nodes.Of all the patients that underwent
DSNB, 7 had a history of open surgery hernia repair. The lymphatic drainage and the sentinel node (SN)
of these patients according to the scintigraphic findings were:- to the inguinal group alone in 2 cases that
had unilateral hernia repair one being negative and one positive. - to both inguinal and inferior anterior
abdominal wall lymph nodes (IAAWL) in 3 cases. There was performed a sampling of both areas. All
SN were negative. - to IAAWL alone in two cases. All SN were negative. The side of IAAWL involvement
corresponded with the side of the previous hernia repair in all patients. All 12 patients without a history of
open herniorrhaphy showed lymph drainage to the inguinal lymph nodes.
Conclusions: Open surgery for inguinal hernias might cause a change in the penile lymph drainage.
In these patients drainage to the IAAWL has been identified. If Tc99m drainage is identified to both the
inguinal nodes and IAAWL both areas should be sampled while performing DSNB.
165
Unmoderated Posters
Material & Methods: We performed a retrospective review of our database of patients with penile
cancer. Clinical history, evolution, the need for diagnostic DSNB and outcomes were evaluated. DSNB was
performed at the same time as the penile surgery.
166
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Company Profiles
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ACCURAY
22 place des Vosges, 3e Г©tage, 92400 Courbevoie, France
T : +33 15523 20 20
F : +33 15523 20 39
W: www.accuray.com
Accuray is the premier radiation oncology company that develops, manufactures and sells personalized
innovative treatment solutions that set the standard of care, with the aim of helping patients live longer,
better lives. The Company’s leading-edge technologies – the CyberKnife and TomoTherapy Systems –
are designed to deliver radiosurgery, stereotactic body radiation therapy, intensity modulated radiation
therapy, image-guided radiation therapy and adaptive radiation therapy.
Bayer Healthcare AG
W: www.bayer.com / www.bayerpharma.com
Bayer HealthCare Pharmaceuticals is the pharmaceutical division of Bayer HealthCare AG. We market
our products in more than 100 countries, and in 2011 generated sales of almost € 10 billion. More than
37,000 members of staff currently work for Bayer HealthCare Pharmaceuticals worldwide – more than
6,500 in research and development alone. We aim to improve people’s quality of life with our products. To
achieve this, we concentrate on the research and development of innovative drugs and novel therapeutic
approaches. At the same time, we are constantly improving established products. In this context, Bayer
HealthCare Pharmaceuticals uses experience it has gained from over a century in the business. We
concentrate on four big therapeutic groups in which we make essential contributions to medical progress:
- Cardiovascular and blood diseases
- Oncological diseases
-Ophthalmology
- Women’s healthcare
DENDREON CORPORATION
1301 2nd Avenue, Suite 3200, Seattle, Washington 98101, United States of America
T : +1 8772 564 545
F : +1 2062 560 571
W : www.dendreon.com
Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform
lives through the discovery, development and commercialization of novel therapeutics. The Company
applies its expertise in antigen identification, engineering and cell processing to produce active cellular
immunotherapy product candidates designed to stimulate an immune response.
169
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ASTELLAS PHARMA EUROPE LTD.
2000 Hillswood Drive, Chertsey, Surrey, KT16 0RS, United Kingdom
T : +44 203 379 8700
W: www.astellas.eu
Astellas has made a commitment to change tomorrow – a commitment that we are bringing to the field of
oncology. We aim to create innovative treatments that will genuinely improve the lives of cancer patients.
To do this we are focusing our R&D and partnership efforts into precision medicine that will create first-inclass or best-in-class programmes. This has resulted in no fewer than 12 separate therapies under clinical
development into conditions including prostate cancer, other solid tumours like pancreatic cancer, breast
cancer and advanced renal cell carcinoma, as well as haematological malignancies.
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ELEKTA
Kungstensgatan 18, Box 7593, SE- 10393 Stockholm, Sweden
T : +46 8587 25 400
F : +46 8587 25 500
W: www.elekta.com
E: [email protected]
Elekta is a human care company pioneering significant innovations and clinical solutions for treating cancer
and brain disorders. The company develops advanced tools and treatment planning systems for brachy
therapy, radiation therapy and radio surgery, and workflow enhancing software systems across the cancer
care spectrum. Through its products and services, Elekta aims to improve, prolong and save patient lives.
Elekta solutions in oncology and neurosurgery are used in over 6,000 hospitals globally, and daily more
than 100,000 patients receive diagnosis, treatment or follow-up with the help of an Elekta Group solution.
Elekta, with corporate headquarters in Stockholm, Sweden, employs approximately 3,300 people globally.
EUROPEAN ASSOCIATION OF UROLOGY (EAU)
Mr. E.N. van Kleffensstraat 5, 6842 CV Arnhem, the Netherlands
T : +31 2638 906 80
F : +31 2638 906 74
W : www.uroweb.org
E : [email protected]
Founded in 1972, the European Association of Urology (EAU) is now entering its fourth decade; a period
marked by growth in its membership with the goal to create a dynamic network of medical professionals.
Membership has been extended and is now open to urologists-in-training, urological scientists and to
related disciplines in Europe and abroad.
All registered European urologists, European urologists-in-training and medical professionals in affiliated
fields are eligible for EAU membership. Joining the EAU is not only about European urology; it is also about
enhancing and ensuring the future of our speciality with the ultimate goal to provide the best patient care.
To learn more about the EAU and its membership, visit www.uroweb.org.
EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY (ESMO)
via L. Taddei 4, 6962 Viganello-Lugano, Switzerland
T : +41 9197 31 900
F : +41 9197 31 902
W: www.esmo.org
E: [email protected]
ESMO is the leading European professional organization committed to advancing the specialty of medical
oncology and promoting a multidisciplinary approach to cancer treatment. ESMO is committed to good
science that leads to better medicine and determines best practice.
ESMO represents a community of over 7,000 oncology professionals from over 120 countries.
170
EUROPEAN SOCIETY FOR RADIOTHERAPY & ONCOLOGY (ESTRO)
Rue Martin V 40, 1200 Brussels, Belgium
T : +32 2775 93 40
F : +32 2779 54 94
W : www.estro.org
E : [email protected]
Founded in 1980, ESTRO, the European Society for Radiotherapy and Oncology, is a non-profit and
scientific organisation that fosters the role of Radiation Oncology in order to improve patients’ care in the
multimodality treatment of cancer. With over 5000 members in and outside Europe, ESTRO supports all
the Radiation Oncology professionals in their daily practice: Radiation Oncologists, Medical Physicists,
Radiobiologists and RTT (Radiation TherapisTs) and the wider Oncology community. ESTRO’s mission is
to promote innovation, research, and dissemination of science through its congresses, special meetings,
educational courses and publications.
More information on www.estro.org
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WISEPRESS MEDICAL BOOKSHOP
25 High Path, London, SW19 2JL, Great Britain
T : +44 208715 18 12
F : +44 208715 17 22
W : www.wisepress.com
E: [email protected]
Wisepress.com, Europe’s leading conference bookseller, has a complete range of books and journals
relevant to the themes of the meeting. Books can be purchased at the stand or, if you would rather not
carry them, posted to you.
171
172
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About the Organisers
European Association of Urology (EAU)
European Society for Medical Oncology (ESMO)
Organisers
European Society for Radiotherapy & Oncology (ESTRO)
173
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Organisers
About the European Association
of Urology (EAU)
A vibrant network of urological professionals
Founded in 1972, the European Association of Urology (EAU) is now entering its fourth decade, a period
marked by growth in its membership, thanks to the efforts made in the mid-1990s to modernise the EAU’s
structure and widen its activities.
With the goal to create a dynamic network of medical professionals, membership has been extended and
is now open to urologists-in-training, urological scientists and to related disciplines in Europe and abroad.
Moreover, the EAU has increased the number of EAU activities that could be of benefit to other medical
professionals. Today, the estimated number of practicing urologists in Europe is at 16,000, a significant
and fast-growing medical community in which the EAU aims to be a leading partner in discussions that
impact on global urological affairs.
Facilitating growth
With the crucial goal to enhance patient care, the EAU’s cores mission is to act as the representative
body for all European urologists, thus facilitating the continuous development of urology and all its
subspecialties. In order to maintain the high standards of urological care throughout Europe, the
EAU stimulates urological research and helps disseminate the results. Another key goal is promoting
contributions by its members to medical and scientific literature, thereby highlighting European urological
achievements. The EAU also focuses on establishing training and urological practice standards and help
contribute in defining European urological health care policies.
Committed involvement
Over one hundred European urologists are involved in the boards of the EAU Offices and Committees who
all meet periodically to assess the strategies and plans mapped out within the EAU. As administrative body,
the EAU Central Office, supports the EC and the EAU offices. An Executive Management team supervises
the EAU Central Office with the Operational Manager (Jacqueline Roelofswaard) directing and organising
all operational affairs of the EAU Central Office and the Business Manager (Maurice Schlief) implementing
the financial and business plans. Located in Arnhem, the Netherlands, the EAU Central Office employs
approximately 55 staff.
Active representation
The General Assembly, held annually as the official meeting for EAU members coincides with the Annual
EAU Congress. All active EAU members can exercise their vote at the General Assembly where decisions
are made by a majority of votes from all who are present. The General Assembly also votes or approves
new and honorary members of the EAU, elect members of the EC and nominates new board members.
Fulfilling key tasks
Education and postgraduate training are essential tasks of the EAU. With the aim to promote quality
urological education across Europe, the EAU’s education programmes are easily accessible and affordable
to all European urologists and urologists-in-training. Strategies and goals for education are developed,
175
Organisers
A centralised structure
The EAU’s governing structure is the EAU Board composed of an Executive Committee (EC) and the chairs
of the EAU Offices. Chaired by the Secretary General Per Anders Abrahamsson and together with the other
EC members, the EC oversees the implementation of all programmes and activities. Constituting the current
EC are Hein van Poppel, Manfred Wirth and Walter Artibani who all lend their support to the EAU Secretary
General.
organised and supervised by the European School of Urology (ESU), the EAU’s official education office. The
ESU organises courses during the Annual EAU Congress and in collaboration with the European National
Urological Associations.
A key task of the EAU is to support scientific activities. The Scientific Congress Office prepares the
scientific programme of the Annual EAU Congress and its aim is to ensure a high quality level programme.
Research fellowship programmes are funded through the European Urological Scholarship Programme
(EUSP). Recently, the EAU has also set up a Foundation for Urological Research which aims to serve as a
dynamic link between the industry on one hand and scientific and medical research communities on the
other hand.
Communicating achievements
Providing effective communication links to promote and disseminate scientific results and information
amongst European urologists remains vital. European Urology is the EAU’s official scientific journal, widely
disseminated and highly regarded by readers. The EAU Video Committee is the editorial body responsible
for the European Urology Video Journal, which distributes selected new videos on urological diseases and
techniques.
The official EAU newsletter, European Urology Today, publishes a range of information on European urology
and activities as well as specialised information provided by affiliated European urological associations and
organisations. Finally, the EAU maintains dedicated Internet sites such as Uroweb (www.uroweb.org), which
provides general information resources to members, and Urosource (www.urosource.com) which offers a
wide database of urological and scientific information.
Joining the EAU
All registered European urologists, European urologists-in-training and medical professionals in affiliated
fields are eligible for EAU membership. We are not only on the lookout for innovative talent but our doors
are also open to interested non-European urologists. Joining the EAU is not only about European urology; it
is also about enhancing and ensuring the future of our speciality with the ultimate goal to provide the best
patient care.
Organisers
To learn more about the EAU and its membership, visit www.uroweb.org.
For all upcoming EAU meetings visit www.uroweb.org/events/meeting-calendar.
176
About the European Society for
Medical Oncology (ESMO)
The European Society for Medical Oncology (ESMO) is the leading European professional organization,
committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to
cancer treatment and care.
Since its founding in 1975 as a non-profit organization, ESMO’s mission has been to advance cancer care
and cure. We achieve this through fostering and disseminating good science that leads to better medicine
and determines best practice. In this way ESMO fulfils its goal to support oncology professionals in
providing people with cancer with the most effective treatments available and the high-quality care they
deserve.
The ESMO community is a powerful alliance of more than 7,000 committed oncology professionals from
over 120 countries. As a trusted organization with 35 years of experience and over 500 expert committee
members, ESMO serves its members and the oncology community through:
•
•
•
•
Excellence in post-graduate oncology education and training
Leadership in transforming evidence-based research into standards of cancer care in Europe
Dedicated efforts to foster a more favorable environment for scientific research
Innovative international platforms to share expertise, best practices and disseminate the most
up-to-date scientific research to as wide an audience as possible.
ESMO has expanded its membership offering through OncologyPRO, an exclusive scientific and educational
website: http:\\oncologypro.esmo.org. ESMO’s scientific journal, Annals of Oncology, ranks among the top
clinical oncology journals worldwide. ESMO events are the meeting place in Europe for medical oncologists
to update their knowledge, network and exchange ideas. ESMO also unites key oncology stakeholders and
forges strategic partnerships to address critical issues related to the profession and practice of medical
oncology. Recognized as an authoritative voice in the fight against cancer, ESMO is pleased to offer
consultative expertise to oncology organizations and European authorities on important issues related to
cancer research, prevention, diagnosis, treatment and care.
Organisers
Join the ESMO community today! Please visit www.esmo.org to learn more.
177
About the European Society for
Radiotherapy and Oncology (ESTRO)
Founded in 1980, the European Society for Radiotherapy and Oncology, ESTRO, is a non-profit, scientific
organisation whose role is to foster, in all its aspects, radiation oncology, clinical oncology and related
subjects, including physics as applied to radiotherapy, radiation technology and radiobiology.
To fulfill its purpose, ESTRO:
• Develops and promotes standards of education in radiotherapy and clinical oncology;
• Promotes standards of practice in radiotherapy, clinical oncology and related subjects;
• Stimulates the exchange of scientific knowledge in all related fields;
• Strengthens the clinical specialty of radiotherapy and clinical oncology in relation to other specialties
and professions involved in cancer management;
• Encourages co-operation with international, regional and national societies and bodies representing
radiotherapy, clinical oncology and related subjects;
• Facilitates research and development in radiotherapy, clinical oncology and related subjects.
ESTRO 2013 Membership
ESTRO has revamped the content of its individual membership programme. A new set of categories are
now designed to provide the society’s members with relevant and cutting edge professional tools and
benefits:
Organisers
-Full membership 95 €: for active members with a complete offer of services that the society can offer.
New this year, ESTRO is developing a wide range of online services: through our new search engine, as
of January, the member will have access to a large library of documents such as abstracts of the Green
Journal, of conferences, webcasts, posters, educational courses material, free access to FALCON
(delineation tool), newsletters, etc…
- Associate: • In training 75 €: for all European professionals in the field of RO younger 35 years old, or with
relevant professional experience, or a University diploma emitted less than 5 years and in
training. Designed to create a wide access to ESTRO, this category will give, when eligible, the
same benefits that for the full member category except that the member won’t be eligible for
some positions within ESTRO (Board, councils, standing committees, etc).
• Affiliate: 55 €: the member will have access to a selection of offers which are mainly the access
to the Green Journal and reduction to access a conference or a teaching course once a year.
Also new for 2013, ESTRO has created the institutional membership: each institute can buy several
individual memberships and get some specific benefits such as packages for online workshops, a
dedicated corner in the Newsletter, ability to distribute standards/guidelines within the organisation and
much more.
More information on www.estro.org
178
ESTRO Next annual meetings
2nd ESTRO Forum
19-23 April 2013 / Geneva, Switzerland
The scientific programme will bring together the following, previously individually held, meetings:
- Clinical & Translational Meeting
- GEC-ESTRO-ISIORT Meeting
- Physics Biennial Meeting
- RTT Meeting
- New in 2013: PREVENT (Prediction, Recognition, Evaluation and Eradication of Normal Tissue
effects of radiotherapy). Conference will also be part of the Forum.
ESTRO 33

4-8 April 2014 / Vienna, Austria
ESTRO School
In 2013, ESTRO will organise 35 live courses, in European and non-European countries that will attract
3000 participants from all over the world.
The Society has also developed for a few years a couple of e-learning tools. Developed by ESTRO, FALCON
(Fellowship in Anatomic deLineation and COntouriNg) can help to improve the contouring and delineation
skills that professionals of Radiation Oncology use in their daily practice.
Calendar of the 2013 school courses:
Spain
2-6 February
ESTRO/EANM educational seminar on PET in
Radiation Oncology
Brussels
Belgium
8-9 February
Dose modelling and verification for external beam
radiotherapy
Florence
Italy
10-14 March
Radiotherapy with protons and ions
Pavia
Italy
10-14 March
Physics for clinical radiotherapy
Izmir
Turkey
17-21 March
Evidence and new challenges in rectal cancer
Istanbul
Turkey
21-24 March
Modern brachytherapy techniques
Athens
Greece
24-27 March
Evidence-based radiation oncology: a clinical
refresher course with a methodological basis
Beijing
China
7-11 April
Pre-meeting courses at 2nd ESTRO FORUM
Geneva
Switzerland
19-Apr
Basic clinical radiobiology
Poznan
Poland
5-9 May
Multidisciplinary management of breast cancer
Prague
Czech Republic
11-14 May
Combined drug-radiation treatment: biological basis,
Porto
current applications and perspectives
Portugal
24-27 May
IMRT and other conformal techniques in practice
Stockholm
Sweden
26-30 May
Multidisciplinary teaching course on lung cancer
Krakow
Poland
6-8 June
Brachytherapy for prostate cancer
Cologne
Germany
6-8 June
Target volume determination - from imaging to
margins
Ljubljana
Slovienia
9-13 June
Multidisciplinary management of head and neck
oncology
Budapest
Hungary
30 June - 3 July
Image-guided radiotherapy & chemotherapy
in gynaecological cancer – focus on adaptive
brachytherapy
Moscow
Russian
Federation
30 June - 4 July
Physics for clinical radiotherapy
Cartagena
Columbia
24-28 July
Organisers
Multidisciplinary teaching course on prostate cancer Madrid
179
Clinical practice and implementation of imageguided stereotactic body radiotherapy
Lille
France
1-5 September
Advanced technologies
Amman
Jordan
5-9 September
Image-guided radiotherapy and chemotherapy
in gynaecological cancer – focus on adaptive
brachytherapy
Barcelona
Spain
8-12 September
Advanced imaging course for physicists
Vienna
Austria
8-12 September
Advanced treatment planning
Utrecht
The Netherlands
8-12 September
Basic treatment planning
Utrecht
The Netherlands
13-17
September
Quantitative methods in Radiation Oncology:
models, trials and clinical outcomes
Cambridge
United Kingdom
13-16 October
Target volume determination - from imaging to
margins
Bangkok
Thailand
20-23 October
Image-guided radiotherapy in clinical practice
London
United Kingdom
20-24 October
Multidisciplinary management of head and neck
oncology
Indore
India
27-30 October
Best practice in radiation oncology - A four phase
project train RTT Trainers. In collaboration with the
IAEA - Part II - Train the RTT trainers – consolidation
phase
Vienna
Austria
28-30 October
ESOR/ESTRO course: multidisciplinary approach of
cancer imaging
Rome
Italy
7-9 November
Comprehensive quality management in radiotherapy
- Part II Quality assessment and improvement (new)
Prague
Czech Republic
9-12 November
Multidisciplinary management of central nervous
system tumours (NEW)
Brussels
Belgium
17-19 November
EANM/ESTRO educational seminar on PET in
Radiation Oncology
Vienna
Austria
22-23 November
Basic Clinical radiobiology (Endorsed by ESTRO)
Sydney
Australia
24-28 November
Paediatric radiation oncology
Brussels
Belgium
5-7 December
Organisers
More information on www.estro.org
180
Indices
Abstract Authors
Abstracts sorted per Topic
Indices
Faculty List
181
182
Indices
A.
Aareleid, T.
P134
Abad Gairin C.
P008, P041, P044
Abella V.
P001
Acebedo C.
P108
Afonin S.V.
P015
Aglietta M.
P047
Agus D.B.
P114
Ahmed M.
P103
Ahn H.K.
P048
Г„hrlund-Richter L.
P104
AkdoДџan B.
P121
Alcaraz A.
P006, P026, P028,
P032, P126
Alekseev B.Y.
O4, P023, P045,
P046, P056, P075,
P119
Algaba F.
P005
Alumkal J.J.
P115
Aluwini S.
P074
Alvisi M.F.
P066, P068, P085
Alyaev Y.G.
P007, P084
Amir Nicolau B.F.
P038
Amosov A.V.
P084
Andreeva Y.Y.
P075, P119
Andrianov A.N.
P023, P045, P046,
P056, P075, P119
Angelsen A.
O6, P092
Anton-Aparicio L.M.
P001
AntГєnez-Plaza P.
P016, P033
Apolikhin O.I.
P060, P061, P080
Arango O.
P053, P086
Arends T.J.H.
P021
Armand Lefevre L.
P058
Armstrong A.J.
O10
AteЕџ F.
P121
Ather M.H.
P024, P029
Atzori F.
O5
Autier P.
P052
Avuzzi B.
P066, P068
Azawi N.H.
P042
Azoury F.
P107
B.
Bacchiddu S.
Baiocchi C.
Baldazzi V.
Balig Fawwaz B.F.
Ballatore V.
P069
P069
O5
P034
P047
BaltacД± S.
Banerjee S.
Bangma C.
Baratelli C.
Barile C.
Barrio M.
Basch E.M.
Basic D.
Bassi P.F.
Basso U.
Bathen T.
Bedini N.
Bejar S.
Bellardita L.
Beltramo G.
BeltrГЎn C.
Benchikh El Fegoun A.
Bergantin A.
Berger R.
Berkenblit A.
Berkovic P.
Bertilsson H.
Bianchi L.C.
Biasoni D.
Bielsa O.
Binotto L.
Birgit B.
Blanchard P.
Blank L.E.C.M.
Boccardo F.
Boladeras A.
Bolzicco G.
Bonzano A.
Borre M.
Bossi A.
Bouaita M.
Bourhis J.
Boursi B.
Braam P.
Braeckman J.
Braga I.
Brajuskovic G.
Branco F.
Brandenburg J.J.I.
Bruce J.Y.
Bruins H.M.
Buti S.
P121
P011
P074
O5
P118
P008, P041, P044
O10
P022
O3, P009
P118
P092
P066, P068
P111
P068, P085, P089
P070, P071
P076, P108
P058, P083
P070, P071
P036
O4, P040
O12
O6, P092
P070
P066, P124
P053, P086
P069
O11
P107
O1
O5
P111
P069
P047
O9
P107
P058
P107
P036
P120
P052
P035
P098
P035
P020, P120, P122
P115
P021
P118
C.
Cabral J.F.
Caffo O.
P123
P106, P118
Indices
Abstract Authors
183
Indices
Cagna E.
Cai T.
Г‡al Г‡.
Calmel L.
Campos Braga I.L.
Campos Gracia C.
Cao Avellaneda E.
Capdevila Gonzalo M.
Cappa E.
Carducci M.
Carillo V.
Carrara M.
Carthon B.
Casanova J.
Casanova-Salas I.
Castagnola M.
Catania S.
Cavadas V.
Cedermark G.C.
Celia A.
Cerbone L.
Cerovic S.
Chernyaev V.
Chi K.N.
Chissov V.I.
Cho E.K.
Choo R.
Choudat L.
Christensen T.
Ciechowicz J.
Cinieri S.
Ciudin A.
Clark W.R.
Colecchia M.
Collado A.
Coman I.
Cordeiro E.
Corn P.G.
Corral J.M.
Cortvriend J.
Costello B.A.
Cotreau M.M.
Cozzarini C.
Crawford E.D.
Crippa F.
O8, P087
P043
P121
P107
P123
P008
P059
P008
P009
P036, P112
P091
O8, P095
P114
P051
P051
O3
P066, P085
P035
P104
P043
O5
P098
P015, P037
O10
P075, P119
P048
P125
P083
P042
P067
O5
P026, P028, P126
P114
P066, P124
P051
P079
P035
P115
P126
P073, P088
P125
P040
P091
P109
P002
D.
D’Agostino D.
D’Hont C.J.L.
Daidone M.G.
Dal Bianco M.
Daniel J.
P009
P073, P088
P002
O3
P035
184
Davis B.J.
Davits R.J.A.M.
Davydov M.I.
D’elia C.
De Backer T.
De Blas R.
De Braud F.
De Cobelli O.
De Coninck V.
De Laet K.
De Meerleer G.
De Vincenzo F.
De Vivo R.
Decaestecker K.
Degli Esposti C.
Del Carpio A.
Del Rosario Rodriguez V.
Delrue L.
Descovich M.
Di Lorenzo G.
Diaconu M.G.
Dimanovski J.
Divrik R.T.
Doizi S.
DomГ­nguez-Escrig J.
Dominique S.
Donegani S.
Donnini A.
Dumont R.
Dumortier C.
Dykstra K.
Dzamic Z.
P125
P078
P037
P043
P073, P088
P111
P002
P070
P052
P120, P122
O12
O5
P118
O12
P091
P111
P034, P038
O12
P095
O5
P026, P126
P057
P121
P083
P051
P083
P089
O2
P051
P058
P040
P022
E.
Egote A.K.
Eisen T.
Eisenberger M.
Engelen A.M.
Escaf S.
Escudero Bregante F.
Esquena S.
Esteves B.
P093
O4
P036, P112
P078
P005
P059
P018
O4, P040
F.
Facchini G.
Fackrell D.G.
Fadil Hechadi Y.
FalcГіn Barroso J.
Fanali C.
Favretto M.S.
Fellin G.
Fernandes J.
P118
P117
P008, P044
P034, P038
O3
P069
O8, P087, P106
P050
P032
P005
P051
P111
P008
O11
P001
P037
P009
P023
P043
O8, P087, P091
P094
O10
P004
O12
P020, P120, P122
P035, P123
P086
P075, P119
P053
P034, P038
Giusti G.
P043
Glukhov A.I.
P007
Glybochko P.V.
P007, P054, P084
Gnad-Vogt U.
O11
Golovashchenko M.P.
P023
GГіmez-Ferrer A.
P051
GГіmez GГіmez G.
P059
Gonzalez-Sala J.L.
P008, P041, P044
Goren M.
P099
Gottfried M.
P036, P112
Gottschalk A.
P095
Green J.S.A.
P055, P100, P101,
P103
Gribbestad I.
O6, P092
Grigorieva Y.E.
P007
Gross-Langenhoff M.
P097, P110
Gual J.
P041
Gual Frau J.
P008, P044
Guedea F.
P111
Gupta S.
P049
GutiГ©rrez GutiГ©rrez P.
P059
GuzmГЎn MartГ­nez-Valls P.
P059
G.
Gabriele P.
Galizia D.
Galligioni E.
Galvez GarcГ­a C.
Gandhi J.
Ganzha T.M.
Garcia I.
Garcia R.
Garcia-Cenador M.B.
Garcia-Rojo D.
Gardi M.
Gaspar S.
Gat Y.
Gausa Ll.
Gaya J.M.
Gayo J.
Geijsen E.D.
Gene Tous E.
George D.J.
Gernone A.
Giannatempo P.
Gianni A.M.
Giese G.
Giganti M.O.
Gil-Vicente A.
Girelli G.
GiskeГёdegГҐrd G.
Gittelman M.C.
P087
P047
P106, P118
P034
P114
P084
P111
P050
P033
P008, P041, P044
O3
P050
P099
P025
P018
P001
O1
P008
P115
P118
P002, P124
P002, P124
P049
O5
P016, P033
O8, P087, P091
P092
P109
H.
Hadzi-Djokic J.
Hafeez S.
Halawa GonzГЎlez O.B.
Halgunset J.
Hallemeier C.L.
Hammers H.
Hampel C.
Hannaoui Hadi N.
Hansen V.N.
Harmenberg U.
Haroon N.
Harris V.
Harza M.
Hawrylewicz L.
Hayat H.
Haz M.
Heath E.I.
Heerschap A.
Heidenreich A.
Hellborg H.
Helou J.
Hennenlotter J.
Hermieu J.F.
Hiller K.
Hirmand M.
Hjälm-Eriksson M.
Hodge L.
Hong J.
P022
P013, P014
P034, P038
P092
P125
P036, P112, P115
O11
P008, P041, P044
P014
P104
P029
P014
O4
P067
P036
P001
P114
O6
O10
P104
P107
P097
P083
O11
O10
P104
P040
P048
185
Indices
Fernandez P.L.
FernГЎndez J.M.
FernГЎndez-Serra A.
Ferrer F.
Ferrer Da Pena M.D.
Feyerabend S.
Figueroa A.
Figurin K.M.
Filianoti A.
Filonenko E.V.
Fiori C.
Fiorino C.
Fitzpatrick J.
Fizazi K.
Fleischmann A.
Fonteyne V.
Fossion L.M.C.L.
Fraga A.
Frances A.
Frank G.A.
Fumado L.
Fumero Gorrin C.
Hoogeman M.
Huddart R.A.
Hughes P.F.
Huguet J.
Hupertan V.
Hussain M.
Hutson T.E.
Huynh H.
P074
P013, P014
O7
P026, P028, P126
P083
P115
O4, P040
P030
I.
Iacovelli R.
O5
Iavarone F.
O3
Ingelmo C.
P006
Instituto De InvestigaciГіn BiomГ©dica
De Salamanca. P033
Isa N.
P076, P108
Ish-Shalom M.
P036, P112
Indices
J.
JaГ©n J.
P076, P108
Jagar P.
P049
Jalil R.
P055, P100, P101,
P103
James N.D.
P117
Jansen E.
O1
Jereczek-Fossa B.A.
P070
Jespersen C.
O9
Jinga V.
O4
Jocham D.
O11
Johnson M.
P012
Jolivet S.
P058
Jones K.
P014
Jonstam G.
P104
Jung H.
P048
K.
Kallen K.
Kalpinskiy A.S.
Kaprin A.D.
Karazanashvili G.
Keizman D.
Keshishev N.G.
Khametov R.Z.
Khoo V.
Kimov K.A.V.
Kirkels W.
Klimov A.
Klotz L.
Koedooder C.
Kojic A.
Koldewijn E.L.
Kolkman-Deurloo I.K.
186
O11
P045, P046
P090
P116
P036, P112
P060, P061, P080
P065
P014
P037
P074
P039
P109
O1
P098
P064
P074
Koning C.C.E.
Korobkin A.S.
Kovchenko G.V.
Kovel S.
Krasheninnikov A.A.
Kraus O.
Krupinov G.E.
Kruslin B.
Kulik R.
KГјbler H.
Kumar V.
Kurt K.
O1
P054
P061
P036, P112
P056, P075
P057
P084
P057
P067
O11
P011
O11
L.
Lad T.E.
Lafuente De Carvalho J.M.
Lalondrelle S.
Lamb B.
Lambert B.
Lander T.
Lanocita R.
Larner T.
Lee J.H.
Lee S.Y.
Lefkopoulos D.
Leibovich B.C.
LeitГЈo T.
Levens W.
Li C.
Lin J.
Lipatov O.
Liu G.
Lo Re G.
Locatelli C.
Loewy J.
Longo G.
Lopes T.
LГіpez J.M.
LГіpez Cubillana P.
LГіpez GonzГЎlez P.
LГіpez Guerra J.L.
LГіpez-Guerrero J.A.
Lorente J.A.
Lorenzo-GГіmez M.F.
Lorusso V.
Louro N.R.
Lozano J.J.
Lucet J.C.
Luciani L.G.
Lumen L.
Lundon D.
Lyulko O.
P049
P123
P014
P100, P101
O12
O11
P002
O7
P048
P115
P107
P125
P050
P120
P104
P114
O4
P114
P118
P071
P040
P071
P050
P005
P059
P059
P076, P108
P051
P053, P086
P016, P033
O5
P123
P032
P058
P043
O12
P094
O4
N.
Nadeem M.
P024
Nair R.
Nana N.O.
Nanlohy-Manuhutu E.L.
Nash M.
Ndjavera W.
Necchi A.
Neumann A.
Nicolai N.
Nikolic Z.
Nilsson S.
NistГ©r M.
Nohales G.
NГёrgaard M.
Nosov D.
Nunes A.
Nyushko K.M.
O7
P093
P120
P095
P011
P002, P124
P036, P112
P002, P066, P068,
P085, P124
P098
P104
P104
P086
O9
O4, P040
P050
P023, P045, P046,
P056, P075, P119
O.
Obuhov A.A.
Ochoa C.
Oh W.K.
Ohlmann C.H.
Olarte BarragГЎn E.
Olesen T.K.
O’neil J.
O’neill A.
Ortega C.
Ost P.
OsГіrio L.
P084
P018, P025
P114
P110
P059
P109
P055
P094
O5, P047
O12
P035
P.
Padilla-FernГЎndez B.
Palou J.
Paolini B.
Pappagallo G.
Parada R.
Park J.
Parma P.
Parmiani G.
Patel N.
Patil S.
Pawitan Y.
Payne H.
Peer A.
Pejcic T.
Pelkman M.
Peng Z.
Pennati M.
Pereira S.
Peri L.
P016, P033
P005, P018, P025
P066, P124
P118
P018, P025
P048
P043
O11
P055
P049
P104
P109
P036, P112
P022
P021
P104
P002
P050
P026, P028
187
Indices
M.
Magnani T.
P066, P068, P085,
P089
Maimon N.
P036, P112
Malet Munte A.
P008
Malossini G.
P043
Manea C.N.
P079
Marenghi C.
P066, P068, P085
Mari C.
P069
Mariani L.
P002
Marsiglia H.
P076, P108
Martin-Rodriguez A.
P016, P033
Martinho D.
P050
Martini T.
P118
Martinotti A.S.
P070, P071
Martins L.
P035
Martos Calvo R.
P008, P041, P044
Masini C.
O5
Massari F.
O5
Matute R.
P076, P108
Matveev V.B.
P015, P031, P037,
P039
Maurer T.
O11
Mauro F.A.
O8, P087
Maynard D.
O2
Mcdonald F.
P014
Mengual L.
P006, P032
Mercade Carceller A.M.
P006
Messina C.
O5
Messina F.
P069
Michaelson D.
P115
Michielsen D.
P052
Milella M.
O5
Miller K.
O10
Miron-Canelo J.A.
P033
Molina A.
P026
Monllor Gisbert J.
P034, P038
Moran S.
P114, P115
Moreno AlarcГіn C.
P059
Moreno AvilГ©s J.
P059
Morlino S.
P087, P095
Morosi C.
P002
Mortimer P.
P114, P115
Mosca A.
O5
Motzer R.
O4, P040
Mulders P.
O10
MuГ±oz Rodriguez J.
P008, P041, P044
Muraglia A.
P091
Mussari S.
P106
Indices
Perin A.
P118
Persson B.
P109
Peters M.V.
P031
Petrylak D.
P114
PhD Programme in Urologic Oncology,
Catholic University
O3
Pieters B.R.
O1
Pignoli E.
O8, P095
Pili R.
P036, P112
Pilla L.
O11
Pinnaduwage D.
P095
Pino L.
P053, P086
Pinto F.
P009
PinzГіn Navarrete C.
P059
Pisansky T.M.
P125
Polotskiy B.E.
P039
Polyakov V.A.
P045, P046
Polyakovsky K.A.
P007
Porpiglia F.
P043
Portero Navarro J.
P034
Potoldykova N.V.
P007
Praag J.
P074
Pramana S.
P104
Prati V.
P047
Prats Lopez J.
P008, P041
Prencipe M.
P094
Prera Vilaseca A.
P008, P041, P044
Prieto GonzГЎlez A.
P059
Primi F.
O5
Procopio G.
O5
Puebla F.
P076, P108
Pugliese D.
P009
Puxeu J.
P111
Q.
Quispe K.
P111
R.
Racioppi M.
Rafiq M.
Ragazzi E.
Raggi D.
RamГ­rez-Backhaus M.
Rancati T.
Ravery V.
Reindl M.
Ribal M.J.
Rijo E.
Rivin Del Campo E.
Roach M.
P009
P011
O3
P002, P124
P051
O8, P066, P068,
P085, P087, P091
P058, P083
O11
P006, P026, P028,
P032, P126
P053, P086
P076, P108
P095
188
Robson L.
Rocha A.
Rodriguez A.
Rodriguez A.
Rodriguez Faba O.
Rodriguez Talavera J.
Romac S.
Romanov V.A.
Rosenbaum E.
Rotzer D.
Ruatta F.
Rubio-Briones J.
Russo L.M.
Russo M.
Ryan C.J.
P012
P035
P107
P053
P005, P018, P025
P038
P098
P015
P099, P112
P003, P004
P047
P051
P106, P118
P076, P108
P115
S.
Saad F.
Sacco C.
Sacco E.
Ећahin A.F.
Salvioni R.
Sanchez-Reyes A.
Sandul A.
Santoni M.
Satariano N.
Sava T.
Savic Pavicevic D.
Scalchi P.
Schalken J.A.
Schilling D.
Schostak M.
Schultze-Seemann W.
Seiler R.
Sella A.
Selnaes K.M.
Semin A.V.
Sevdalis N.
Severin S.E.
Shaplygin L.V.
Shariya M.A.
Shevchenko V.E.
Shin D.B.
Shore N.
Silva D.
Silva J.D.
Silva R.
Silva-Ramos M.
Silva-AbuГ­n J.M.
Sim Y.
Singh A.
O10
O5, P118
O3, P009
P121
P002, P066, P068,
P085, P089, P124
P076, P108
P050
O5
P069
P118
P098
P069
P006, P032
P097
O11
O11
P003, P004
P036, P112
O6, P092
P090
P100, P101, P103
P060
P065
P054
P031
P048
P109
P035
P035
P050
P035
P016, P033
P030
P049
P036, P112
P060, P061, P080
P057
P104
O4
P011
P012
P065
P051
O11
P057
P020
P073, P088
P066, P068, P124
O11
O11, P097
O4, O10
P057
O4
P048
P067
O4
T.
Tammela T.L.J.
Taplin M.
Taylor H.
Tessem M.B.
Thalmann G.N.
Thompson A.
Thorpe A.
Thottakam B.M.V.
Tiscione D.
Tomas D.
Tomatis S.
Tombal B.
Tomczak P.
Tomovic S.
Tortoreto F.
Trnski D.
Trojan L.
Tschui J.
Tunn U.W.
TГјrkeri L.
Turkin I.N.
P109
O10
P014
O6, P092
P003, P004
P014
P012
O2
P043
P057
O8, P087, P095
P109
O4
P098
O8
P057
O11
P003
P110
P121
P039
U.
Ubre A.
UrbaЕ„czyk H.A.
P053, P086
P067
V.
Valdagni R.
O8, P066, P068,
P085, P087, P089,
P091, P095
Valduga F.
O5
Valery V.E.P.P.
P064
Van Aarle S.
P020, P120, P122
Van De Kar M.
O1
Van Der Heijden A.G.
P006, P021, P032
Van Dooren V.P.M.
P020, P120, P122
Van Erps P.
P073, P088
Van Gils F.
P078
Van Os R.M.
O1
Van Rooij P.
P074
Vassella E.
P003
Vattovani V.
P043
Vavassori A.
P070
Vavassori V.
O8, P087, P091
Veccia A.
P106, P118
Verhoeven R.H.A.
P064
Verstraet R.
P107
Vicente E.
P041
Vicente Palacio E.
P008, P044
Villa S.
P066, P068, P085,
P089, P091
Villavicencio H.
P005, P018, P025
Villeirs G.
O12
Vinarov A.Z.
P007, P054
Virseda-RodrГ­guez A.J.
P016
Viset T.
P092
Vite C.
P070, P071
Vizoso F.
P005
Volkova M.I.
P015, P031, P037,
P039
Vom Dorp F.
O11
Vorobyev N.
P045, P046, P056,
P075, P119
Voskanyan G.A.
P054
Vozdvizhenskiy M.O.
P065
Vukotic V.
P098
Vukovic I.
P098
Vuye P.
O12
W.
Wade R.J.
Warren-Oseni K.
Watson W.
Wedel S.
Wilson A.
Wilson P.
Wingmo I.
Witjes J.A.
P011
P014
P094
O11
O2
O2
P104
P006, P021, P032
189
Indices
Sinibaldi V.
Sivkov A.V.
Skerk V.
Skoog L.
Slichenmyer W.
Small M.
Smith H.E.
Solovov V.A.
Solsona E.
Sommerauer M.
Sonicki Z.
Sonneveld A.
Sorber M.
Stagni S.
Steiner U.
Stenzl A.
Sternberg C.N.
Stimac G.
Strahs A.
Sym S.J.
Szczepanik K.
Szczylik C.
P109
P025
O6, P092
Y.
Yin W.
Yoon S.J.
Yuen J.
P040
P048
P030
Z.
Zaffaroni N.
Zardoya E.
Zerini D.
Zhang J.
Zustovich F.
P002
P111
P070
O4
P118
Indices
Wolff J.M.
Wong A.
Wright A.
190
191
Indices
Abstracts sorted by Topic
Bladder Cancer
Clinical/Basic research:
P001, P002, P003, P004, P005, P006
Diagnosis/Staging:
O2, P007, P008
Treatment:
O1, P009, P011, P012, P013, P014, P015, P016, P018, P020, P021, P022, P023
Prognosis:
P024, P025, P026, P028
Follow up:
P029
Renal Cell Carcinoma
Clinical/Basic research:
O3, P030, P031, P032, P033
Diagnosis/Staging:
P034, P035
Treatment:
O4, O5, P036, P037, P038, P039, P040, P041, P042, P043, P044, P045, P046, P047
Prognosis:
P048
Localized Prostate Cancer
Prevention:
P049
Diagnosis/Staging:
O6, P050, P051, P052, P053, P054, P055, P056, P057, P058, P059, P060, P061
Treatment:
O7, P064, P065, P066, P067, P068, P069, P070, P071, P073, P074, P075, P076, P078, P079, P080
Prognosis:
P083
Indices
Follow Up:
P084
Quality of life:
O8, P085, P086, P087, P088, P089, P090, P091
192
Prostate Cancer
Research:
O9, P092, P093, P094, P095
Basic:
P097, P098, P099, P100, P101
Basic/Translational:
P103, P104
Clinical:
O10, P106, P107, P108
Advanced Prostate Cancer
Treatment:
O11, O12, P109, P110, P111, P112, P114, P115, P116, P117, P118, P119
Prognosis:
P120, P121
Follow up:
P122
Testicular Cancer
Diagnosis:
P123
Treatment:
P124, P125
Indices
Penile Cancer
P126
193
Faculty List
Indices
A. Alcaraz, Barcelona (ES)
F. Algaba, Barcelona (ES)
W. Artibani, Verona (IT)
J. Barentsz, Nijmegen (NL)
J. Bellmunt, Barcelona (ES)
D. Berthold, Lausanne (CH)
A. Bossi, Villejuif (FR)
M. Brausi, Modena (IT)
A. Briganti, Milan (IT)
J. Catto, Sheffield (GB)
N. Clarke, Bradford (GB)
S. Culine, Paris (FR)
D. Dearnaley, Sutton (GB)
J. De Bono, Sutton (GB)
G. De Meerleer, Ghent (BE)
M. De Santis, Vienna (AT)
N. Desouza, Sutton (GB)
T. Eisen, Cambridge (GB)
K. Fizazi, Villejuif (FR)
S. Fossa, Oslo (NO)
J. FГјtterer, Nijmegen (NL)
D. Hollywood, Dublin (IE)
S. Horenblas, Amsterdam (NL)
N. James, Birmingham (GB)
194
S. Joniau, Leuven (BE)
R. Karnes, Rochester (US)
V. Khoo, London (GB)
F. Lecouvet, Brussels (BE)
M. Mason, Cardiff (GB)
A. Morganti, Rome (IT)
N. Mottet, Saint Etienne (FR)
P. Mulders, Nijmegen (NL)
S. Osanto, Leiden (NL)
A. Padhani, Northwood (GB)
J. Palou, Barcelona (ES)
C. Parker, Sutton (GB)
T. Powles, London (GB)
M. Rubin, New York (US)
M. Spahn, Bern (CH)
A. Stenzl, TГјbingen (DE)
C. Sternberg, Rome (IT)
B. Tombal, Brussels (BE)
L. TГјrkeri, Istanbul (TR)
N. Van As, London (GB)
H. Van Poppel, Leuven (BE)
M. Van Vulpen, Zeist (NL)
G. Villeirs, Ghent (BE)
www.emucbarcelona2012.org
4th EMUC, Barcelona, November 2012
Embracing Excellence
in Prostate, Bladder
and Kidney Cancer
16-18 November 2012
Barcelona, Spain
Programme/
Abstract book
These are the challenges we have set ourselves because Changing tomorrow is more than just
words – it is what we must do to give cancer patients real hope of a tomorrow worth looking
forward to.
www.astellas.eu
В© September 2012 Astellas Pharma Europe Ltd. CSC0461
ASTELLAS, Leading Light for Life, the Star logo, Changing tomorrow and the
Ribbon logos are trade marks of Astellas Pharma Inc. and/or its related entities.
Programme/Abstract book
Astellas has made a commitment to change
tomorrow – a commitment that we are bringing to the
field of oncology. We aim to create innovative treatments that will
genuinely improve the lives of cancer patients. To do this we are focusing
our R&D and partnership efforts into precision medicine that will create first-in-class
or best-in-class programmes. This has resulted in no fewer than 12 separate therapies under clinical
development into conditions including prostate cancer, other solid tumours like pancreatic cancer,
breast cancer and advanced renal cell carcinoma, as well as haematological malignancies.
4th European Multidisciplinary Meeting on Urological Cancers organised by:

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