Tap for Burn-Out Flier - Sweet Home Sweet Ride

Patient & Physician in Co-Partnership
New Developments in Prostate Cancer Treatment
NOVEMBER 2010 VOL 13: NO 4
By: Jim O’Hara – PCRI Educational Facilitator
PCRI wishes to say a “BIG THANK YOU” to all
of the attendees (over 750 from 38 states and
8 countries), speakers, supporters, volunteers,
production crew and the Marriott LAX for
making the 2010 Prostate Cancer Conference
a tremendous success. Many long-time
attendees commented it was the “BEST EVER”.
2 From the Editor
3 Understanding and Applying Risk
Assessment for Prostate Cancer
By Matthew R. Cooperberg, MD, MPH
The clues to your personal prostate cancer risk are
hidden in your Medical Record. Dr. Cooperberg is one
of the most published authors on prostate cancer and
has been a leader in the development of the CAPRA
prostate cancer risk scoring system developed at U.C.
San Francisco.
8 MRI for Prostate Cancer: Information for
Patients and Families
By Daniel Margolis, MD.
Latest MRI technology provides the highest resolution
images of cancer in and around the prostate.
14 Targeted Biopsies and Active Surveillance
By David Agus, MD.
Is it safe to avoid the side-effects of prostate cancer
therapy? Risk assessment helps identify who is a
candidate for active surveillance.
18 TIP: Testosterone Inactivating
By Mark Scholz, MD.
On Saturday, the conference was moderated
by Dr. Mark Moyad. We had the usual lineup
of excellent speakers, who presented cuttingedge information dealing with all stages of
(Continued on page 24)
prostate cancer.
24 Best of
The 2010
Prostate Cancer
By Jim O’Hara
Highlights from the presentations.
30 PCRI Presents Harry Pinchot and Catalyst
The Editor
The PCRI believes most men
should be screened for prostate
cancer. But, if PC is found, many
men at low risk might safely
delay treatment; possibly for
life. This Insights issue reports on a better risk assessment
tool, better MRI imaging, and millimeter accuracy
targeted biopsies that give men and their doctors better
information to use when deciding on therapy options.
Why Is The Roosevelt Hotel Painted Blue?
Blue September – Changing the face of Prostate Cancer in America
hen you think of the color
blue, prostate cancer probably isn’t the first thing that springs
to mind. But this year The Prostate
Cancer Research Institute (PCRI)
teamed together with Blue September, a prostate cancer awareness and
fund-raising campaign, to help make
that change, and begin to level the
playing field to give prostate cancer
the profile it deserves.
There is no doubt that when it comes to breast cancer, the pink
initiative has been a huge success. Not as well known, is that every year
in America, more men are diagnosed with prostate cancer than women
with breast cancer. But prostate cancer gets nowhere near the same
fanfare and public sympathy. — That is, until now!
In 2010, the inaugural year of the campaign, the PCRI and Blue
September have made huge inroads, getting the word out about
prostate cancer and the need for men to be more aware of the disease
and get a checkup, by spreading the spirit of blue all over town.
Buildings, landmarks, familiar brands and icons, and most importantly,
faces, were turned blue, encouraging everyone to �face up’ and get
proactive about prostate cancer.
(Continued on page 29)
PCRI Insights • www.PCRI.org
Editor : Nathan Roundy
Review Board: Duke K. Bahn, MD
Stanley A. Brosman, MD
Arthur N. Lurvey, MD
Mark C. Scholz, MD
Michael Steinberg, MD
Graphic Designer John I. Blanda
Prostate Cancer Research Institute
5777 W. Century Boulevard, Suite 800
Los Angeles, CA 90045
Phone (310) 743-2116 | Fax (310) 743-2113
Helpline (310) 743-2110 | E-mail: [email protected]
www.pcri.org and www.prostate-cancer.org
Board of Directors
Chester A. Swenson, President
Chairman, Marketing & Financial
Services Enterprises
Jerome Seliger, PhD, Vice President
Professor of Health Administration,
California State University, Northridge
Barry L. Friedman, JD, Secretary
Attorney at Law
T. Kent Graham, Treasurer
Financial Consultant, T. Kent Graham &
Duke K. Bahn, MD
Director, Prostate Institute of America
Stanley A. Brosman, MD
Pacific Urology Institute, Pacific
Clinical Research
Arthur N. Lurvey, MD
Medicare Contractor Medical Director
Jerry Peters
MCG Records
Claudia B. Sangster, Esq.
Director of Philanthropy, Estate & Trust
Services, Harris myCFO, Inc.
Mark C. Scholz, MD, PCRI Co-founder
Director, Prostate Oncology Specialists
Michael Steinberg, M.D., FAC
Professor and Chair, Department of
Radiation Oncology, David Geffen
School of Medicine at UCLA
The cost of printing and mailing this newsletter
is made possible through a generous grant from
The Life Extension Foundation
P.O. Box 229120, Hollywood, FL 33022
800-544-4440 www.lef.org/prostate
В© 2010 Prostate Cancer Research
Institute. All Rights Reserved
PCRI Insights, November 2010, Vol 13: No 4
Understanding and
Applying Risk Assessment
for Prostate Cancer
Matthew R. Cooperberg, MD, MPH
Introduction: The Heterogeneity of Prostate Cancer
ith over 200,000 new diagnosis every year, prostate cancer is by a wide measure the
most common cancer among men in the
United States. Over 30,000 men will die
of the disease this year.1 This number is
surpassed only by lung cancer among
cancers affecting men in this country, yet
is clearly dwarfed by the number of diagnoses. These numbers summarize the
challenge of prostate cancer: screening
programs based on measurement of prostate specific antigen (PSA) levels among
otherwise healthy men are intended to
identify and offer early curative treatment
to the men at risk of dying of prostate
caner — and indeed, since PSA screening
started in earnest in the early 1990s, prostate cancer mortality rates at the population level have fallen about 40%.1 But in
the course of identifying the potentially
lethal prostate cancers, many more tumors are found that are indolent, i.e., that
would never cause symptoms or reduced
lifespan if they were never detected.
Most men with prostate cancer in fact die
of heart disease — just like men who have
not been diagnosed with prostate cancer.
The side effects and costs of over-treating
these low-risk prostate tumors amount to
one of the most substantial public health
problems related to the disease.
The obvious solution is to treat only
those prostate cancers that are likely to
cause problems and ignore the rest. In
fact, the last several years have seen significant progress toward this paradigm
of selective and risk-adapted treatment.
Men with low-risk prostate cancer —
tumors unlikely to progress — are now
offered active surveillance: careful monitoring of the tumor with serial PSA tests
and repeat prostate biopsies. With large
cohorts of hundreds of men now reported
from major centers across North America,
this strategy is increasingly accepted as
safe and effective: for the large majority
of men with low-risk tumors, the window
of opportunity for cure lasts for years, so
treatment after a period of surveillance
(e.g., if the PSA is rising consistently) is
as likely to cure as immediate treatment.
In the interim, the risks and side effects
of surgery, radiation therapy, hormonal
therapy, etc. may be avoided.2 Men with
intermediate-risk cancer generally should
receive surgery or radiation therapy, and
those with higher-risk prostate cancer
often need combination therapy — either
surgery followed by radiation or radiation together with hormonal therapy.
(Continued on page 4)
“Since the
early 1990s,
rates at the
level have
fallen about
“For men
with low-risk
tumors ...
after a period
of surveillance
is as likely
to cure as
www.PCRI.org • PCRI Insights
The Key Players: PSA, Gleason Grade, and Tumor Extent
Risk-stratifying prostate cancer — determining which
are at low-, intermediate-, or high-risk—is thus absolutely critical to effective treatment. How exactly to
use risk stratification in practice is at once simple and
complex. The simple part is what factors to consider,
as there is broad agreement on the key determinants of
prostate cancer risk. First is the blood level of PSA.
For all the controversy surrounding PSA testing for
prostate cancer screening, the test is quite reliable in
predicting outcomes among men who have already
been diagnosed with cancer. Except in rare cases, the
lower the PSA, the lower the cancer risk. PSA levels under 10 are usually considered low-risk, but even
within the <10 category, lower is better. When the
PSA is over 20 at time of diagnosis, there may be detectable cancer outside the prostate, so imaging tests
such as bone scans are ordered to rule out metastatic
The second key risk factor is the Gleason grade,
which is a measure of the aggressiveness of the cancer
cells as determined by the pathologist examining
prostate tissue (e.g., from a biopsy) under the
microscope. The Gleason grade is assigned on a 1 to 5
scale, but in contemporary practice grades 1 and 2 are
rarely seen, so for practical purposes, Gleason grade
3 indicates low-grade cancer, Gleason 4 indicates
intermediate-grade, and Gleason 5 indicates highgrade. Prostate cancer can be heterogeneous even
within an individual prostate, so the Gleason score
is expressed as two numbers: the first number is the
primary pattern—i.e, the most common pattern—and
the second number is the secondary pattern.
The two numbers are sometimes added for a
final score, but are better expressed as a primary +
secondary score. A Gleason 3+3 (or Gleason 6) tumor,
for example, is uniformly low-grade. A Gleason 3+4
tumor is mostly low grade with some intermediategrade, whereas a Gleason 5+4 tumor is mostly highgrade with some intermediate-grade. In terms of grade,
the major driver of prostate cancer risk is the primary
pattern. Thus Gleason 4+3 tumors are significantly
more aggressive than Gleason 3+4 tumors—which is
why lumping all such cases as “Gleason 7” is not ideal.
The PSA and Gleason score are the most important
risk parameters in most cases. The third is some
PCRI Insights • www.PCRI.org
measure of tumor extent—how much cancer there is
and where it is. There are different ways to articulate
extent. The most common is tumor clinical stage,
and is expressed with three letters: T, N, and M. A
tumor which is not palpable on rectal exam or visible
on imaging tests (e.g., ultrasound) is designated
T1, one which is palpable or visible but is confined
to the prostate is T2 (with subtypes T2a, 2b, and 2c
depending on how large the palpable tumor is), and
one which is felt or seen to extend beyond the edge of
the prostate is T3. If there are involved lymph nodes,
the cancer is N1, and if there are metastases in the
bones or elsewhere, it is M1. Metastatic (i.e., N1 or
M1) cancer is very uncommon at diagnosis in the era
of PSA screening, and the large majority of tumors
are stage T1 or T2.
The problem is that neither rectal exams nor imaging
tests are particularly accurate in identifying tumors
which are confined to the prostate, and as a result
clinical stage offers little information when considered
in context of other variables such as PSA and Gleason
grade for tumors which are confined to the prostate.3 A
more accurate measure of tumor extent is to quantify
how much cancer is seen on biopsy. This can be
measured as the number or percent of biopsy cores
positive—for example, if a 12-core prostate biopsy is
performed and 10 cores are involved with cancer, the
volume of cancer is greater than if only 2 cores are
involved. Some pathologists will also report the extent
of cancer involvement within each needle core.
Putting It All Together
Once the PSA, Gleason score, and tumor extent is
determined, the question becomes how to integrate
this information to give an overall sense of cancer
risk. This question is more complicated than identifying the variables: by one count there are over 100
formulae, calculators, nomograms, and other instruments intended to determine risk at various prostate
cancer decision points.4 Most are based on PSA,
Gleason, and clinical stage and/or some measure of
biopsy core involvement; some add other parameters
such as patient age, year of diagnosis, or prostate size
(which can impact interpretation of the PSA).
One of the first widely-adopted approaches to
risk stratification is a 3-level risk group classification
published by Anthony D’Amico and colleagues at
Harvard University5 and formally adopted by the
American Urological Association’s practice guideline
for localized prostate cancer treatment.6 In this
classification, men are assigned to one of three groups
as follows:
Figure 1: Kattan Nomogram
Low-risk: PSA ≤10, Gleason ≤6, and
clinical stage T1 or T2a Intermediate-risk: PSA 10-20, Gleason 7,
or clinical stage T2b
High-risk: PSA >20, Gleason 8-10, or
clinical stage T2c or T3a
The major advantage to this system is its simplicity,
and it is used very commonly. However, it has significant
drawbacks. First, it over-weights T stage which, as noted
above, is not a very accurate measure of tumor extent
within the T2 category. Second, it does not distinguish
between Gleason 3+4 and 4+3 tumors which (again, as
noted above) behave very differently within the Gleason
7 category. Finally, and most importantly, it does not
combine information from the risk variables. A PSA
18, Gleason 4+3, stage T2b tumor and a PSA 4, Gleason
3+4, stage T1c tumor are both “intermediate-risk” in this
classification, but would be expected to behave quite
Multivariable models combine PSA, Gleason grade,
and other parameters, integrating information from each
to give a more accurate overall impression of risk. There
are many such models, and though the math underlying
them tends to be similar, there are several different
ways to present the data. For example, Alan Partin and
colleagues at Johns Hopkins University published a set
of lookup tables to predict outcomes after surgery such
as extra-prostatic extension of tumor.7 The tables simply
list likelihoods for the outcome of interest for men with a
given set of risk factors (again, PSA, Gleason score, and
T stage), and are used as a reference.
Nomograms are another popular way of presenting
information from multivariable risk models. Popularized
by Michael Kattan and Andrew Stephenson and colleagues
at Memorial-Sloan Kettering and the Cleveland Clinic,
nomograms are graphs on which a patient is assigned
a set number of points for each variable of interest; the
points are then summed to predict the outcome of interest,
which is given with a В±10% margin of error.
For example, using the original nomogram
published by Kattan,8 which predicts likelihood of
remaining free of recurrence 5 years after surgery,
the patient mentioned above with PSA 4, Gleason
3+4, stage T1c disease would receive 84 points (37
+ 47 + 0) corresponding to a roughly 84% В±10%
likelihood of recurrence-free survival. The patient
with PSA 19, Gleason 4+3, stage T2b would receive
155 points (74+50+31), indicating a 25% В±10%
likelihood of recurrence-free survival. An updated
version incorporates data on the number of biopsy
cores involved with cancer.9
Many other nomograms have been published since,
intended to predict pathologic outcomes (similar to
the Partin tables), biochemical outcomes after surgery
or radiation therapy, or longer-term outcomes like
metastasis or mortality.4 Two important caveats should
be noted. First, a given nomogram is developed
based on data from a specific cohort of men, usually
treated in one or a few academic centers in which a
small number of highly-trained surgeons or radiation
oncologists treat large volumes of patients. A great
deal of caution must be exercised in calculating
specific risks of recurrence for patients treated in
other settings by different clinicians, and ideally
nomograms should be formally validated in a given
setting before they are used routinely in that setting.
Second, with computer software it is very easy to
calculate multiple nomogram scores simultaneously,
creating a temptation to use the nomogram scores to
compare treatment options such as surgery or radiation.
Nomograms cannot be used this way—the cohorts of
patients used to develop each are very different, as are
the definitions of the outcomes reported. In particular,
with few exceptions nomograms predict likelihood of
PSA recurrence after treatment, (Continued on page 6)
www.PCRI.org • PCRI Insights
cohorts—our group at the University of California,
San Francisco developed the UCSF Cancer of the
Prostate Risk Assessment (CAPRA) score, which
is intended to combine the accuracy of nomograms
with the ease of calculation of the a risk grouping
system.10 To calculate the CAPRA score, points are
assigned based primarily on the PSA and Gleason
score, with lesser weights given to T-stage, percent
of biopsy cores positive, and patient age:
Figure 2: CAPRA Score
Matthew R. Cooperberg, MD, MPH
Matthew R. Cooperberg earned MD and MPH
degrees concurrently from Yale University in
2000. He completed his General Surgery and
Urology training, and a fellowship in Urologic
Oncology, at the University of California San
Francisco, where he subsequently joined the
faculty. He has written over 70 peer-reviewed
scientific articles. He lives in San Francisco
with his wife and son.
which is defined very differently after radiation than after
surgery. Thus nomograms may be useful to give a patient
undergoing a specific treatment a sense of the likely
outcomes, but cannot help guide treatment decisions.
The CAPRA Score
Because of these limitations—and the fact that
nomograms are difficult to calculate for hundreds or
thousands of patients in research settings and cannot
be used to consistently identify low- or high-risk
PCRI Insights • www.PCRI.org
Points are added to yield a 0-10 score. Overall,
every 2-point increase in score (e.g., from 2 to 4 or
from 5 to 7) indicates roughly a doubling of risk.
CAPRA scores in the 0-2 range indicate relatively lowrisk disease, CAPRA 3-5 tumors are intermediate-risk
and CAPRA 6-10 tumors are high-risk. Assuming
they were over 50, with clinical stage T1 or T2 and
<33% of biopsy cores positive, the two hypothetical
patients described above would have CAPRA scores
of 2 and 6, placing them in the low- and high-risk
groups, respectively.
The CAPRA score was developed based on data
from men in the Cancer of the Prostate Strategic
Urologic Research Endeavor (CaPSURE) registry,
which includes men treated at dozens of clinical sites,
mostly community-based, across the U.S.. It has also
been validated in a large academic center cohort,11 and
in multi-center cohorts of men in the Veterans Affairs
system12 and in Europe.13 It was recently found to
offer better accuracy than competing instruments in
an independent head-to-head comparison based on
another European cohort.14 Moreover, it has been
shown to predict metastasis and mortality as well
as biochemical outcomes—after surgery, radiation
therapy, and hormonal therapy.15
The CAPRA score can be
determined without a complex table
or software, and with a little practice
can be calculated from memory.
Moreover, it is easy to calculate
for many patients at once and has
been validated in multiple settings
using the same definitions of low, intermediate-, and high-risk, so is
ideally suited for the research setting
as well as for clinical practice. It is
important to note that the CAPRA
score is primarily meant to indicate
relative rather than absolute risk.
Thus a tumor with a CAPRA score
of 4 has an intermediate-risk of
recurrence or progression after
surgery or radiation. This tumor
will be more likely to progress than
one with a score of 2, and less likely
than one with a score of 6, regardless
of treatment approach or setting.
The specific risk (e.g., likelihood
of being free of disease at 5 years
after treatment), while roughly
consistent across different cohorts,
will depend at least in part on factors
such as surgeon skill and experience,
pathology grading practices, etc.
Conclusion: Risk Assessment
In Practice
Data from the best available
studies reported to date leave
little question that prostate cancer
screening saves lives.16 However,
there is also no question than many
men are harmed by over-treatment
resulting in such screening efforts.
High-quality treatment for prostate
cancer entails some determination
of overall risk, using the D’Amico
classification at a minimum, but
preferably using a multivariable
tool such as a nomogram or the
CAPRA score. Treatment in turn
should be guided by cancer risk and
an individual man’s overall health
and life expectancy (not necessarily
by his chronological age). Though
some trends are slowly improving,
there is still too much variation
in prostate cancer care, too much
over-treatment of low-risk disease,
and frequent under-treatment of
high-risk disease.17
It is important to remember that
even high-risk prostate cancer is
slow to progress compared to lung,
pancreas, and other aggressive malignancies. So there is almost always
ample time to seek multiple treatment options and to make a carefully
considered decision. Lower risk
prostate cancers grow so slowly that
some thought leaders are starting
question whether they should even
be called “cancer” at all,18 given the
substantial psychological impact of
the word itself. Consistent use of
risk stratification tools will ameliorate both over-and under-treatment,
will save millions of dollars in needless health care expenditures, and ultimately will improve both survival
and quality of life for the hundreds
of thousands of men diagnosed each
year in the U.S. and worldwide.
1. Jemal A, Siegel R, Xu J, Ward E. Cancer
Statistics, 2010. CA Cancer J Clin. 2010.
2. Dall’Era MA, Cooperberg MR, Chan JM, et al.
Active surveillance for early-stage prostate
cancer: review of the current literature. Cancer.
3. Reese AC, Cooperberg MR, Carroll PR.
Minimal impact of clinical stage on prostate
cancer prognosis among contemporary
patients with clinically localized disease. J Urol.
4. hariat SF, Karakiewicz PI, Roehrborn CG, Kattan
MW. An updated catalog of prostate cancer
predictive tools. Cancer. 2008;113(11):30753099.
5. D’Amico AV, Whittington R, Malkowicz SB, et al.
Biochemical outcome after radical prostatectomy,
external beam radiation therapy, or interstitial
radiation therapy for clinically localized prostate
cancer. JAMA. 1998;280(11):969-974.
6. Thompson I, Thrasher JB, Aus G, et al.
Guideline for the management of clinically
localized prostate cancer: 2007 update. J Urol.
7. Partin AW, Kattan MW, Subong EN, et al.
Combination of prostate-specific antigen,
clinical stage, and Gleason score to predict
pathological stage of localized prostate
cancer. A multi-institutional update. JAMA.
8. Kattan MW, Eastham JA, Stapleton AM,
Wheeler TM, Scardino PT. A preoperative
nomogram for disease recurrence following
radical prostatectomy for prostate cancer. J
Natl Cancer Inst. 1998;90(10):766-771.
9. Stephenson AJ, Scardino PT, Eastham JA, et
al. Preoperative nomogram predicting the 10year probability of prostate cancer recurrence
after radical prostatectomy. J Natl Cancer Inst.
10. Cooperberg MR, Pasta DJ, Elkin EP, et al.
The University of California, San Francisco
Cancer of the Prostate Risk Assessment score:
a straightforward and reliable preoperative
predictor of disease recurrence after radical
prostatectomy. J Urol. 2005;173(6):1938-1942.
11. Zhao KH, Hernandez DJ, Han M, Humphreys
EB, Mangold LA, Partin AW. External validation
of University of California, San Francisco,
Cancer of the Prostate Risk Assessment score.
Urology. 2008;72(2):396-400.
12. Cooperberg MR, Freedland SJ, Pasta DJ, et al.
Multiinstitutional validation of the UCSF cancer
of the prostate risk assessment for prediction of
recurrence after radical prostatectomy. Cancer.
13. May M, Knoll N, Siegsmund M, et al. Validity of the
CAPRA score to predict biochemical recurrencefree survival after radical prostatectomy. Results
from a European multicenter survey of 1,296
patients. J Urol. 2007;178(5):1957-1962.
14. Lughezzani G, Budaus L, Isbarn H, et al.
Head-to-head comparison of the three most
commonly used preoperative models for
prediction of biochemical recurrence after radical
prostatectomy. Eur Urol. 2010;57:562-568.
15. Cooperberg MR, Broering JM, Carroll PR. Risk
assessment for prostate cancer metastasis and
mortality at the time of diagnosis. J Natl Cancer
Inst. 2009;101(12):878-887.
16. Schroder FH, Hugosson J, Roobol MJ, et al.
Screening and prostate-cancer mortality in a
randomized European study. N Engl J Med.
17. Cooperberg MR, Broering JM, Carroll PR. Time
trends and local variation in primary treatment
of localized prostate cancer. J Clin Oncol.
18. Esserman L, Shieh Y, Thompson I. Rethinking
screening for breast cancer and prostate cancer.
JAMA. 2009;302(15):1685-1692.
Back Issues of
PCRI Insights
are Available at
www.PCRI.org • PCRI Insights
PCRI Insights, November 2010, Vol 13: No 4
Prostate MRI: Information for
Patients and Families
Daniel J A Margolis, MD
Co-Director, Prostate MRI
Adjunct Clinical Professor of Radiology
David Geffen School of Medicine at UCLA
rostate cancer affects nearly all of our lives,
but it affects different people in different ways.
Sometimes an abnormal blood screening
test (for PSA, prostate specific antigen) will suggest
cancer, but none is found at biopsy. Sometimes
a decision has to be made whether to treat what
appears to be a very small amount of cancer
and risk the associated side effects. Sometimes
a patient who is thought to be a good surgical
candidate will turn out to have cancer that cannot
No other imaging technique is
as good as MRI for delineating
the prostate and surrounding
tissues and detecting cancer
within the prostate
be treated surgically. One new consideration is,
with stereotactic radiosurgery and robotic-assisted
laparoscopic surgery, can we formulate a more
accurate treatment plan ahead of time? All of these
are issues where prostate MRI (magnetic resonance
imaging) can potentially provide value.
PCRI Insights • www.PCRI.org
We all know that prostate cancer is the most
common (non-skin) cancer and second leading cause
of cancer death in American men, but it has relatively
low mortality (death rates) compared with many other
cancers such as lung, breast, and colon(1). In other
words, most men die with prostate cancer, but not
from it. The challenge, then, is to try to find all prostate
cancer but treat only that cancer which is aggressive.
Currently, the standard of care is to screen men with
a blood test and physical examination (digital rectal
examination) and perform “sextant” biopsies, or two
biopsies each on the right and left side of the prostate at
The challenge is to try to find all
prostate cancer but treat only
that cancer which is aggressive
each of the three levels (apex, midgland, and base). The
difficulty is that aggressive prostate cancer may only be
found in a small proportion of the prostate, such that
biopsies, which sample only a very small proportion of
the prostate, may find only non-aggressive cancer or
none at all. Because we do not want to let anyone die
of prostate cancer, even a small amount of aggressive
cancer is considered a reason to consider treatment.
Prostate MRI is not designed to replace the current
practices (at least not yet). However, it can be helpful
for physicians in specific situations. Some uses been
well studied at academic medical centers and have
become part of the work-up of prostate cancer at these
centers. Other indications are rather new and relatively
unproven, with few supportive studies in the medical
literature, but many show promise and may enter the
standard clinical arena soon.
There are 4 ways that prostate MRI has been shown
useful in the work-up of prostate cancer
1. Surgical Planning
2. Suspicious PSA, Negative Biopsies
3. Radiation Therapy Planning
4. Abnormal PSA After Surgery or Radiation
Therapy, “Biochemical Failure”
Surgical Planning
Although most surgeons neither use nor really need
MRI for surgical planning, there are certain cases where
it is useful. For the most part, a surgeon’s ability to
palpate, or feel, the location of cancer tells him or her
where to cut. Most surgeons will try to cut out all of
the cancer but, if at all possible, spare the nerves next
to the prostate which are important for continence and
erectile function. The prostate tissue will be examined
by a pathologist, and this report will help the surgeon
decide if radiation therapy is needed after surgery.
In some cases, it can be determined prior to surgery
from the PSA level and biopsies that there is an intermediate chance that the patient would need radiation therapy regardless. In these cases, it might make sense to
proceed directly to radiation therapy and spare the additional risks of surgery. MRI can be used to determine if
all of the cancer is confined within the prostate, which is
necessary to prevent the need for radiation therapy(2).
With advent of interest in robot-assisted laparoscopic prostate surgery, or “robotic surgery,” surgeons
have an immense improvement in control over the
surgical field, and are able to see and cut with much
finer detail. The only drawback is the loss of palpation,
such that surgeons cannot “feel” where the cancer lies.
Many will simply cut as close to the nerves as is safe.
However, some surgeons are using MRI as a road map,
Dr. Daniel Margolis
Adjunct Clinical Professor of Radiology
David Geffen School of Medicine
at UCLA, Los Angeles CA
Dr. Margolis received his MD from USC,
Los Angeles in 1998 and did his diagnostic
radiology residency at UCLA. He was
Associate Clinical Professor of Radiology
at Stanford University, Stanford CA in
2005-6. He then joined UCLA where he is
Co-Director, Prostate MRI, and Adjunct
Clinical Professor of Radiology - David
Geffen School of Medicine.
in lieu of palpation, to determine how to plan their surgeries. This way, they can decide to cut closer to the
prostate when it is safe which improves the chances
of preserving nerve function, or to give the prostate a
wide berth, in those cases where the cancer extends to
the edge of the prostate or even slightly beyond. Surgeons can even vary the surgical technique between
right and left if one side is safer than the other(3).
Suspicious PSA
But Negative Biopsies
One of the most frustrating and anguishing situations for patients and physicians alike is when the
PSA blood test is suspicious, because it is high or rising rapidly, but the biopsies are negative. In this case,
the concern is that the biopsies missed the cancer.
However, in some cases, the blood test is abnormal
because of a benign condition, (Continued on page 10)
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such as BPH (benign prostatic hyperplasia) or inflammation referred to
as prostatitis. Because it is so important to determine whether or not a
patient has aggressive (or any) cancer, some patients would undergo
up to three or four repeat biopsies.
MRI can find a suspicious area in the
prostate in many if not most cases
for targeting(4). Some centers can
even biopsy a suspicious area during
an MRI scan, although this is usually
scheduled as a second scan because
the hardware is different.
Radiation Therapy Planning
External-beam radiation planning is usually done with a CT scan.
Some centers, which use stereotactic body radiation therapy
(SBRT) that combines image-guided and intensity-modulated (IGRT
and IMRT) techniques, use a CT
scan to plan where to irradiate after metallic beads, “fiducial markers,” have been placed. However,
the prostate appears as a gray blob
on CT scan. MRI can delineate the
prostate in exquisite detail, which
is useful in guiding the radiation
beams to treat just the cancer
and spare the adjacent structures
such as the rectum, bladder, and
nerves. MRI can also be used to
identify suspicious bone lesions
and enlarged lymph nodes which
could also be treated(5).
Conventional brachytherapy,
a technique in which radioactive
seeds are placed in the prostate, is a
well-established treatment for early
stage prostate cancer. High-dose
brachytherapy instead uses rods,
called catheters, which are inserted into the prostate through which
highly radioactive seeds are temporarily placed into the prostate and
then removed. It has the advantage
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that specific areas in the prostate
can be targeted. This has a very low
incidence of side effects but is only
effective for cancer confined to the
prostate. MRI can be used to help
determine which are the most suspicious areas in the prostate that
need a “boost” of radiation, and to
confirm that the prostate cancer is
all confined to the prostate.
“Biochemical Failure,” Abnormal
PSA After Therapy
Successful treatment of prostate
cancer should result in a “negative”
or undetectable blood level of PSA.
In some cases, the PSA begins to
rise again. This suggests that some
prostate cancer may be left. Treatment choices at this point are limited, and it becomes important to determine where the cancer might be.
MRI is sensitive for prostate cancer
which may have survived radiation
therapy, both in the prostate and in
the pelvic lymph nodes and bones,
and can sometimes find recurrence
in the pelvis after the prostate is
surgically removed. Other types of
scanning (CT, PET, ultrasound) are
less sensitive.
There are also 3 methods which
are being actively investigated but
are not widely available.
1. Active Surveillance
2. Biopsy Planning
3. Focal Therapy Planning
Active Surveillance
One choice for men who only
have a very small amount of nonaggressive prostate cancer is active surveillance, previously called
“watchful waiting.” Rather than
treating the prostate cancer right
away, these patients return at regular intervals for a repeat physical examination, blood test, and (usually
at longer intervals) repeat biopsy.
Despite some confusing and alarming suggestions that biopsies can
actually make cancer worse, this has
never been proven. However, biopsies are uncomfortable and have
the common risks involved with any
invasive procedure, and the inflammation from repeat biopsies can
make eventual surgery difficult.
MRI has two advantages for
active surveillance. First, it can
identify areas in the prostate that
are suspicious for aggressive cancer
that might have been missed by the
biopsies(6). This would indicate
the need for a targeted biopsy
of the suspicious area to ensure
that immediate treatment is not
necessary. Additionally, MRI can
be used for follow-up instead of
biopsies, which is much safer and
less uncomfortable.
Biopsy Planning
MRI has already been shown
useful for locating prostate cancer
when the blood test is abnormal
but biopsies are negative. Some
physicians have advocated for
performing MRI before the
biopsy, in order to target the most
suspicious area the first time. Not
only does this make biopsies more
straightforward, but it lessens the
likelihood of “undersampling,” the
term used when the biopsies miss
the aggressive cancer and only find
non-aggressive cancer. This risk of
undersampling is the basis by which
we recommend treatment of nonaggressive prostate cancer, over
the concern that more aggressive
cancer may have been missed.
Biopsy planning is a rapidly
developing area. Previously, the
MRI images and report would describe the area in question, which
the physician performing the
ultrasound-guided biopsy would
then try to locate using anatomic
landmarks. Now, new software is
trying to fuse the MRI and ultrasound images, so the physician
can see the corresponding MRI
images of the needle trajectory.
Other centers are developing a
dedicated MRI setup for MRIguided biopsies.
Focal Therapy Planning
Current conventional treatment
for prostate cancer consists of chemotherapy including hormonal
therapy, surgery, radiation therapy
and cryotherapy. New techniques
which have been proposed include
HIFU (high intensity focused ultrasound, where sound waves agitate
and heat tissue, destroying tumor
cells), HIFU (high intensity focused
ultrasound, where sound waves
agitate and heat tissue, destroying
tumor cells) and IRE (irreversible
electroporation, where an electric
current selectively destroys tumor
cells). These techniques are very
promising, but none have really
gained clinical acceptance, and the
last is not yet clinically available.
One of the components of these focal techniques, which can pinpoint
areas to treat in and around the
prostate, is that they require imaging guidance. Because no technique is as good as MRI for delineating the prostate and surrounding
tissues and detecting cancer within
the prostate, it is the logical choice.
MRI has the advantage that it can
also measure temperature for both
freezing and heating techniques(7).
What Does Prostate MRI Involve?
The basic physical principles
behind MRI have been the subject
of two Nobel prizes. MRI takes
advantage of the fact that each
hydrogen atom functions like its
own spinning magnetic compass.
By sending a fluctuating magnetic
field through a patient and then
Combine 5 MRI Techniques for Best Cancer Detection
T1 weighted imaging
Mainly used to detect
T2 weighted imaging
Standard “Tissue Contrast”
Diffusion-weighted imaging
Highly sensitive for cancer
detection, but lower resolution
Perfusion imaging or Dynamic
Contrast Enhancement
Localizes cancer based on its
disordered blood supply
Magnetic resonance
spectroscopic imaging (MRSI)
Has the poorest spatial
resolution, but is the most
specific test for identifying
aggressive prostate cancer
detecting eddies in the resultant
magnetic field, one can (using
some quite complicated mathematics that involves terms like
“inverse Fourier transform” and
“spin-lattice relaxation”) generate a
picture of the tissues of the human
body. Prostate MRI uses this amazing property and adds up to three
additional techniques to optimize
detection of prostate cancer.
T2-weighted imaging is the
standard “tissue contrast” imaging
we use to identify the prostate and
surrounding structures such as
the seminal vesicles, bladder, and
neurovascular bundles. Cancer
and some other conditions appear
similar on T2-weighted imaging, so
we have to use the other techniques
to determine which areas are truly
suspicious. T1-weighted imaging
is primarily used for detection of
hemorrhage, which can confuse the
appearance of T2-weighted imaging
and diffusion-weighted imaging.
Diffusion-weighted imaging uses
the principle of Brownian motion,
or the movement of free water
molecules. Water motion is more
restricted in densely packed cells,
such as prostate cancer. MRI can
use directional pulses to detect the
degree to which free water motion
is restricted. This has been shown
to be highly sensitive for detection
of prostate cancer, although it is
lower resolution than standard MRI
tissue imaging(8).
Perfusion imaging, or dynamic
contrast enhancement, takes advantage of the fact that MRI imaging is completely safe for patients
with normal or near-normal kidney
function and no implanted iron or
electronic devices. One can repeatedly scan (Continued on page 12)
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the same area. When a contrast
dye containing the rare earth element gadolinium is injected intravenously, the blood vessels light
up. By mapping which areas light
up first and brightest, and which
wash out earliest, one can localize cancer based on its disordered
blood supply(9).
MRI Endorectal Coil
Technically, the dynamic contrast
enhancement images are also T1weighted, but they are analyzed
by a workstation to generate the
perfusion maps.
Finally, magnetic resonance
spectroscopic imaging (MRSI)
allows for the measurement of
small molecules throughout the
prostate. The molecules of interest are citrate, a normal component of prostate cells which
is consumed in high metabolic
states such as cancer, and choline,
which is elevated during rapid
cellular membrane turnover, also
common in cancer. When the ratio of citrate to choline flips, this
is an indication of aggressive cancer. Although MRSI has the poorest spatial resolution, it is the
most specific test for aggressive
prostate cancer(10).
Spectroscopy is tricky. No
multicenter study has shown
benefit, but many single-center
studies at “centers of excellence”
have shown benefit from MRSI
(12,13,14, 15). Therefore, one
should only get spectroscopy
done where there are specialists
in its use for prostate cancer.
Fortunately, dynamic contrast
enhancement and diffusionweighted imaging mostly
compensate for the lack of
spectroscopy in most cases.
Some prostate MRI is acquired
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MRSI (Magnetic Resonance Spectroscopic Imaging) is the
most specific test for identifying aggressive prostate cancer
using a special “coil,” which is the
name for the antenna that listens
to the echoes in the magnetic
field. If very high spatial resolution is necessary, a specially designed coil is placed in the rectum
adjacent to the prostate. This
coil is actually just a loop of wire,
but it has a small balloon around
it that helps hold it in place. In
some cases, mostly those where
the lining or “capsule” of the
prostate does not need to be accurately outlined and when spectroscopy is not ordered, imaging
can be done without the special
coil at a cost of some loss of resolution(11).
The MRI itself is otherwise relatively uneventful. Most patients
will receive an injection of a hormone called “glucagon” in a shoulder muscle which will prevent the
rectum from spasming for about an
hour. There are no lasting effects of
this medicine, but because it can interfere with insulin, diabetics who
take insulin must not receive it.
Otherwise, one lies on ones back
for about 45 minutes. The scan is
noisy, but other than the injection
of contrast, patients do not feel
anything during the exam. It is important that the hips remain perfectly still, as the scans are planned
based on the initial images.
Prostate Endorectal Coil
Because prostate MRI scans
consist of multiple components,
processing the information can take
up to 24 hours. Afterwards, the
referring physician will have access
to the report and, in most cases,
the images.
offers significantly higher
signal-to-noise ratio
Most insurance, including Medicare, will cover a pelvic MRI with
contrast, which is how insurance
companies think of prostate MRI.
However, many insurance companies (again, including Medicare) will
not cover spectroscopy. Spectroscopy is much harder to do well, and
there is no simple way for insurance
companies to know that they are
getting their money’s worth when
they pay for it, so in general, they
will not. Most imaging centers will
allow patients to pay out-of-pocket
for this component, but it can cost
hundreds of dollars. If it is not covered, the patient and referring physician must decide if it is worth it.
How Does One Know
If Prostate MRI Is Necessary?
Like many medical tests, prostate MRI is ordered by a physician
– a patient cannot schedule a scan
without a doctor’s order. This is a
legal requirement, but it also means
that patients must have a discussion
with their physician in order to determine if prostate MRI is necessary,
and what kind of MRI the physician
should order. Prostate MRI is only a
part of the diagnosis and management of prostate cancer and is only
necessary in specific cases. However, both the technology behind prostate MRI and the understanding of
its uses are improving every day, so
cases which might have benefitted
from MRI in the past might all but
require it now. In some cases, the
doctor treating the prostate cancer
will need to discuss the matter with
a radiologist, a specialist in medical imaging, in order to determine
what kind of MRI is best and when
it would be useful, and to make certain the necessary hardware and
software is available. This is a relatively young technology and we are
only beginning to understand how
to use it in patient management,
but it holds tremendous potential
to finally help distinguish patients
with non-aggressive cancer who do
not need treatment from those with
aggressive disease who do.
There are certain cases where
prostate MRI should not or must not
be done. Patients with implanted
medical devices, like pacemakers,
cannot undergo MRI. Some new
device designs purport to be MRIcompatible, but none are commercially available. Patients with metal
in their bodies, especially those who
have been exposed to welding or
MRI holds tremendous
potential to finally help
distinguish patients with
non-aggressive cancer who
do not need treatment
from those with aggressive
disease who do.
lathe work, must be screened for
implanted metal in the eyes or other
exposed regions. Patients with hip
replacements or metal screws in the
hips or pelvis can often be imaged,
but the metal can cause artifacts on
the image, and distort the magnetic
field such that diffusion-weighted
imaging and spectroscopy cannot be performed. Also, most MRI
units have a weight limit, usually between 250-400 lbs. Older high-field
magnets often have more stringent
weight limits, but low-field and open
magnets are not powerful enough to
give the kind of information needed
for prostate imaging. Finally, patients with kidney failure might not
be able to receive contrast, depend-
ing on how much kidney function is
left. Claustrophobia is a “relative
contraindication” as it can often be
treated by a sedative prescribed by
the referring physician. Most imaging centers are not set up to sedate
patients once they arrive, but patients can take medicine prescribed
by their referring physicians.
1. Institute NC. Cancer Trends Progress Report – 2009/2010
Update. Bethesda, MD: NIH, DHHS; 2010 [April, 2010];
Available from: http://progressreport.cancer.gov.
2. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI,
Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology. 2001;58(6):843-8.
3. Hricak H, Wang L, Wei DC, et al. The role of preoperative endorectal magnetic resonance imaging in the decision
regarding whether to preserve or resect neurovascular
bundles during radical retropubic prostatectomy. Cancer. 2004;100(12):2655-63.
4. Lawrentschuk N, Fleshner N. The role of magnetic resonance imaging in targeting prostate cancer in patients with
previous negative biopsies and elevated prostate-specific
antigen levels. BJU Int. 2009;103(6):730-3.
5. Westphalen AC, McKenna DA, Kurhanewicz J, Coakley FV. Role of magnetic resonance imaging and magnetic resonance spectroscopic imaging before and after radiotherapy
for prostate cancer. J Endourol. 2008;22(4):789-94.
6. Turkbey B, Pinto PA, Mani H, et al. Prostate cancer: value
of multiparametric MR imaging at 3 T for detection--histopathologic correlation. Radiology. 2010;255(1):89-99.
7. Siddiqui K, Chopra R, Vedula S, et al. MRI-guided Transurethral Ultrasound Therapy of the Prostate Gland Using
Real-time Thermal Mapping: Initial Studies. Urology. 2010.
8. Desouza NM, Reinsberg SA, Scurr ED, Brewster JM, Payne
GS. Magnetic resonance imaging in prostate cancer: value
of apparent diffusion coefficients for identifying malignant
nodules. Br J Radiol. 2007.
9. Puech P, Potiron E, Lemaitre L, et al. Dynamic contrastenhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical prostatectomy specimens. Urology. 2009;74(5):1094-9.
10.Fuchsjager M, Akin O, Shukla-Dave A, Pucar D, Hricak H. The role of MRI and MRSI in diagnosis, treatment selection,
and post-treatment follow-up for prostate cancer. Clin Adv
Hematol Oncol. 2009;7(3):193-202.
11.Heijmink SW, Futterer JJ, Hambrock T, et al. Prostate
cancer: body-array versus endorectal coil MR imaging at
3 T--comparison of image quality, localization, and staging
performance. Radiology. 2007;244(1):184-95.
12.Prostate cancer: value of multiparametric MR imaging at 3
T for detection--histopathologic correlation Turkbey B, Pinto
PA, Mani H, Bernardo M, Pang Y, McKinney YL, Khurana K,
Ravizzini GC, Albert PS, Merino MJ, Choyke PL., Radiology. 2010 Apr;255(1):89-99.
13.M RI in the detection of prostate cancer: combined apparent diffusion coefficient, metabolite ratio, and vascular
parameters. Riches SF, Payne GS, Morgan VA, Sandhu S,
Fisher C, Germuska M, Collins DJ, Thompson A, deSouza
NM., AJR Am J Roentgenol. 2009 Dec;193(6):1583-91.
14.P rostate cancer detection: comparison of T2-weighted
imaging, diffusion-weighted imaging, proton magnetic
resonance spectroscopic imaging, and the three techniques combined. Chen M, Dang HD, Wang JY, Zhou
C, Li SY, Wang WC, Zhao WF, Yang ZH, Zhong CY, Li GZ. Acta Radiol. 2008 Jun;49(5):602-10.
15.P rostate cancer: identification with combined diffusionweighted MR imaging and 3D 1H MR spectroscopic imaging--correlation with pathologic findings. Mazaheri Y,
Shukla-Dave A, Hricak H, Fine SW, Zhang J, Inurrigarro G,
Moskowitz CS, Ishill NM, Reuter VE, Touijer K, Zakian KL,
Koutcher JA. Radiology. 2008 Feb;246(2):480-8.
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PCRI Insights, November 2010, Vol 13: No 4
Progress in Prostate
Cancer: Targeted Biopsies
and Active Surveillance
Inderbir Gill, Osamu Ukimura, Mitchell Gross, David Agus
Center for Advanced Robotic & Laparoscopic Surgery and Center for Applied
Molecular Medicine
USC Institute of Urology,
USC Westside Prostate Cancer Center,
Keck School of Medicine,
University of Southern California, Los Angeles, California
linically localized prostate cancer is a heterogeneous entity. Prognosis depends upon various factors such as PSA level, clinical exam,
and histologic grade (Gleason score). While much of
the therapeutic research has focused on the higher-risk
patients, the majority of contemporary prostate cancer
patients are classified as having a low- or intermediaterisk form of the disease. The long natural history of
low-risk prostate cancer and the presence of competing risks in an otherwise elderly male population all
contribute to the problem of over-treatment of primary
prostate cancer. Herein we discuss our approach for
low-risk prostate cancer at the University of Southern
California (USC) Institute of Urology focusing on our
targeted prostate biopsies and active surveillance as
components of our overall program which aims to individualize patient care based on understanding prostate
cancer on a “per lesion” as well as a “per patient” basis.
Targeted Prostate Biopsies
Currently, the standard approach for diagnosing prostate cancer involves performing systematic, non-targeted
biopsies (10-12 cores) performed with trans-rectal ultrasound (TRUS) guidance. In routine clinical use, TRUS
is used primarily to direct biopsies along loosely defined
anatomic regions of the prostate gland (right/left, medial/
lateral, base/mid/apex). A limitation of routine TRUS
imaging is its general lack of accuracy to reliably and
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reproducibly identify and sample prostate cancer lesions.
The limitations of current prostate biopsy strategies are
highlighted by studies which demonstrate that in patients
with biopsy-proven prostate cancer who are enrolled in
active surveillance protocols, repeat biopsies reveal only
40-45% to have the same Gleason score as in their initial
biopsy; 30% of repeat biopsies reveal no cancer, and 1520% of repeat biopsies are upgraded to a higher Gleason
score [1-2]. It remains unclear if this discrepancy between initial and repeat biopsies represents true cancer
progression, or merely reflects sampling error. Many believe it is more likely the latter.
At the USC Institute of Urology, we have recently
developed an innovative, computer-based prostate
biopsy approach which utilizes MRI/TRUS fusionguidance. The approach is based on an ultrasound
technology which provides for a 3-dimensional image of
the prostate. Except for this specialized ultrasound and
computer equipment, the biopsy procedure is otherwise
the same (and takes about the same amount of time)
as a standard biopsy routinely performed in outpatient
settings. Overall, this approach allows us to perform
precisely targeted biopsies aimed of suspicious prostate
lesions identified on dynamic contrast enhanced (DCE)
MRI and/or TRUS imaging. In addition, the precise
intra-prostatic location of a given cancer lesion or a
needle biopsy location can now be documented with
millimeter accuracy. Re-biopsy of the exact location
David B. Agus, M.D.
Professor of Medicine
Director, USC Center for
Applied Molecular Medicine
Director, USC Westside Cancer
Keck School of Medicine
University of Southern California
Dr. Agus’ research focuses on the
application of proteomics and genomics
for the study of cancer and the
development of new therapeutics for
cancer, where he develops clinical
trials for new drugs and treatments for
cancer. Dr. Agus received his M.D.
from the University of Pennsylvania.
He was a Howard Hughes Medical
Institute-NIH Research Scholar, did
his medical internship and residency
training at Johns Hopkins Hospital,
and completed his oncology fellowship
training at Memorial Sloan-Kettering
Cancer Center. He is the founder of
Oncology.com, the largest cancer
internet resource/community, Applied
Proteomics, and of Navigenics, a health
care technology and wellness company.
of a previously positive biopsy site within the prostate is
also feasible. In other words, our team now has the ability
to precisely record, and re-visit, with high accuracy, any
geographical site of biopsy-proven cancer lesion within
the prostate. Such capability has hitherto been unavailable.
It is likely that such high precision biopsies may allow
more individualized decision-making based on “per
prostate lesion” data to properly select patients for active
surveillance, focal therapy, or radical treatments.
Figure 1: The images below demonstrate our targeted
biopsy technique based on MRI and TRUS image-fusion
guidance. The green lines indicate biopsies that were
negative for cancer; the red lines indicate biopsies positive
for cancer. Note: Each biopsy is spatially-registered and
serially numbered, thus providing intra-prostatic geographic
localization [3].
Active Surveillance: Overview
The high incidence of clinically occult prostate cancer discovered at autopsy, the side effects of radical
therapies, and the low risk of progression following
treatment has led to development of less aggressive
treatment strategies. “Active surveillance” is an approach incorporating regular clinical follow-up without
intervention for select low-risk sub-groups of prostate
cancer patients. Several studies have reported on the
relative safety, as regards cancer outcomes with relatively short follow-up, for patients treated with active
surveillance [4-5]. While there are differences in how
patients for active surveillance are selected, generally
these studies include patients with very low risk prostate cancer defined by:
(Continued on page 16)
FIGURE 1: MRI and TRUS Image-Fusion Guidance
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low PSA (PSA< 10 ng/ml, PSA
density ≤0.15 ng/ml/cm3); low
volume cancer; low-grade histology (typically Gleason sum 3+3=6
in ≤ 2 biopsy cores), and low clinical stage (T1c). Similarly, while
there are significant differences in
how patients are deemed to have
“progressed” from active surveillance, a general consensus has
developed around factors such as
pathologic progression (increase
in Gleason score and/or number of
cores involved with cancer), rapid
PSA progression (defined as short
PSA doubling time), and clinical
progression on digital rectal exam.
In addition, a significant number of
patients (25-30%) decide to withdraw from active surveillance and
cross-over to radical therapies for
various reasons such as “anxiety”
or “patient preference.” There exists a need to better define patients
enrolled in watchful waiting protocols, by developing a “targeted
active surveillance” strategy that
incorporates monitoring on a “per
lesion” basis rather than the current
whole gland approach. Such an approach would possibly be based
on spatially-directed biopsy techniques, mentioned above.
A New Paradigm: Targeting Prostate
Cancer on a “Per-Lesion” Basis
We believe that, for patients
with low-risk disease, a new paradigm centered around the concept
of treatment on a “per lesion” rather than a �whole gland’ basis is attractive. Detailed pathologic study
of radical prostatectomy specimens
suggests that the prostate typically
harbors many geographically defined cancer nodules and genetically distinct clones. Recent evidence
suggests that a primary tumor focus, an “index lesion,” is present
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is most patients which ultimately
drives the natural history of prostate cancer [6]. In most cases, this
“index lesion” can be distinguished
by its larger size (several-fold larger than secondary lesions) and the
presence of aggressive pathologic
features such as Gleason pattern
4/5 or extra-prostatic extension.
Further support for the concept of
an index lesion comes from detailed molecular studies in patients
with metastatic prostate cancer,
which indicates a monoclonal origin of metastasis in lethal prostate
cancer. For example, a study of 94
tumors obtained from 30 subjects
who died from prostate cancer indicated that a common pre-cursor
cell gave rise to the wide-spread
metastasis [7]. The existence of an
index lesion has major implications
for the care of prostate cancer patients. If an index lesion contains
a clone with metastatic potential,
it could be targeted and destroyed.
Conversely, cancerous areas which
do not harbor these “lethal” clones
could potentially undergo surveillance without intervention. While
some initial efforts have focused
on the minority of prostate cancer
patients with unilateral or unifocal
prostate cancer as potential candidates for sub-total therapies, a
more sophisticated approach will
be needed to define and characterize the index lesion concept for
the majority of prostate cancer patients.
We believe that serial “per lesion”
monitoring, based on geographically-precise biopsies of cancer lesions,
as mentioned above, could provide
new insights. Taken collectively, we
believe that a greater understanding
of prostate cancer on a “per lesion”
basis has considerable potential to
transform patient care.
In summary, we are at a new
stage in approaching the diagnosis
and treatment of prostate cancer.
Technological innovations linking
imaging and surgery allow for an
unprecedented ability to understand
prostate cancer on a “per lesion”
basis. This insight will allow for
greater diagnostic accuracy and,
along a greater understanding of
gene and protein changes (genomics
and proteomics) which underlie the
development and progression of
cancer, will allow for a personalized
treatment plan for patients diagnosed
with prostate cancer.
In some
consisting of active surveillance
may be appropriate.
In other
patients, interventional therapy with
modalities such as minimally invasive
radiation, or even focal ablation
may be considered. Overall, a new
era is ahead where the clinician, the
researcher, and the patient will team
to get the best outcome for each
individual situation.
Dr. Agus answers some
questions from editor
Nathan Roundy
1. Is prostate MRI the �standard
of care’ at your clinic?
Prostate MRI is standard of care
in our clinic for the appropriate
patient. The next question would
be – who is the appropriate
patient. To me, the appropriate
patient is not yet defined, but
as part of the clinical trial we
are doing is all patients who are
indicated for biopsy as part of
an active surveillance program
or are suspected of having a low
volume cancer.
2 In Figure 1 you show a targeted
biopsy image by itself. Does that
mean you would not initial biopsy
any prostate area not indicated by
MRI? Or do you routinely sample
the complete prostate with emphasis
on identified suspicious areas?
We do traditional expanded
sextant biopsies, followed by
targeted biopsies of the lesions
identified by the dynamic
contrast enhanced MRI.
3. Before repeat biopsies, do you
also repeat MRI?
Yes, we repeat the dynamic
contrast enhanced MRI prior
to repeat biopsy to fuse with
the ultrasound image.
4. Do you only biopsy known
lesions on repeat biopsy?
We again perform traditional
expanded sextant biopsies of
the entire prostate, followed by
targeted biopsies of the lesions
identified by the dynamic
contrast enhanced MRI.
5. What MRI technology do
you use? 3.0 Tesla? EndoCoil?
Diffusion? Spectroscopy?
We use a routine 3.0 Tesla
MRI with dynamic contrast
enhancement and fuse this image
with prostate ultrasound. There
is no use of an endorectal coil.
6. Regarding your MRI experience, do you have any statistics
about sensitivity and specificity?
The dynamic contrast enhanced
MRI studies were done in
collaboration with the University
of Lille in France and were able
to identify cancer lesions 0.5 cc
or greater with an 86% sensitivity
and a 94% specificity with an area
under the curve of 0.874 [8]. Pretty
encouraging for a new technology.
7. For our readers, 86% sensitivity means MRI found the cancer
86% of the time, and only 14% of
the time did MRI miss the cancer.
And 94% specificity means only
6% of the lesions MRI identified as
something unusual, were not identified as cancer.
Without going into the statistics,
that is basically correct.
8. How long have you been using
this targeted biopsy approach in
your clinic, and do you have any
statistics you can share?
We have been using this approach
for the past year. It is too early
to give exact statistics, but we do
have a cancer detection rate in the
60-70 percent range in patients
referred (a selected population).
9. Are you accepting patients
into this program? If so who do
they contact?
We are accepting patients into the
targeted biopsy program, the robotic
laparoscopic prostatectomy program,
as well as the care of patients with
prostate cancer.
For oncology services of Drs. Agus
and Gross: 310-272-7640 (USC
Westside Prostate Cancer Center,
9033 Wilshire Blvd, Beverly Hills).
For targeted biopsy program and the
robotic laparoscopic prostatectomy
program, Drs. Gill and Ukimura,
USC Institute of Urology, (323) 8653707, USC Norris Comprehensive
Cancer Center, 1441 Eastlake
Avenue, Los Angeles, CA (and
beginning January, 2011 biopsies
and follow up care will be also at
the USC Westside Prostate Cancer
Center in Beverly Hills).
10. Would you accept a patient
who wanted an MRI, targeted
biopsy, and evaluation, but who
maybe lives in a distant city and
wants follow-up in his home town.
How many days would that workup require?
Yes, we routinely do both the
MRI and targeted biopsy in the
same day; requires just a one
day stay. We recommend follow
up at our clinic for results and
arranging follow up care, but
realize that this is not always
possible and also do telephone
consultations for follow up.
1. Roehl, K.A., J.A. Antenor, and W.J.
Catalona, Serial biopsy results in
prostate cancer screening study. J
Urol, 2002. 167(6): p. 2435-9.
2. Khan, M.A., et al., Can prostate specific antigen derivatives and pathological parameters predict significant
change in expectant management
criteria for prostate cancer? J Urol,
2003. 170(6 Pt 1): p. 2274-8.
3. Mozer, P., et al., Mapping of transrectal ultrasonographic prostate biopsies: quality control and learning
curve assessment by image processing. J Ultrasound Med, 2009. 28(4): p.
4. Klotz, L., et al., Clinical results of
long-term follow-up of a large, active surveillance cohort with localized
prostate cancer. J Clin Oncol, 2010.
28(1): p. 126-31.
5. Tseng, K.S., et al., Risk stratification
of men choosing surveillance for low
risk prostate cancer. J Urol, 2010.
183(5): p. 1779-85.
6. Ahmed, H.U., The index lesion and
the origin of prostate cancer. N Engl J
Med, 2009. 361(17): p. 1704-6.
7. Liu, W., et al., Copy number analysis
indicates monoclonal origin of lethal
metastatic prostate cancer. Nat Med,
2009. 15(5): p. 559-65.
8. Puech, P., et al., Dynamic contrastenhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical
prostatectomy specimens. Urology,
2009. 74(5): p. 1094-9.
www.PCRI.org • PCRI Insights
PCRI Insights, November 2010, Vol 13: No 4
Mark Scholz, MD.
rostate cancer needs testosterone to survive. Blocking testosterone is proven to prolong life in randomized prospective trials. Testosterone Inactivating Pharmaceuticals (TIP), otherwise known as
androgen deprivation or hormone blockade, are FDA approved medicines used either alone or with
radiation to treat various stages of prostate cancer. Despite widespread experience, there are many controversies about the optimal way to use TIP. Probably the biggest issue is side effects. TIP impacts quality of
life. So there is an art to picking the right amount of TIP for each individual. The goal is to continue TIP
long enough to get the job done, but stop before going too long. The optimal methodology for using TIP
varies from situation to situation because prostate cancer comes in a spectrum of “stages” ranging from
low-risk which can be safely monitored without immediate treatment, to metastatic castrate-resistant disease. Between these two extremes are intermediate-risk, high-risk, seminal vesicle invasion (stage T3b),
PSA-relapse and lymph-node metastasis (Stage D1). For more details about low, intermediate and high risk
disease, see the article titled What’s Your Type available at www.pcri.org.
Testosterone, the most common androgen in men, is manufactured intracellularly from cholesterol and progesterone,
mainly in the testicles. Dihydrotestosterone (DHT), a substantially more potent form of testosterone, is converted
from testosterone by the enzyme 5-alpha reductase which is located in the prostate and the liver. Dehydroepiandosterone (DHEA) and androstenedione (ANDRO), weaker androgens, are synthesized in the adrenal glands, located
above each kidney. The adrenal glands are where other common hormones such as cortisone and adrenaline are created. DHEA and ANDRO are synthesized from cholesterol and progesterone just like testosterone (see figure 1).
PCRI Insights • www.PCRI.org
Figure 1: Synthetic Pathway of Testosterone
Prostate cancer can’t survive
without testosterone. The prostate
gland is a vestigial nubbin until after puberty when it blossoms into a
walnut sized gland to manufacture
semen. After puberty, if testosterone
is removed, the gland involutes and
atrophies. Prostate cancer cells are
derived from the prostate gland so
they also need testosterone to survive. Prostate cancer cells grow and
proliferate when testosterone is present; they shrivel and die when testosterone is absent. When testosterone
levels in the blood drop, the cancer
cells “commit suicide” through a
process called apoptosis.
They work by suppressing the pituitary gland (at the base of the brain)
which in turn sends a suppressive
hormonal signal to the testicles.
Testosterone Inactivating
There are different varieties of
testosterone inactivating pharmaceuticals. They fall into three main
categories. In the first category are
the LHRH agonists such as Lupron, Zoladex, Eilgard, and Vantas.
These medicines are administered
by injection on a monthly, quarterly, semi-annual or yearly basis.
The Hypothalamic-Pituitary-Gonadal Axis
In the second category are the
anti-androgens such as Casodex,
Eulexin and Nilutamide. These pills
work at the molecular level to block
testosterone from activating the an-
drogen receptor (the switch in the
cell that enhances cell growth when
its turned on).
In the third category are the
5-alpha-reductase inhibitors such
as Proscar and Avodart. They work
by blocking the conversion of testosterone into its more potent analogue, DHT.
These medications can be
used together in combination to
attain more complete testosterone
suppression and thus increase
the anti-cancer effect. However,
urologists throughout the world
more commonly employ single-drug
therapy with LHRH agonists alone.
This policy is rooted in studies done
back in the 1990’s. These studies
showed that anti-androgens added
to LHRH agonists only enhanced
survival by a couple months1 Also
many urologists at that time were
concerned about the high cost of
Casodex. Unfortunately this policy
of using LHRH agonists without
Casodex persists even though these
days Casodex is generic and much
more affordable.
Adding medicines from the third
category, the 5-alpha reductase inhibitors like Proscar or Avodart, is
often justified with the rationale that,
“It can’t hurt, and it might help.”
While using drugs from all three categories is popular in some circles,
clinical studies are lacking. There
are a number of studies, however,
confirming that Proscar and Avodart
have an anticancer effect. For more
details about using 5-alpha reductase
inhibitors to treat prostate cancer, see
the article titled Proscar and Avodart
at www.pcri.org.
(Continued on page 20)
www.PCRI.org • PCRI Insights
TABLE 1: Studies Showing Survival Advantage with TIP
36 mo. TIP
4 mo. TIP
24 mo. TIP
3 mo. TIP
8 mo. TIP
6 mo. TIP
Casodex by Itself
Clinicians with experience using Casodex as a single agent, so
called anti-androgen monotherapy, have the general sense that:
“Casodex monotherapy is about
70% as effective as the LHRH
agonists but with only 30% of
the toxicity.” Anti-androgens
have been studied in prospective
randomized trials as stand-alone
therapy 2 and combined with radiation. 3 Overall, compared to
LHRH agonists, side effects are
certainly less. And compared
to placebo, they clearly retard
prostate cancer growth. The only
caveat is a higher risk of breast
growth. This can be partially or
completely prevented with prophylactic breast radiation or an
estrogen blocking pill called Femara. For more details on using
Casodex by itself see the article
titled Anti-Androgen Monotherapy
available at www.pcri.org.
PCRI Insights • www.PCRI.org
TIP Added to Radiation
Improves Survival
The most convincing proof
that TIP enhances survival is from
studies of men with intermediaterisk, high-risk and Stage T3b
disease (seminal vesicle invasion)
who are undergoing radiation.
In the studies, little or no TIP is
compared with TIP administered for
a more prolonged period. The two
groups are monitored over time to
determine if one group has superior
survival. The results from several
such trials are listed in Table 1.
As can be seen in Table 1, longer
periods of TIP prolong survival
more that shorter periods. However,
the optimal duration of TIP is still
unknown since treatment periods
between 8 and 24 months are yet
to be tested to see if more than 8
months but less than 24 months
would yield comparable benefit.
This is an important unanswered
question because the side effects
of TIP can be notable. At the
present time our policy is to aim for
somewhere between 12-18 months
of therapy, depending on how well
treatment is tolerated. If side effects
are not excessive, a full 24 months
of therapy can be considered. For
more details on the side effects of
TIP see the article Preventing the
Side Effects of TIP available at
Even without radiation, TIP as a
sole modality can effectively control
prostate cancer for many years. In a
prospective trial in men with proven
lymph node spread (stage D1),
better long-term survival was seen
when TIP was started immediately
as compared to TIP initiated at
the time of cancer progression.10
However, in another prospective
trial with locally advanced prostate
cancer (seminal vesicle invasion or
stage T3b), better survival occurred
when radiation was added to TIP,
compared to men who were treated
with TIP alone.11
To summarize — when the disease is aggressive, TIP and radiation together appear best, but only
up to a point. Once the disease becomes metastatic, TIP alone is considered standard. At the other end
of the spectrum are the men with
intermediate-risk disease. For the
more “favorable type” of intermediate risk disease, combination treatment is overkill. These men should
be treated with one treatment or the
other, not both. Men with the more
“unfavorable type” of intermediate
risk disease should consider combination treatment, but only with
short-term TIP for three or four
than 6-9 months).15,16 So more
and more experts recommend that
TIP be started before the onset of
bone metastasis. Recommendations
vary when it comes to selecting
a predetermined PSA threshold
to begin treatment. Numbers like
5, 10 or 20 are suggested as the
trigger for starting TIP but other
factors, including Gleason score
and PSA doubling time, also need
to be taken into account. PSA alone
fails to portray the whole picture.
For example, Johns Hopkins has
reported that one-fourth of men with
PSA relapse develop bone metastasis
with PSA levels under 10.17
Intermittent TIP
PSA Relapse
Medical experts continue to
debate the advisability of starting
TIP immediately in men with
PSA relapse. The debate is likely
to continue because there are
no prospective trials, only less
definitive retrospective trials.12
The situation is also complicated
by differences between patients —
some men have relapses that are
very slow-paced whereas others
have a type of disease that moves
faster. And many studies confuse
matters by inappropriately jumbling
both groups’ together, making
outcomes difficult to interpret. Not
surprisingly, studies incorporating
men with slowly-paced disease
show no benefit with starting TIP
right after relapse. Such men will do
well whether they have TIP or not.
To reduce side effects, TIP is often given intermittently.18 The idea
of stopping and taking a holiday
from TIP was first floated in the early 1990’s. Back then, discontinuing
treatment seemed crazy. However,
our initial experience with TIP for
men in PSA relapse had made us
feel pretty upbeat about its effectiveness. PSA levels almost always
dropped to zero. With PSA levels so
low the question arose, “Have we
cured the disease?” The only way
to find out was to stop the treatment
and see. As it turned out, cure was
rare. PSA levels started rising once
testosterone in the blood recovered.
Even so, we and others were gratified to learn that TIP could be restarted a second time with a high
likelihood that the PSA would again
drop zero.19
Despite all these conflicting
reports, several studies confirm
that there is a benefit for starting
TIP before the onset of bone
metastasis.13,14 This is seen most
clearly in studies done in men with
faster PSA-doubling times (less
Our ensuing experience using
TIP intermittently was published
in the Journal of Urology.20 We
discovered that a longer initial
treatment period (up to about 12
months) induced a longer holiday
period. Proscar was also shown to
further extend the holiday. More
recently, we have shown that the
off-period can be prolonged further
using medicines that work by stimulating the immune system, medicines such as Leukine, low-dose
cytoxan, Celebrex and Revlimid.21
For more details, see the article
titled Immune Treatment for PSARelapsed Prostate Cancer available at www.pcri.org.
Intermediate-Risk Disease
In the United States, most men with
intermediate-risk disease are treated
with surgery or radiation. When radiation is used, adding four to six
months of TIP gives better cure rates
than radiation by itself.8,9 However,
the intermediate-risk category is a
broad with predicted post-radiation
relapse rates that vary between 10
and 50% depending on the primary
Gleason Grade (4 vs. 3), the degree
of PSA elevation, and the extent of
disease on biopsy. Men with the
more “favorable” type of intermediate-risk disease might consider
either TIP alone (see below) or radiation alone. Men with the “unfavorable” type of intermediate-risk
disease should probably consider
using a short-course of four months
of TIP plus radiation.
TIP Without Radiation
I believe that TIP is a reasonable,
stand-alone treatment for men with
intermediate-risk disease. While
there are limited studies documenting its effectiveness (ref), at Prostate
Oncology Specialists we have treated 120 men with 12 months of TIP
followed by a color doppler directed
biopsy of the previously documented
cancer site. The biopsy was clear of
cancer in 80% of the men.
(Continued on page 22)
www.PCRI.org • PCRI Insights
We have also recently submitted
an article for publication detailing
the twelve-year outcome of 73 men
with an average age of 67 initially
treated with TIP alone. The average PSA for all the men was 9. The
average Gleason score was seven.
Most had a nodule that could be felt
on digital rectal examination. Treatment was started back in the 1990’s
before the advent of the modern
D’Amico staging system (separation of men into low, intermediate
and high-risk categories). When we
went back and assigned risk-categories (during the process of preparing
the publication) men from all three
risk-categories were represented.
Twenty-one of these men (29%)
never needed any further therapy; a
single course of TIP kept their PSA
suppressed indefinitely. Twentyfour men (33%) required periodic
retreatment with TIP (intermittent
TIP) to keep their PSA levels under five. Twenty-eight men (38%),
rather than continuing on intermittent TIP, decided to have local therapy such as surgery, seeds or radiation. Their local therapy was performed, on average, five and a half
years after the first cycle of TIP. Of
these 28 men who had delayed local therapy, only three developed a
PSA relapse and none have developed metastasis.
So clearly, TIP as primary therapy is effective. The problem (as
is the case for all prostate cancer
treatments) is side effects. Fortunately, after treatment is stopped,
testosterone recovers and side effects wear off. Since it is now becoming standard policy to monitor
biopsy-positive low-risk disease in
a standardized approach called active surveillance, we question why
PCRI Insights • www.PCRI.org
active surveillance techniques can’t
be used to monitor men with TIPinduced, biopsy-negative disease?
Criticisms of using TIP as primary
therapy for intermediate-risk disease seem to be based solely on an
unwillingness to deviate from “the
way things have always been done”
rather than any justifiable logic.
The Final Word — Quality of Life
Testosterone deprivation is one
of the most potent treatments ever
known for cancer. Breast cancer
is the only other hormonally
responsive cancer and the antihormones for breast cancer are
only 20% as effective as TIP is for
prostate cancer.
Despite TIP’s potency, quality of
life considerations are critical. The
side effects of TIP can be severe.
When long-term suppressive TIP
is indicated, intermittent treatment
helps. Men who have locally
advanced disease who are taking
TIP with radiation for cure, still
face uncertainties about the optimal
treatment time. The best we can do
is weigh impact of the side-effects
in each individual and balance
them with the known ability of TIP
to improve cure rates.
1. Maximum Androgen Blockade in Advanced Prostate
Cancer: An Overview of the Randomized Trials. The
Lancet 355:1491, 2000.
2. Bicalutamide (150mg) Versus Placebo as Immediate
Therapy Alone or as Adjuvant to Therapy with
Curative Intent for Early Nonmetastatic Prostate
Cancer: 5.3 Year Median Followup from the
Scandinavian Prostate Cancer Group Study Number
6. The Journal of Urology 172:1871, 2004.
3. Bicalutamide 150 mg Plus Standard Care vs Standard
Care Alone for Early Prostate Cancer. Urological
Oncology 97:247, 2005.
4. Improved Survival in Patients with Locally Advanced
Prostate Cancer Treated with Radiotherapy and
Goserelin. The New England Journal of Medicine
337:295, 1997.
5. Ten-Year Follow-Up of Radiation Therapy
Oncology Group Protocol 92-02: A Phase III Trial
of the Duration of Elective Androgen Deprivation
in Locally Advanced Prostate Cancer. Journal of
Clinical Oncology 26:2497, 2008.
6. Survival Benefit Associated with Adjuvant Androgen
Deprivation Therapy Combined with Radiotherapy
for High and Low-Risk Patients with Nonmetastatic
Prostate Cancer. I.J. Radiation Oncology 66:395,
7. Long-Term Followup of a Randomized Study of
Locally Advanced Prostate Cancer Treated With
Combined Orchiectomy and External Radiotherapy
Versus Radiotherapy Alone. The Journal of Urology
176:544, 2006.
8. Final Report of Multicenter Canadian Phase
III Randomized Trial of 3 Versus 8 Months of
Neoadjuvant Androgen Deprivation Therapy Before
Conventional-Dose Radiotherapy for Clinically
Localized Prostate Cancer. I. J. Radiation Oncology
73:327, 2009.
9. Risk of Prostate Cancer Recurrence in Men Treated
With Radiation Alone or in Conjunction With
Combined or Less Than Combined Androgen
Suppression Therapy. Journal of Clinical Oncology
26:2979, 2008.
10. Immediate Hormonal Therapy Compared with
Observation After Radical Prostatectomy and Pelvic
Lymphadenectomy in Men with Node-Positive
Prostate Cancer. The New England Journal of
Medicine 341:1781, 1999.
11. ASCO 2010: Adding Radiation Therapy to Hormone
Therapy Improves Survival in Men with Locally
Advanced Prostate Cancer. NCI Cancer Bulletin 7,
12. Early Versus Delayed Androgen Deprivation for
Prostate Cancer: New Fuel for an Old Debate.
Journal of Clinical Oncology 23:8225, 2005.
13. Immediate or Deferred Androgen Deprivation for
Patients With Prostate Cancer Not Suitable for
Local Treatment With Curative Intent: European
Organisation for Research and Treatment of Cancer
(EORTC) Trial 30891. Journal of Clinical Oncology
24:1868, 2006.
14. Immediate versus deferred treatment for advanced
prostatic cancer: initial results of the Medical
Research Council trial. British Journal of Urology
79:235, 1997.
15. Early Versus Delayed Hormonal Therapy for Prostate
Specific Antigen Only Recurrence of Prostate Cancer
After Radical Prostatectomy. The Journal of Urology
171:1141, 2004.
16. Impact of postoperative prostate-specific antigen
disease recurrence and the use of salvage therapy on
the risk of death. Cancer 116:1887, 2010.
17. Prostate Specific Antigen at the Initial Diagnosis
of Metastasis to Bone in Patients After Radical
Prostatectomy. Journal of Urology 184:157, 2010
18. Potential Benefits of Intermittent Androgen
Suppression Therapy in the Treatment of Prostate
Cancer: A Systemic Review of the Literature.
European Urology 7:49, 2009.
19. Intermittent Androgen Deprivation in Prostate
Cancer Patients: Factors Predictive of Prolonged
Time Off Therapy. The Oncologist 5:45, 2000.
20. Intermittent Use of Testosterone Inactivating
Pharmaceuticals Using FInasteride Prolongs the
Time Off Period. The Journal of Urology 175:1673,
21. Retrospective evaluation of GM-CSF, low-dose
cyclophosphamide, and celecoxib on PSA doubling
time (DT) in men with prostate cancer and PSA
relapse after surgery or radiation. Journal of Clinical
Oncology 28, 2010.
5777 W. Century Boulevard, Suite 800, Los Angeles, CA 90045
(310) 743-2116 • Fax (310) 743-2113 • Website: wwww.pcri.org
November 8, 2010
Dear PCRI Supporters,
More than two million men are afflicted by prostate cancer. Factor in the
spouses, significant others, children and immediate family, prostate cancer
affects more than ten million people in the U.S. We at PCRI have drawn
the line to fight this disease by educating the public, raising awareness,
advocating for the patients and supporting prostate cancer research.
Several treatment therapies, research and pharmaceutical agents
come to market each year. To most patients, these new developments are
overwhelming. They are difficult to understand, especially how they impact
the patient himself, if at all.
Over 200,000 new cases of prostate cancer are diagnosed each year yet
there are very few prostate cancer specialists. As a result, patients are not always getting the most reliable and
updated information and advice they need to determine the best treatment plan for their specific disease.
It is for these reasons that PCRI was established - to educate patients who, sadly, more often than not,
rush to treatments that affect their quality of life permanently. PCRI provides cutting-edge, unbiased,
and relevant information to its constituency either through its phone-based HELPLINE, quarterly Insights
newsletter, www.PCRI.org website and the annual national prostate cancer Conferences. And as most
of you know, PCRI provides educational brochures, videos/DVDs, books for practically no-cost to patients,
support groups and healthcare providers across the world.
Thanks to your friendship and support in years past – PCRI has continued to provide consistent and
reliable public service. But we ask that you help us with a generous donation so that we may continue to
be a valuable instrument to those who are and will be diagnosed with this dreadful disease. We appreciate
your support either through a one-time donation, a recurring donation or by including PCRI in your plannedgiving efforts. Know that your contribution helps us win the fight against prostate cancer!
As a token of our gratitude for your generosity, we will send you a copy of the highly successful 2010
Prostate Cancer Conference DVD for donations greater than $149. Please see details in the enclosed coupon.
Chester Swenson
President, PCRI Board
New Developments in Prostate Cancer Treatment
Prostate Cancer Research Institute is a 501 (c) (3) not-for-profit public charity
www.PCRI.org • PCRI Insights
Highlights of the Presentations
By: Jim O’Hara – PCRI Educational Facilitator
Key topics in the talks were amplified in Dr.
Moyad’s short Q&A exchange following each talk. One
attendee commented: “Questions by Moyad were
outstanding! Greatly expanding my understanding”.
While most of the questions explored deeper into new
concepts presented, one example I noted is that we
learned from Dr. Myers where his nickname “Snuffy”
Following each talk, the speaker adjourned to a
corner of the Exhibit Hall to answer questions from
interested attendees. This year, we recorded these
“Meet the Speakers” sessions and over 3 hours of
Q&A will be available on the conference DVDs.
Saturday’s Gala Dinner featured:
• A keynote talk by Dr. Mark Moyad (see
Lifestyle Modification below)
• The presentation of the Harry Pinchot
Awards and the Catalyst Award (see
separate article)
• An inspirational vocal presentation by
“America’s Tenor” Steve Amerson
Sunday, Dr. Mark Scholz began the program with
a recap of key topics from Saturday’s program. This
was followed by six breakout sessions for Q&A with
a number of experts that allowed direct interaction
for attendees. Comments indicated that more of this
type of session would be appreciated. Unfortunately,
these simultaneous sessions could not be recorded
for the DVDs. The conference concluded with a panel
discussion involving many of the speakers sharing
opinions relating to questions submitted from the
In addition to the educational sessions, many
attendees took part in: the four support groups during
lunch on Saturday; the “Women Against Prostate
Cancer” Breakfast meeting on Sunday; the two Los
Angeles Excursions and many casual opportunities
to share feelings with others facing similar concerns.
Attendees also took advantage of the wealth of
PCRI Insights • www.PCRI.org
information available from the conference supporters
in the Exhibit Hall. You can’t get these experiences from
the DVDs. To demonstrate the value some individuals
place on attending the conference, I spoke with one
man on Friday afternoon. He had just gotten off a plane
from the Netherlands. He told me he was returning
home after Sunday’s session.
The information content from over 20 hours of
presentations and Q&A sessions is enormous. I will not
try to summarize each talk in this article. The DVDs will
provide an opportunity for those interested to grasp the
content. I will report some of the key comments made
by the speakers that relate to several general topics
covered. Please refer to prior issues of PCRI Insights or
to the website for the agenda and a list of the faculty.
Lifestyle Modification
Both Drs. Ornish and Moyad cited the EPIC study
(European Prospective Investigation into Cancer and
Nutrition) published in 2008 for demonstrating the
importance of healthy lifestyle. Exercise, not smoking,
eating healthy and healthy weight (waist size) had
prevention benefits for Diabetes 93%, heart attacks
81%, strokes 50% and all cancers 36%.
Dr. Ornish suggested an optimal diet as low in animal
fats but also low in refined carbohydrates. He suggested
supplements of Vitamin D3 and fish oil. He mentioned
that fiber and bran can fill you up before eating too
many calories. Dr. Moyad suggested chia seeds as a
good source of fiber and omega-3.
Dr. Myers put special emphasis on this by saying
that to optimize your treatment outcome “You must
do your part!” He mentioned the importance diet
and exercise to improve blood pressure, cholesterol
and glucose levels. Patients should seek medications
to control these if lifestyle changes are not sufficient.
He also called for patients to maintain reasonable
optimism, to avoid pessimistic physicians and to
cultivate a “reason to live”.
In addition to monitoring cholesterol, Dr. Moyad
suggested hs-CRP (High-sensitivity C-reactive protein)
test be done with each cholesterol test. Less than 1
mg/L is considered low risk.
In his Active Surveillance talk, Dr. Strum emphasized
the importance of life style monitoring and
modification. In answer to a follow-up question from
Dr. Moyad, he replied that he felt the most important
(non-drug) factor is to restrict carbohydrates.
Active Surveillance
Dr. Strum said the major credit for the current emphasis
on Active Surveillance goes to Laurence Klotz MD in
Canada. Dr. Klotz has a 450 patient study with average
follow-up 6.8 years, an overall survival 78.6% and a 10year prostate cancer actuarial survival 97%.
As of 2009, 6 active surveillance studies published all
rely on PSA-kinetics and on rebiopsy findings.
When asked if endorectal MRI was better than
color Doppler ultrasound for monitoring A/S, he said
each has value and may identify problems that the
other does not. His advice, select an expert.
The following were comments by panel members to
a question about using just PSA to monitor A/S.
• If there happens to be aggressive cancer
present, PSA from prostate cancer may not
be a large % of total PSA – a prostatic acid
phosphatase PAP test may be beneficial
• Additional analysis of the biopsy samples using
Aureon Prostate Px+ may be useful – also, Dr.
Bonkhoff in Germany can produce a panel of 12
immunohistochemical tests to help determine
the nature of the cancer
Staging Prostate Cancer
Dr. Strum described the evolution of our imaging
tools. These have allowed for better staging and
the concept of delayed treatment. There was a
major setback with the FDA rejection of CombidexВ®.
Several speakers mentioned the value of Combidex
imaging done in the Netherlands for their patients.
Unfortunately, the manufacturer has discontinued the
product but a new product, ferumoxytol, is approved
for iron deficiency. Dr. Roach said he expected UCSF
would initiate a clinical trial using this with MRI in 2011.
• Total patients = 2,168
• Over 200 patients have > 10 years follow up
• Overall survival 93%
• CSS (cancer specific survival) 99.7%
Dr. Strum suggests additional testing be considered for men on Active Surveillance including:
• Color Doppler Ultrasound
• MRI & MR Spectroscopy
• DRE with formal report of findings including
capsule and seminal vesicles
• Biomarkers PAP, CGA, NSE & CEA
• Bone Integrity
Reprinted with permission of Dr. Strum
(Continued on page 26)
www.PCRI.org • PCRI Insights
Local Treatment
Dr. Gil answered a question saying
that there should not be a risk of
lymphedema after prostatectomy
because the lymph nodes removed
are not the ones that drain from the
Dr. Roach discussed “whole
pelvic radiation” for selected highrisk patients. He said that 42% of
the pelvic lymph nodes at risk are
outside the area that a surgeon
samples. He quoted research that
suggests an improvement of progression free survival by 2 years
without statistically significant increase in grade 3 toxicities.
He suggested that temporary implants might be better than permanent if the prostate is large or the
tumor extends beyond the capsule.
When asked by Dr. Moyad if
long-term ADT is required for highrisk patients, Dr. Roach replied that
2 years is the shortest duration of
ADT that has shown a survival benefit in random clinical trials.
When asked about stereotactic
radiation (like CyberknifeВ®), he
expressed concern that the higher
dose fractions might cause longterm risk of urethral strictures. He
said longer follow-up was needed
but questioned “Why choose this
when there is 20 year data for
When asked to compare proton
with IMRT, Dr. Roach said there is
no reason to believe that proton is
better if the dose is the same, also
there is no good data that side-effects are less. To a similar question,
Dr. Botnick said that image guidance and dose make the difference.
PCRI Insights • www.PCRI.org
The following were comments
to a panel question about high intensity focused ultrasound (HIFU)
•Potency outcomes about
60% – not as good as
•If prior prostatitis caused
calcification, ultrasound is
reflected leaving untreated
Radical prostatectomy, radiation and cryotherapy can all lead
to erectile dysfunction. Dr. Mulhall
discussed the four main factors that
contribute to this condition: cavernous nerve injury, artery injury,
erectile tissue damage and confidence erosion. He discussed several
ways to address these factors. He
stressed the importance of penile
rehabilitation after local treatment
for prostate cancer to preserve
erectile tissue while normal erections are not occurring. Loss of
erectile tissue leads to venous leak
and permanent function loss.
Dr. Mulhall discussed the risks
of damage to erection tissue
when testosterone is reduced. It
appears that 4-6 months of ADT
is enough to cause irreversible
erectile damage. He suggests
Вј pill of ViagraВ® at night (as
frequently as patient can afford)
while on intermittent ADT.
Dr. Strum emphasized the
importance of stopping the cycle
of bone loss with exercise, diet,
vitamin D3, boron, calcium and
bisphosphonates (if necessary).
Castration-Resistant Prostate
Cancer (CRPC)
Dr. Vogelzang stated that 30,000
develop CRPC each year in this
Dr. Myers and Dr. Vogelzang both
commented that patients should
not start chemotherapy until all
hormonal treatments (and possibly
Provenge) have failed unless there
is evidence of extremely aggressive
or extensive metastatic cancer.
Androgen Deprivation Therapy (ADT)
Dr. Myers commented that his goal
with ADT is to drive the PSA to
< 0.01 as quickly as possible and
continue for 12 months. If he is not
successful with the usual one to
three drugs, he moves directly to
second line with combinations of
ketoconazole or estrogens. During
off-cycles, he suggests options that
could increase PSA Doubling Time
like Proscar and Avodart, a Mediterranean diet, Celebrex (if medically
appropriate), vitamin D3, pomegranate, resveratrol, curcumin. He
cautioned when using supplements,
it is important to monitor for blood
levels and potential side-effects or
drug interactions.
Dr. Myers updated his results
with second-line hormonal therapy
using ketoconazole, Leukine and
estradiol. He reported a “75%
reduction in PSA was seen in 78%
of his patients with 49% reaching
an undetectable PSA. The bad and
good news: After 5 years, it is too
early to measure the full benefit.”
Dr. Moyad asked why a patient
should consider docetaxel when
the overall survival advantage is
just 2.5 months. Dr. Vogelzang
answered that despite the chemo
side-effects, quality of life was
better and some have much longer
survival. Dr. Scholz expanded on
this in his summary showing that a
30% PSA decline within 3 months powerfully predicts
improved survival. PSA response does not matter to the
FDA (even though it is obviously predictive of survival).
However, for guiding individual treatment decisions,
PSA response is extremely useful. In the TaxotereВ®
trials, the patients whose PSA normalized (less than
4.0) had a huge survival advantage over those that did
not. (see slide)
Reprinted with permission of Dr. Scholz
Dr. Scholz also commented that there are keys to
the management of CRPC patients which includes the
need to monitor response to treatment closely and if a
treatment is not working, move on to something else.
• Monitor for at least 60-90 days
– PSA, PAP, LDH, ALP tests monthly
PCRI Thanks Supporters and Volunteers
PCRI and all of the conference attendees are especially
indebted to the many supporters and volunteers who
helped to make the 2010 Prostate Cancer Conference
possible. These include:
Abbott Laboratories
Aureon Laboratories, Inc.
Bristol-Myers Squibb
Calypso Medical Technologies
Daily News Los Angeles
Dendreon Corporation
Eigen, Inc.
Ferring Pharmaceuticals, Inc.
Firma Medical, Inc.
Foundation for Cancer Research &
Education (FCRE)
Genentech, Inc.
Gen-Probe Inc.
GTx, Inc.
HealthTronics, Inc.
Hitachi, Ltd.
iCAD, Inc.
Life Extension Foundation
Mogreet, Inc.
Novartis Oncology
Optimum Health Institute
Patient Advocate Foundation
POM Wonderful, LLC
Prostate Institute of America
Prostate Oncology Specialists
Radnet Inc. Rolling Oaks Radiology
– Pain
• Check for the “Small Cell” variant
– Check CEA, NSE, CGA every 6 months
• Quality of life
– Monitor side effects from treatment
– Maintain fitness, diet and attitude (no
Dr. Lam discussed some of the side-effects and
stated that the most important concept is to take a
break as soon as it is safe. Dr. Moyad mentioned a trial
that suggests a benefit in taking ginger before Chemo
to reduce nausea.
Non-Profit Supporters
Patient Advocates for Advanced
Cancer Treatments (PAACT)
Us TOO International
Women Against Prostate Cancer
Linda Ball
Eileen Call
Joan Each
Hal Goodman
Inge Jones
Lynn Lively
William Mitchell
Robert Mohle
Jeremy Scholz
Harley Van DeLoo
Support Group Leaders
Bob Each
David and Kathie Houchens
Mark Lichty
Joel Nowak
Erlinda Patterson
Finally, Thanks to the 67 attendees who made generous
contributions in addition to their conference fees.
– Circulating Tumor Cells (CTC) monthly
– Bone scans, PET, CT, MRI (every 6 months?)
Theragenics Corporation
Valley Radiotherapy Associates
Vantage Oncology, Inc.
Update on Clinical Trials
Dr. Vogelzang reviewed the results of several recent and
ongoing trials.
CALGB 90401:
• Addition of bevacizumab (Avastin®) to
docetaxel/prednisone/ dexamethasone did
not significantly increase overall survival for
patients with CRPC
• Bevacizumab did significantly improve other
clinical outcomes
– Progression free survival, PSA decline,
incidence of measurable disease
• Bevacizumab treatment was associated with
more severe toxicities, including death from
(Continued on page 28)
www.PCRI.org • PCRI Insights
• Calcitriol plus weekly docetaxel associated
with significantly shorter survival times vs q3w
docetaxel in patients with metastatic CRPC
Based on similarity of survival times to
other studies of weekly docetaxel, survival
effect may be due to weekly docetaxel
schedule rather than to addition of calcitriol
• Neither protective effect nor reduced toxicity
observed with calcitriol plus weekly docetaxel
• Weekly docetaxel is not recommended
• Cabazitaxel (Jevtana®) was approved by FDA
6/17/10 in combination with prednisone for
patients with hormone-refractory prostate
cancer previously treated with docetaxel
• Cabazitaxel/prednisone (CP) significantly
improved overall survival vs. mitoxantrone/
prednisone (MP) in metastatic CRPC
• Reduced risk of death: 28%
• CP also significantly improved Progression free
survival, response rates, and time to progression
• Associated with acceptable safety profile
– Febrile neutropenia and diarrhea more
common with CP vs MP
• CP first treatment to demonstrate survival
benefit in patients with metastatic CRPC who
failed docetaxel-based therapy
• High incidence of adverse events in both arms
– More patients who received zoledronic acid
experienced acute phase reaction
– More patients who received denosumab
experienced hypocalcemia
– Osteonecrosis of the jaw rare but occurred
in approximately twice as many patients
with denosumab vs zoledronic acid
• Denosumab potential treatment option for
patients with CRPC and bone metastases
Several speakers discussed the FDA approval of
ProvengeВ® and its availability. Dr. Moyad discussed
the current controversy about a delay in approval
for payment by Medicare. A petition was circulated
to present to the Centers for Medicare & Medicaid
Services meeting on November 17th.
Dr. Bahn reviewed the “CRITICAL” trial for combined
cryotherapy and immunotherapy which is now in process. The FDA approval for the trial is for men who:
have proven recurrent cancer in the prostate after organ
preserving therapy; are determined to be androgen –independent; with known metastasis limited to three sites
and are chemo-naГЇve. The trial consists of cryoablation of
the prostate, followed by injection of a known number of
patients’ own immature dendritic cells into the cryoablated prostate with pre-and post-cryoablation low dose
cyclophosphamide administration to reduce regulatory
T cells temporarily. It is too early to report any findings.
• Warnings/precautions:
– Neutropenic deaths and mortality related to
gastrointestinal symptoms and renal failure
– Elderly (≥ 65 years) at increased risk of toxicity
– Not recommended if hepatic impairment present
Denosumab vs Zoledronic Acid:
• Denosumab superior to zoledronic acid
in delaying or preventing skeletal related
events (SRE) in patients with CRPC and bone
• No significant difference between treatments in
survival or disease progression
PCRI Insights • www.PCRI.org
Reprinted with permission of Dr. Bahn
Future Developments
The future looks brighter for prostate cancer patients.
With the 2010 approvals of sipuleucel-t and cabazitaxel,
physicians have two new weapons against the disease.
Dr. Vogelzang expressed optimism for the
approval of abiraterone based on a recent news
release stating that the Phase III study had been
“unblinded” because “based on a pre-specified
interim analysis, which demonstrated a statistically
significant improvement in overall survival and an
acceptable safety profile”. Based on these results,
it was recommended that patients in the placebo
arm be offered treatment with abiraterone acetate.
Additionally, a program will provide early access to
abiraterone acetate to patients who meet specified
medical criteria is being initiated. [The study is not
recruiting at the time of this writing but is listed as
NCT01217697 at www.clinicaltrials.gov].
Dr. Vogelzang commented that prostate cancer now
has two approved chemotherapies that have demonstrated improved survival. Breast cancer has five. He is
enthusiastic about ten other agents are in Phase III trials
(see slide). He stated that men must participate in the
trials. The higher level of participation by breast cancer
patients is one reason for higher funding to breast cancer trials and the larger number of approved treatments.
also described exciting PCF sponsored research at the
University of Michigan that has identified 24 types
of prostate cancer. This research may provide more
effective screening for identifying the men who would
likely benefit from treatment and additional ways
to define targets for treatments. He also described
research at UCLA that has identified four events that
occur to turn a prostate cell into a prostate cancer
stem cell. Other reasons for hope included the
extended survival provided by the new treatments
mentioned above and the many brilliant, young
investigators dedicated to prostate cancer research.
His final reason is the growing patient participation
as evidenced by the attendance at the 2010 Prostate
Cancer Conference.
The Multi-Disc DVD Set of the 2010 PROSTATE
CANCER CONFERENCE is expected to ship on
December 14th. See coupon for details.
(Continued from Page 2, Blue September)
The campaign has been a story of success
after success, with buildings including the iconic
Capitol Records Building, the Ramada Hotel in West
Hollywood, the historic Roosevelt Hotel and the
Paramount Studio’s Melrose Gate and Water Tower,
all bathed in blue light throughout the month.
Other key partners to jump on board early include
the Oakland Raiders, who dedicated their home
season opener to the campaign, and Messenger
Wines, who donated proceeds from their biggest
selling wine towards the cause.
The philosophy behind Blue September is one
of positivity and empowerment, using much loved
famous faces, looking a little ridiculous in blue paint,
and familiar landmarks, with a fun new �blue’ spin, to
reach as many people as possible. But the message
about prostate cancer is a serious one, with sobering
statistics. Prostate cancer affects over 2 million
Americans and is chronically underrepresented.
Reprinted with permission of Dr. Vogelzang
Dr. Jonathan Simons of Prostate Cancer Foundation
closed Saturday’s lecture session with a talk titled
“Scientific Progress: Top Ten Reasons for Hope”. He
listed 23 additional new agents in the pipeline. He
Ultimately, Blue September is about changing
America’s attitudes and behaviors towards prostate
cancer to save lives. For too long the issue has
gone unattended, and together the PCRI and Blue
September are going to change the face of prostate
cancer in America.
www.PCRI.org • PCRI Insights
PCRI Insights, November 2010, Vol 13: No 4
At the 2010 PCRI Conference Gala Dinner, PCRI was proud to present
awards to three individuals who have given of their time, talents and resources
to advance the mission of prostate cancer education and research
Har ry P i nc hot
Awa r d
In honor of the late Harry Pinchot, the Prostate Cancer Research Institute began awarding the Harry Pinchot
Award in 2008. Harry Pinchot is best remembered for his extensive knowledge of the biology, prevention, and
treatment of prostate cancer. Since his diagnosis in 1995, Harry impacted many patients and their caregivers
afflicted by prostate cancer simply with his knowledge and warm spirit. Harry served as PCRI’s Program
Director for over a decade, and was known as “Helpline Harry” because of the large number of calls he took
from prostate cancer patients. Harry lost his 12 year battle with prostate cancer in January 2008. In his honor,
PCRI recognizes unsung heroes who, like Harry, are making a difference in other people’s lives.
Men and women can be nominated based on their personal attributes and accomplishments in the fight
against prostate cancer through education, research, advocacy, and community support. When we looked
at the candidates for this 2010 Harry Pinchot Award, we were aware that two individuals stood out for
special commendation – both very worthy of the honor. PCRI is proud to present 2010 Harry Pinchot
Awards to Johnny Payne and Howard Hansen.
Johnny Payne has been described as a visionary, an activist, a motivator, a mentor, and an inspirer. He is a
prostate cancer survivor, a listener – one who “has been there”.
He learned (and continues to learn) all there is to know about prostate cancer and uses that to help African
American and all other men with prostate cancer. He is responsible for coordinating screening of over 1000
men annually, and giving more than 30 seminars that reach over 1500 men annually. He formed collaborations
PCRI Insights • www.PCRI.org
with health systems
and hospitals; with
Us TOO, American
Cancer Society, Zero
and the South Carolina
Cancer Alliance; with
men’s fraternities and
over 100 churches
in his area. He has
spread the word across
local media and has
earned several prestigious awards, including WJMZ
Black History Maker, Omega Psi Phi Organization of
the Year, and the Us TOO Edward Kaps Hope Award.
If that isn’t enough, he is founder and Executive
Director of Upstate Prostate Cancer Alliance.
In accepting the award, he said: “— the mission
is to make a difference – we want to put pressure
on our legislators to pass favorable legislation
so we can get funding to defeat this disease, find
a cure and if not necessarily a cure, find a better
screening method… that perhaps will end this “To
screen or not to screen” controversy.”
Bruce Laumeister,
HRPCa treasurer,
accepted the award
for Howard and
presented it to him at
his home in Vermont.
Howard Hansen is the co founder of the Hormone
Refractory Prostate Cancer Association (www.hrpca.
org) and has been helping patients with their disease
for 16 plus years. Using his advanced web site and
his extensive research into many medical journals, he
has given advice, assistance, and encouragement to
hundreds of patients with the more severe hormone
refractory prostate cancer. Howard’s compendium of
treatment options is available on his web site and is
constantly updated.
(Continued on page 32)
How to Contribute to PCRI
Direct Donations
Cash, check, or credit card; stock or
real estate.
Honor a loved one with a memorial
or commemorative gift in their name.
Payroll Deductions
Federal employees can contribute to the
Combined Federal Campaign in their
workplace. Look in the Cancer Cures
section of the CFC directory orc all PCRI for
the number.
Planned Giving
Naming PCRI in your will or as beneficiary
of your IRA or life insurance policy.
Planned Giving
For information on Planned Giving
opportunities or how to put PCRI
in your will, please contact PCRI
at (310) 743-2116, or by e-mail at:
[email protected]
Please Donate Today
Your tax-deductible gift of
cash,stocks or real estate, as well as
Gifts in Honor and Memorial Gifts,
should be made payable to PCRI
and mailed to:
Prostate Cancer
Research Institute
Gifts in Honor and
5777 W. Century Blvd Suite 800
Los Angeles, CA 90045
A gift to the PCRI is a special way to give
tribute allowing individuals, organizations,
businesses and groups to honor someone
while supporting PCRI’s mission.
Credit card donations can be
made at www.pcri.org or by
calling (310) 743-2116.
www.PCRI.org • PCRI Insights
A diagnosis of HRPC is a serious development
for the family fighting prostate cancer. It often comes
accompanied by an uncertain prognosis that adds an
emotional burden. Hansen and all of the volunteers
working on the HRPCA Web site have been through
this experience. Without exception, they have chosen
to reject defeat and to fight this disease with their time,
their ingenuity, their resources, and their computers.
Even when suffering from severe metastatic prostate
disease, Howard continued to be available for the
many men in the Hormone Refractory Prostate Cancer
web group. Howard’s stamina and endless assistance
to others is an inspiration to us all. He acquired the
nickname of “Helping Howard”.
In an emotional acceptance speech, Howard’s
friend Bruce Laumeister emphasized:
“- his incredible ability to translate this incredible
information into things to guide people as to what
to do next … this man has saved so many people
all over the world”
(Editor’s note: Unfortunately, we received word on
October 5th that Howard had lost his battle with prostate
cancer. Howard joins Harry Pinchot, 2008 award winner
Bill Blair and several others in memory as those who
unselfishly helped so many of us in this battle.)
he PCRI Catalyst Award
was established to highlight
the outstanding work and
generosity of individuals and
organizations that set the standards
for bettering the lives of those with
prostate cancer and their families.
The recipient is chosen by the
PCRI Board of Directors, and is
a person that PCRI considers “ an
agent of change” who has shown a
history of leadership, philanthropic
involvement and educational
commitment within the field of
prostate cancer. PCRI is thrilled to
present the second annual Catalyst
Award to James R. Warren II.
James R. Warren II is recognized
for his generosity in providing
financial resources that support and
strengthen prostate cancer education
and exciting research. His support
could potentially help millions of
men by inhibiting or treating prostate
cancer and that could significantly
improve patients’ quality of life.
PCRI Insights • www.PCRI.org
James Warren was raised in San
Diego, California and currently resides
in Kailua, Hawaii with his wife Michele.
He graduated from the University of
California, Santa Barbara in 1976 with a
B.S. degree in Biological Sciences, and is
also an alumnus of the Harvard Business
School. In 1978, he became a Founding
Partner of Kinko’s Copies and served as
the company President for ten years. He
currently serves on the Board of Trustees
for the University of California at Santa
Barbara Foundation. James enjoys
traveling, cooking, tennis, body surfing
and spending time with his children.
James Warren could not attend the
conference but in a video acceptance,
he stated: I would like to take this
opportunity to thank the dedicated
doctors and healthcare professionals
involved with this conference. … These
conferences have provided me with lots
of information and I have always been
impressed with the knowledge of the
attendees so I look forward to attending
next year’s conference and I hope
everyone considers supporting PCRI.”