EUROPEAN UROLOGY 69 (2016) 576–581
available at www.sciencedirect.com
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Platinum Priority – Prostate Cancer
Editorial by Peter C. Albertsen on pp. 582–583 of this issue
Pathologic Outcomes in Favorable-risk Prostate Cancer:
Comparative Analysis of Men Electing Active Surveillance and
Immediate Surgery
Jeffrey J. Tosoian a, Debasish Sundi a, Bruce J. Trock a,b,c, Patricia Landis a, Jonathan I. Epstein a,c,d,
Edward M. Schaeffer a,c,d, H. Ballentine Carter a,c, Mufaddal Mamawala a,*
a
The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA;
b
Department of Epidemiology, Johns Hopkins
Bloomberg School of Public Health, Baltimore, MD, USA; c Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; d Department
of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Article info
Abstract
Article history:
Accepted September 21, 2015
Background: It remains unclear whether men selecting active surveillance (AS) are at
increased risk of unfavorable longer term outcomes as compared with men who undergo
immediate treatment.
Objective: To compare adverse pathologic outcomes in men with favorable-risk prostate
cancer who underwent delayed prostatectomy after surveillance (DPAS) to those who
elected immediate prostatectomy (IRP).
Design, setting, and participants: We conducted a retrospective analysis of a prospective
AS registry from 2004 to 2014. From the Johns Hopkins AS program (n = 1298), we
identified a subset of men who underwent DPAS (n = 89) and was representative of
the entire cohort, not just those that were reclassified to higher risk. These men were
compared with men who underwent IRP (n =3788).
Outcome measurements and statistical analysis: We measured adverse pathologic
features (primary Gleason pattern 4, seminal vesicle invasion [SVI], or lymph node
[LN] positivity). Multivariable models were adjusted for age, prostate-specific antigen
density, and baseline risk classification.
Results and limitations: Delayed prostatectomy occurred at a median of 2.0 yr (range:
0.6–9.0) after diagnosis. The DPAS and IRP cohorts demonstrated similar proportions of
men with primary Gleason pattern 4 (17% vs 20%; p = 0.11), SVI (3.3% vs 3.2%; p = 0.53),
LN positivity (2.3% vs 1.2%; p = 0.37), and overall adverse pathologic features (21.3% vs
17.0%; p = 0.32). The adjusted odds ratio of adverse pathology was 1.33 (95% confidence
interval, 0.82–2.79; p = 0.13) for DPAS as compared with IRP. Limitations include a
modest cohort size and a limited number of events.
Conclusions: In men with favorable-risk cancer, the decision to undergo AS is not
independently associated with adverse pathologic outcomes.
Patient summary: This report compares men with favorable-risk prostate cancer who
elected active surveillance with those who underwent immediate surgery accounting
for evidence that approximately one-third of men who choose surveillance will eventually undergo treatment. Our findings suggest that men who are closely followed with
surveillance may have similar outcomes to men who elect immediate surgery, but
additional research is needed.
# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Associate Editor:
James Catto
Keywords:
Active surveillance
Oncologic outcomes
Prostate cancer
* Corresponding author. The James Buchanan Brady Urological Institute, 600 N. Wolfe Street, Park
200B, Baltimore, MD 21287, USA. Tel. +1 410 614 3724; Fax: +1 410 955 0833.
E-mail address: [email protected] (M. Mamawala).
http://dx.doi.org/10.1016/j.eururo.2015.09.032
0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY 69 (2016) 576–581
1.
Introduction
577
<0.15 ng/ml, biopsy Gleason score (GS) 6, two or fewer positive biopsy
cores, and 50% involvement of any core with cancer. We have not used
Curative intervention of prostate cancer (PCa) is associated
with side effects that are likely to have an impact on quality
of life [1,2]. Although morbidity may be accepted in the
setting of life-extending therapy, the treatment of indolent
nonlethal tumors exposes men to unnecessary negative
effects [3]. Despite improvements in diagnostic and imaging
techniques, it remains difficult to predict which cancers
will and will not prove harmful during a man’s lifetime
[4]. Active surveillance (AS) has been proposed as a
potential solution to this problem [5].
Although an increasing proportion of men are being
managed with AS [6,7], variability in utilizing this approach
is large and depends more on physician practice patterns
than tumor metrics [8]. One factor contributing to the
limited uptake of AS is a fear that failure to treat a localized
cancer while in a curable stage could prove costly over a
long-term follow-up [9]. The vast majority of favorable-risk
cancers demonstrate a prolonged, indolent course [10], but
approximately a third will eventually demonstrate higher
risk features [11]. In the absence of prospective trials
comparing various management strategies [12], previous
studies have compared surgical outcomes of men undergoing immediate radical prostatectomy (IRP) with subjects
initially managed on AS who subsequently underwent
delayed prostatectomy after an interval on surveillance
[13–15].
A major limitation of this approach, however, is that
most men on AS who proceed to surgery do so based on
worrisome findings such as biopsy reclassification or
increasing prostate-specific antigen (PSA) [15,16]. Thus
delayed radical prostatectomy (RP) cohorts have been
composed of the highest risk AS patients who ultimately
failed this approach. Although informative to this subgroup
of patients who fail AS during follow-up, such comparisons
provide minimal insight to the newly diagnosed man who
does not know whether he will later exhibit high-risk
disease. As such, others have proposed that an ideal study
design would compare an immediate surgery population
with a similar cohort that selected AS at the same time—
including both the minority of AS patients who progressed
to treatment and the majority of AS patients who remained
on surveillance [14]. Because this third group does not
undergo treatment, however, treatment outcomes are not
available for assessment. By incorporating a population of
men who elected to undergo treatment in the absence of
progression, however, we uniquely compared pathologic
outcomes from a risk-representative delayed surgery after
surveillance cohort with a similar cohort that underwent
IRP.
2.
Methods
2.1.
Active surveillance cohort
PSA (eg, >10 ng/ml) to exclude men from VLR classification if PSAD was
<0.15 because our experience has not identified a clinically meaningful
PSA cut-off to predict higher risk disease [18]. LR cancer was defined as
clinical stage T2a, PSA <10 ng/ml, and GS 6. Our protocol includes
semiannual PSA and digital rectal examination, and annual prostate
biopsy in most cases. As previously described, adherence to our protocol
approximates 90% annually [19]. Curative intervention is recommended
upon disease reclassification, defined as biopsy findings no longer
meeting inclusion criteria. Based on our experience, PSA kinetics are not
used as a trigger for intervention in this program [20]. As such,
interventions not due to biopsy reclassification are due to changes in
patient preference.
Of 1298 men enrolled in AS during the study period, 926 men (71.3%)
met VLR and 372 (28.7%) met LR classification criteria. During follow-up
(median: 5.0 yr; range: 0.01–18.0), 467 men (36.0%) underwent
reclassification at a median of 2.0 yr after diagnosis; conversely,
831 men (64% of the overall cohort) did not undergo reclassification and
were eligible to remain on AS. Of those who reclassified, 81 (6.5%)
reclassified based on grade, 234 (18.0%) reclassified based on volume,
and 149 (11.5%) reclassified based on grade and volume.
2.2.
Study design
We sought to assess an intermediate end point (ie, surgical pathology) in
the AS population for comparison with men who underwent immediate
treatment. Comparing the entire delayed RP population, however, with
men who undergo IRP is inherently biased against AS; the delayed RP
cohort does not represent all men who select AS, but rather those men
who select AS and then demonstrate higher risk disease during followup (Fig. 1). This bias has been described in the setting of AS by multiple
authors and is a well-recognized limitation of previous comparative
studies [14]. To mitigate this limitation, we aimed to identify a delayed
prostatectomy after surveillance (DPAS) population that represented the
overall AS cohort in terms of demographic factors, reclassification rate
during follow-up (36%), and type of reclassification observed (6.5% by
grade, 18% by volume, and 11.5% by grade and volume). To ensure
modern pathologic grading, the study was limited to men who
underwent surgery after 2004.
2.3.
Patient population
2.3.1.
Delayed prostatectomy after surveillance (study cohort)
From January 2005 to September 2014, a total of 185 men underwent
delayed prostatectomy after initial management on AS. Sixty-one men
elected to undergo RP in the absence of clinical or pathologic evidence of
disease progression. Four of these men (6.6%) were excluded due to age
(median age: 45.5 yr; range: 44–46 yr) discordant with the AS
population, yielding 57 study-eligible men who underwent delayed
RP without a trigger for intervention. Consistent with our AS experience,
these 57 men were designated to represent 64% of the DPAS study
cohort, and the total DPAS cohort was calculated to equal 89 subjects.
The study design is illustrated in Figure 2.
Corresponding to reclassification event rates in the overall AS
cohort, the remaining 36% (n = 32) of the DPAS study group was
composed of 6 men (6.7%) who underwent grade reclassification,
16 (18%) who underwent volume reclassification, and 10 (11.3%) who
underwent grade plus volume reclassification. To minimize selection
bias, subjects were selected from eligible men within each reclassification group using simple random sampling after stratification by year of
Starting in 1995, men with favorable-risk (ie, very low risk [VLR] or low
surgery. Patient characteristics were similar between the DPAS cohort
risk [LR]) PCa were offered enrollment in AS [17]. VLR criteria include
and overall AS cohort, confirming representative sampling (Supple-
clinical stage T1c disease, prostate-specific antigen density (PSAD)
mentary Table 1).
578
EUROPEAN UROLOGY 69 (2016) 576–581
[(Fig._1)TD$IG]
Nonreclassified
Acve
surveillance
Delayed
prostatectomy
Reclassified
Enriched with
higher risk
cancers
PCa diagnosis
Pathologic
outcomes
Immediate
prostatectomy
Fig. 1 – Schematic diagram of previous study designs. Traditionally, nonreclassified men do not undergo prostatectomy (dotted line), thus the active
surveillance (AS) population is represented mostly by men who failed a trial of surveillance based on evidence of progression. Outcomes in these men
do not accurately represent the overall AS population.
PCa = prostate cancer.
[(Fig._2)TD$IG]
Study Design
Johns Hopkins AS Program
(n = 1298)
AS Delayed Prostatectomy
Population (n = 185)
Nonreclassified
(n = 831)
64%
57 (64%)
Grade Reclassified
(n = 84)
6 (6.7%)
*
Nonreclassified
(n = 61)
+
6.5%
(SRS)
Grade Reclassified
(n = 31)
(SRS)
Volume Reclassified
(n = 55)
+
Volume Reclassified
(n = 234)
16 (18%)
18%
+
10 (11.3%)
Grade and
Volume Reclassified
(n = 149)
(SRS)
= 89
11.5%
Grade and
Volume Reclassified
(n = 38)
DPAS study cohort
Fig. 2 – Derivation of the delayed prostatectomy after surveillance (DPAS) study group. The DPAS study group was derived to model the overall active
surveillance cohort in terms of reclassification status (64% nonreclassified, 6.5% grade reclassified, 18% volume reclassified, 11.5% volume and grade
reclassified) and used simple random sampling stratified by year of surgery to select study subjects from the candidate pool. Subsequent analysis
confirmed that outcome rates were consistent with the source population (21% vs 19%; p = 0.75).
AS = active surveillance; DPAS = delayed prostatectomy after surveillance; SRS = simple random sampling.
2.3.2.
Immediate prostatectomy (control cohort)
(ie, primary Gleason pattern 4 or 5, seminal vesicle invasion [SVI], or LN
The IRP comparison group was composed of 3788 men who underwent
positivity) based on the association of this outcome with 15-yr PCa-
immediate prostatectomy for favorable-risk disease as diagnosed by a
specific mortality [22]. LN dissection is a provider-specific intervention
12-core biopsy; these data were obtained from a prospectively
at our institution; dissection was performed in 91% of patients assessed
collected institutional database [21]. IRP was defined as within 1 yr of
in this study cohort. Biochemical recurrence (BCR) was a secondary
diagnosis, although most patients underwent IRP within 4 mo (median
outcome defined as two consecutive PSA increases >0.2 ng/ml.
time to surgery: 3.0 mo; interquartile range [IQR]: 2.0–4.0 mo).
2.5.
2.4.
Statistical analysis
Outcomes
The DPAS and IRP cohorts were compared using the t test, Cochran t test,
The primary end points were pathologic features after RP including GS,
and chi-square analysis as appropriate. Unconditional multivariable
pathologic tumor stage, positive surgical margins, and lymph node (LN)
logistic regression was used to compare outcomes based on initial
positivity. Adverse pathology was considered as a composite outcome
treatment choice (ie, AS vs IRP). Factors significant on univariable
579
EUROPEAN UROLOGY 69 (2016) 576–581
Table 1 – Demographics of the study (delayed radical prostatectomy) and control (immediate radical prostatectomy) cohorts
DPAS cohort (n = 89)
Median
Range
Mean
SD
Median
Range
Mean
SD
p
65
2010
5.0
0.1
12
1
5
55–83
2005–2014
0.7–17
0.02–0.41
6–44
1–3
1–30
65.2
2010
5.4
0.12
13.5
1.5
8.3
3.5
3.4
2.6
0.08
6.8
0.7
7.7
58
2009
4.7
0.09
12
2
30
36–75
2005–2014
0.01–20
0.001–1.91
12–18
1–12
1–100
57.6
2009
5.3
0.1
12.4
2.9
35.3
6.6
3.0
2.8
0.07
2.8
2.1
27.9
<0.0001
0.16
0.50
0.04
0.1
<0.0001
<0.0001
Age at diagnosis, yr
Year of surgery
PSA, ng/ml
PSAD
Biopsy cores sampled, n
Cores positive for cancer, n
Maximum % involvement of any core with cancer
Risk classification
VLR
LR
IRP cohort (n = 3788)
n
%
n
%
p
63
26
70.8
29.2
1631
2157
43.1
56.9
<0.0001
DPAS = delayed prostatectomy after surveillance; IRP = immediate radical prostatectomy; LR = low risk; PSA = prostate-specific antigen; PSAD = prostatespecific antigen density; SD = standard deviation; VLR = very low risk.
Table 2 – Pathologic outcomes by study group
DPAS (n = 89)
Gleason score
3+3
3+4
4+3
4 + 4
Pathologic stage
pT2
pT3a
pT3b
Positive surgical margins
Lymph node positive
Adverse pathology*
IRP (n = 3788)
n
%
n
%
p
48
23
14
4
54.0
25.8
15.7
4.5
2410
840
416
122
63.6
22.2
11.0
3.2
0.26
71
15
3
12
2
19
79.8
16.9
3.3
13.5
2.3
21.3
3182
486
120
439
45
643
84.0
12.8
3.2
11.6
1.2
17.0
0.53
0.50
0.37
0.32
DPAS = delayed prostatectomy after surveillance; IRP = Immediate radical prostatectomy.
Primary Gleason pattern 4 or 5, seminal vesicle invasion, or lymph node positivity.
*
analysis were included in the multivariable model. To ensure stable and
valid results, we chose to limit the number of input variables by using
VLR/LR status in place of collinear variables used to define risk status
(ie, number of positive cores, maximum percentage involvement of any
core) [23]. The resultant odds of adverse pathology were unchanged in a
sensitivity analysis including the distinct variables (odds ratio [OR]:1.41;
95% confidence interval [CI], 0.73–2.66). BCR was assessed on survival
analysis and compared using the log-rank test. Post hoc power
estimation was performed using the Wald test, adjusting for confounders in the logistic model. All statistical analyses were performed
using SAS v.9.2 (SAS Institute, Cary, NC, USA) and were two sided;
p < 0.05 was considered statistically significant.
3.
Results
Men in the DPAS study cohort underwent RP at a median of
2.0 yr after diagnosis (IQR: 1.0–4.0 yr) as compared with
3.0 mo (IQR: 2.0–4.0 mo) in the comparison (IRP) cohort. As
demonstrated in Table 1, the DPAS cohort was older
(p < 0.001) and had higher PSAD (p = 0.04) than the IRP
cohort. The DPAS cohort had a lower mean number of cores
positive for cancer (1.5 vs 2.9; p < 0.001) and lower mean
percentage core involvement (8.3 vs 35.3; p < 0.001).
Accordingly, the DPAS cohort had a greater proportion of
men with VLR disease (70.8% vs 43.1%; p < 0.001).
Table 2 shows the pathologic outcomes. The DPAS cohort
demonstrated a nonsignificant trend toward higher GS
(p = 0.26). Positive surgical margins were observed in
12 men (13.5%) in the DPAS cohort and 439 (11.6%) in
the IRP cohort (p = 0.50); a positive LN was observed in 2.3%
of the DPAS cohort versus 1.2% of the IRP cohort (p = 0.37).
Ultimately, adverse pathology was present in 19 of 89 men
(21.3%) in the DPAS cohort and 643 of 3788 (17.0%) in the
IRP group (p = 0.32). In the multivariable model adjusted for
age, PSAD, and preoperative risk classification (ie, VLR/LR),
the OR for adverse pathology was 1.33 (95% CI, 0.82–2.79;
p = 0.13) in the DPAS cohort as compared with the IRP
cohort (Table 3). Post hoc power estimation using the Wald
test for logistic regression was 0.573.
Median follow-up for assessment of BCR was 2.0 yr in the
DPAS cohort and 3.0 yr in the IRP cohort. BCR was observed
in 6 men (6.7%) in the DPAS group and 160 (4.2%) in the IRP
cohort, and median interval to BCR was not reached in
either group. On survival analysis there was no significant
difference in time to BCR rate in the groups (p = 0.10).
580
EUROPEAN UROLOGY 69 (2016) 576–581
Table 3 – Multivariable analysis for adverse pathology
Univariable analysis
Delayed vs immediate
Age per year
PSAD per 0.1-unit increase
VLR vs LR
Multivariable analysis
OR (95% CI)
p
1.24 (0.80–2.05)
0.27
OR (95% CI)
1.33
1.06
1.22
0.64
(0.82–2.79)
(1.04–1.08)
(1.09–1.44)
(0.48–0.86)
p
0.13
<0.0001
<0.0001
0.003
CI = confidence interval; LR = low risk; OR = odds ratio; PSAD = prostate-specific antigen density; VLR = very low risk.
4.
Discussion
AS is one strategy to mitigate the overtreatment associated
with PSA-based screening. The absence of data comparing
men on AS with immediate treatment populations has
made it difficult to quantify the long-term risks associated
with choosing AS. We found that the likelihood of harboring
adverse pathology was not significantly different in men
with favorable-risk PCa who initially opted for AS versus
those who underwent IRP. Acknowledging that our outcome of interest was an intermediate pathologic end point,
these findings suggest that the decision to defer IRP for AS
may not compromise longer term outcomes in men willing
to undergo careful monitoring.
Delayed surgery cohorts in previous comparisons were
enriched with men who failed AS during follow-up.
Iremashvili et al examined 22 men who underwent DPAS,
of whom 16 (73%) demonstrated biopsy GS upgrading prior
to surgery and the remaining 6 (27%) underwent volume
reclassification [24]. In RP specimens, they observed a greater
proportion of primary GS 4 (32% vs 11%; p = 0.023) and a
higher median percentage of cancer (12.5% vs 5.0%; p = 0.009)
in the DPAS cohort as compared with the IRP cohort, although
there were similar rates of extraprostatic extension, SVI, LN
positivity, and positive margins. Satkunasivam and colleagues assessed a DPAS cohort of 41 men, of whom 68%
demonstrated biopsy GS upgrading, 12% demonstrated
volume reclassification, and 7% had a rapidly rising PSA
level prior to surgery [15]. The authors reported significantly
higher likelihood of GS 7 (65.9% vs 37.6%; p = 0.004), pT3
disease (36.6% vs 10.7%; p = 0.0002), and positive margins
(14.6% vs 1.8%; p = 0.007) in the DPAS cohort.
Certainly most studies suggest at least a trend toward
less favorable outcomes in this subgroup. Understanding
such risks is essential in counseling this population of men
who progress on AS, approximately a third of those
enrolling, regarding the probability of adverse outcomes
should they proceed to surgery. At the same time, it is
essential to recognize that these studies address a question
fundamentally different from ours, quantifying the risk
posed specifically to those men who enroll in AS and then
fail during follow-up. By comparison, our study sought to
assess the risk associated with initially choosing AS while
factoring in the likelihood that approximately a third of
such men will progress to treatment and acknowledging
our inability prospectively to identify which men will
progress [11]. Facing a decision between immediate
treatment and AS, our study provides insight for the newly
diagnosed patient who does not know whether he will
progress during monitoring and who would like to consider
his risk of negative longer term outcomes should he elect AS.
Acknowledging use of an intermediate end point,
selecting AS for initial management of favorable-risk
disease does not appear to predict unfavorable outcomes.
Certainly, as Filipou et al and others have demonstrated
[25], clinical findings during AS have a significant impact on
longer term outcomes. Given that contemporary techniques
cannot accurately predict which men will fail AS during
follow-up, the ability to characterize risk to all AS-eligible
men should prove helpful in counseling and decision
making. Discussing unfavorable outcomes after a trial on
AS is a difficult scenario, but evidence indicates that wellinformed patients are more engaged, more likely to fully
consider the risks and benefits of treatment options, and
more satisfied with clinical encounters [26]. These attributes are undeniably critical to shared decision making, and
such findings further emphasize the importance of discussing risks and benefits prior to proceeding with any
management strategy.
The current study was limited by a relatively small study
cohort, and it is possible that the observed trend toward more
frequent adverse outcomes in AS would reach statistical
significance in a larger population. Nonetheless, this study is
the first to our knowledge to use a risk-stratified cohort
corresponding to contemporary AS populations instead of
only the highest risk men, and our findings should prove
useful as a starting point in discussing AS. Because our
program utilizes conservative selection and monitoring
criteria, these results may differ in cohorts composed of
higher risk men and those with less stringent follow-up. Most
men were white, and our findings may not apply to more
racially diverse cohorts. At the same time, magnetic
resonance imaging was not formally included in our protocol
during the study period, and use of additional aids such as
imaging or genomic testing may have an impact on the
applicability of our findings. Finally, although well-validated
in multiple cohorts, the intermediate end points used in this
study may not completely reflect the outcomes most
important to patients such as freedom from PCa death and
metastasis.
5.
Conclusions
Our findings suggest that the decision to initiate AS of
favorable-risk PCa is not independently associated with
adverse pathologic findings. Observations during the course
EUROPEAN UROLOGY 69 (2016) 576–581
of surveillance certainly influence longer term outcomes,
and additional research is needed to better identify patientlevel factors most predictive of prognosis.
581
[9] Sandhu GS, Andriole GL. Active surveillance for prostate cancer:
barriers to widespread adoption. Eur Urol 2012;62:984–5.
[10] Popiolek M, Rider JR, Andren O, et al. Natural history of early,
localized prostate cancer: a final report from three decades of
Author contributions: Mufaddal Mamawala had full access to all the data
in the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Tosoian, Sundi, Trock, Epstein, Schaeffer, Carter,
Mamawala.
Acquisition of data: Mamawala.
Analysis and interpretation of data: Tosoian, Sundi, Trock, Carter,
Mamawala.
Drafting of the manuscript: Tosoian, Sundi, Carter, Mamawala.
Critical revision of the manuscript for important intellectual content:
Epstein, Schaeffer, Sundi.
Statistical analysis: Mamawala.
Obtaining funding: None.
Administrative, technical, or material support: Landis.
Supervision: None.
Other (specify): None.
Financial disclosures: Mufaddal Mamawala certifies that all conflicts of
follow-up. Eur Urol 2013;63:428–35.
[11] Dall’Era MA, Albertsen PC, Bangma C, et al. Active surveillance for
prostate cancer: a systematic review of the literature. Eur Urol
2012;62:976–83.
[12] Lane JA, Donovan JL, Davis M, et al. Active monitoring, radical
prostatectomy, or radiotherapy for localised prostate cancer: study
design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncol 2014;15:1109–18.
[13] Warlick C, Trock BJ, Landis P, Epstein JI, Carter HB. Delayed versus
immediate surgical intervention and prostate cancer outcome. J
Natl Cancer Inst 2006;98:355–7.
[14] van den Bergh RC, Steyerberg EW, Khatami A, et al. Is delayed
radical prostatectomy in men with low-risk screen-detected prostate cancer associated with a higher risk of unfavorable outcomes?
Cancer 2010;116:1281–90.
[15] Satkunasivam R, Kulkarni GS, Zlotta AR, et al. Pathological, oncologic and functional outcomes of radical prostatectomy following
active surveillance. J Urol 2013;190:91–5.
interest, including specific financial interests and relationships and
[16] Hussein AA, Welty CJ, Ameli N, et al. Untreated Gleason grade
affiliations relevant to the subject matter or materials discussed in the
progression on serial biopsies during prostate cancer active sur-
manuscript (eg, employment/affiliation, grants or funding, consultan-
veillance: clinical course and pathological outcomes. J Urol 2015;
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
194:85–90.
[17] Tosoian JJ, Mamawala M, Epstein JI, et al. Intermediate and
longer-term outcomes from a prospective active-surveillance
Funding/Support and role of the sponsor: None.
program for favorable-risk prostate cancer. J Clin Oncol 2015;
33:3379–85.
Appendix A. Supplementary data
[18] Umbehr MH, Platz EA, Peskoe SB, et al. Serum prostate-specific
antigen (PSA) concentration is positively associated with rate of
disease reclassification on subsequent active surveillance prostate
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
eururo.2015.09.032.
[19] Tosoian JJ, Trock BJ, Landis P, et al. Active surveillance program for
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