0022-5347/05/1743-0903/0
THE JOURNAL OF UROLOGY®
Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Reprinted from Vol. 174, 903–907, September 2005
Printed in U.S.A.
DOI: 10.1097/01.ju.0000169475.00949.78
DO MARGINS MATTER? THE PROGNOSTIC SIGNIFICANCE OF
POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY
SPECIMENS
PETER SWINDLE,* JAMES A. EASTHAM,†, ‡ MAKOTO OHORI,* MICHAEL W. KATTAN,*
THOMAS WHEELER,* NORIO MARU,* KEVIN SLAWIN§ AND PETER T. SCARDINO储
From the Department of Urology, Memorial Sloan-Kettering Cancer Center, Sidney Kimmel Center for Prostate and Urologic Cancer, New York, New
York (PS, JAE, MO, MWK, PTS), and the Departments of Urology and Pathology, Baylor College of Medicine, Houston, Texas (TW, NM, KS)
ABSTRACT
Purpose: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy
(RP) specimens remains unclear. While most studies have concluded that a PSM is an independent
adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One
reason for these discordant conclusions is the variable number of patients with a PSM who receive
adjuvant therapy and the differing statistical methods used to account for the effects of the time
course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using
multiple methods of analysis accounting for patients who received adjuvant therapy.
Materials and Methods: We analyzed 1,389 consecutive patients with clinical stage T1–3
prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM,
37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy.
Because the method used to account for men receiving AT can affect the outcome of the analysis,
data were analyzed by the Cox proportional hazards technique accounting for patients receiving
AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing
at time of AT and 5) considering AT as a time dependent covariate.
Results: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and
23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence
when analyzed using methods 1, 3, 4 and 5 (p⫽0.005, p⫽0.014, p⫽0.0005, p⫽0.002, respectively).
However, it was not a predictor of recurrence using method 2 in which AT was ignored (p⫽0.283).
Using method 5 multivariate analysis demonstrated that a PSM (p⫽0.002) was an independent
predictor of 10-year progression-free probability (PFP) along with Gleason score (p⫽0.0005),
extracapsular extension (p⫽0.0005), seminal vesicle invasion (p ⬍0.0005), positive lymph nodes
(p ⬍0.0005) and preoperative serum prostate specific antigen (p ⬍0.0001). Using method 5 the
10-year PFP was 58% ⫾ 12% and 81% ⫾ 3% for patients with and without a PSM, respectively
(p ⬍0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95%
confidence interval 1.06 –2.16).
Conclusions: We confirm that a PSM has a significant adverse impact on PFP after RP in
multivariate analysis using multiple statistical methods to account for patients who received AT.
While prostate cancer screening strategies have resulted in a majority of men having organ
confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical
margins to improve cancer control outcomes.
KEY WORDS: prostatectomy, prognosis, recurrence, treatment outcome
Recurrence of prostate cancer after radical prostatectomy
(RP) has been associated with multiple factors including
pretreatment serum prostate specific antigen (PSA), clinical
stage, biopsy Gleason grade, pathological stage (level of exSubmitted for publication August 9, 2004.
Supported by the Leon Lowenstein Foundation, the Bendhein
Prostate Diagnostic Center and a SPORE (CA92629) Grant from the
National Cancer Institute.
* Nothing to disclose.
† Correspondence: Department of Urology, Sidney Kimmel Center for
Prostate and Urologic Cancer, Memorial Sloan-Kettering Cancer Center,
353 East 68th St., Suite 527, New York, New York 10021 (telephone:
646-422-4390; FAX: 212-988-0759; e-mail: [email protected]).
‡ Financial interest and/or other relationship with Novartis.
§ Financial interest and/or other relationship with GlaxoSmithKline, National Institutes of Health, Merck, Urology, MedReviews
and Oncovance.
储 Financial interest and/or other relationship with Steba Pharmaceuticals, Oncovance Inc, Merck, Sanofi Aventis, National Cancer
Institute, National Institutes of Health, Prostate Cancer Foundation, Astra Zeneca, Pfizer, Nature Urology and Penguin Putnam Inc.
tracapsular extension, seminal vesicle invasion [SVI] and
pelvic lymph node status), and surgical margin status.1, 2 Of
these prognostic factors only surgical margin status can be
influenced by surgical technique.
A positive surgical margin (PSM) is defined as tumor at the
inked margin of the resected specimen.3, 4 A PSM can result
from incising into extraprostatic tumor in patients with extracapsular extension (ECE) or by inadvertent incision into
an otherwise organ confined cancer (pT2⫹).5 The reported
incidence of PSMs ranges from 6% to 41% and in general the
PSM rate in academic institutions has decreased during the
last 15 years.6⫺8 This decrease in PSM rate has likely resulted from a combination of stage migration with a larger
proportion of patients having clinical stage T1c disease and
Editor’s Note: This article is the first of 5 published in this
issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions
on pages 1160 and 1161.
S47
Please cite this article as J Urol 2008;179: S47–S51. DOI: 10.1016/j.juro.2008.03.137. Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION.
S48
POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS
pathologically organ confined cancer, and from improved surgical techniques.
Numerous studies report that a PSM adversely affects
prognosis after RP.3, 4, 9, 10 The 5-year biochemical failure
rate in patients with a PSM ranges from 42% to 64%.6 Despite these findings there is still controversy regarding the
clinical significance of PSMs on outcome.2, 11, 12 Using the
Cox proportional hazards model Stamey et al concluded that
a PSM was not independently predictive of biochemical failure following radical prostatectomy, although this study excluded men with transition zone cancers and the role/use of
adjuvant therapy in this study was not discussed.11 Furthermore, several studies that have assessed the significance of
positive margins excluded from the analysis patients who
received adjuvant therapy (AT), while other studies counted
those receiving AT as immediate treatment failures.2, 3, 13–15
Either of these methods of analysis creates the potential for
bias because the outcome for men receiving AT is unknown.
To address the impact of a PSM on biochemical recurrence
after RP more appropriately, we used multiple methods of
statistical analyses to account for the use of AT in a large
series of patients. To compare with previous reports assessing the impact of a positive surgical margin on patient outcome, we analyzed the data by the Cox proportional hazards
technique dealing with patients who received AT in 5 ways,
namely 1) exclusion, 2) inclusion (AT ignored), 3) censoring at
the time of AT, 4) failing at the time of AT and 5) considering
AT as a time dependent covariate. Moreover we examined
the significance of a PSM when other adverse factors were
considered by means of a multivariate analysis.
MATERIALS AND METHODS
Patient population. From August 1983 to September 2000,
1,389 consecutive patients with clinical stage T1-T3 prostate
cancer underwent radical prostatectomy by 2 surgeons (PTS
and KS) at Baylor College of Medicine. Mean patient age was
62 years (range 38 to 81). Overall 179 of the 1,389 patients
had a PSM (12.9%). Ten patients had no pathology slides
available for review and were excluded from analysis.
Pathology. Radical prostatectomy specimens were fixed intact in 10% neutral buffered formalin and then sectioned
transversely at 4 to 5 mm intervals. All specimens were
whole mounted and reviewed by 1 pathologist (TW). The
location and extent of cancer were identified and mapped in
each section. The presence of tumor cells at the inked margin
of resection was considered to represent a PSM.5 A positive
surgical margin in an area where no capsule was identified
was referred to as pT2⫹ and was thought to indicate where
the plane of dissection entered the prostatic capsule or alternatively where no capsule was present, ie apex and anteriorly.5 The presence and level of extracapsular extension,
Gleason grade, and PSM presence and sites were recorded.
Total tumor volume was measured from a tumor map using
image analysis software.16
Followup. The 1,389 patients were followed from 1 to 202
months with a median of 50 months (mean 52.3). Clinical
examination and serum PSA were performed every 3 months
during year 1, every 6 months during years 2 to 5 and yearly
thereafter. Biochemical recurrence was defined as a PSA
greater than 0.4 ng/ml confirmed on 1 subsequent PSA evaluation. The Hybritech® PSA assay was used for PSA followup. A total of 37 patients received adjuvant therapy before evidence of biochemical or clinical recurrence, 29
adjuvant radiation therapy (26 had a PSM) and 8 adjuvant
hormonal therapy (6 had a PSM).
Statistical analysis. We first analyzed AT as a time dependent covariate in a Cox model, adjusting for commonly available postoperative factors. For comparison we ran other models, variously excluding or including patients who received
AT. The probability of recurrence was analyzed by the Cox
proportional hazards technique first by excluding all patients
who received AT from analysis, then by including those who
received AT and ignoring the AT, then by censoring those
patients at the time of AT, and finally by considering AT as
treatment failure or recurrence. Categorical variables were
compared by the chi-square test. The ordinal and continuous
outcomes were compared with the Kruskal-Wallis or
Wilcoxon rank sum test. Progression-free probability was
calculated using the Kaplan-Meier method, and the differences between progression-free rates were assessed by the
log rank test. Cox proportional hazards regression analysis
was used to test association of various pathological and clinical features with recurrence. Logistic regression analysis
was used to evaluate the association between year of surgery
and PSM. Statistical analyses were performed with Stata®
version 7.0 or S-PLUS® version 6.1.
RESULTS
Clinicopathological parameters and margin status. Overall
179 of 1,389 patients had a PSM (12.9%). A PSM was identified
in 6.8% (58 of 847) of patients with organ confined disease
(pT2⫹) and in 23% (121 of 522) of patients with ECE (pT3).
Table 1 demonstrates the relationship between PSM and the
clinicopathological features. The incidence of PSM increases
with increasing preoperative serum PSA, Gleason score in the
RP specimen and pathological stage.
PSA progression-free probability. Figure 1 shows the PSA
progression-free probability (PFP) for all patients based on
the status of the surgical margins. Overall patients with a
PSM had a 10-year PFP of 58% ⫾ 12% compared with patients with negative surgical margins who had a 10-year PFP
of 81% ⫾ 3% (p ⬍0.00005). PSA progression-free probability
varied depending on how patients who received AT were
considered in the statistical analysis. Of the 37 patients
receiving AT, 10 subsequently had PSA recurrence and the
remaining 27 patients remained free of cancer recurrence
(median followup 93 months, range 12 to 160). Data were
analyzed using 5 methods and the results are displayed in
table 2. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p⫽0.005,
p⫽0.014, p⫽0.0005 and p⫽0.0021, respectively) but not
method 2 in which AT was ignored (p⫽0.283).
Multivariate analysis. Pretreatment serum PSA, Gleason
TABLE 1. Association of clinical and pathological features with
surgical margin status
No. Pts
PSA (ng/ml):*
0.1–4.0
4.1–10.0
10.1–20.0
Greater than 20.0
261
729
214
112
Total ⫹ SM
% (No.)
5.4
9.2
20.6
34.8
(14)
(67)
(44)
(39)
Total
RP Gleason score:†
2–6
7 (3⫹4)
7 (4⫹3)
8–10
1,316
12.5 (164)
981
247
70
77
10.9 (110)
12.1 (31)
18.6 (13)
33.3 (24)
Total
Clinical stage:
T1a
T1b
T1c
T2a
T2b
T2c
T3
1,375
12.9 (178)
35
53
491
262
322
150
76
Total
1,389
* No available PSA results for 73 patients.
† No available RP Gleason score results for 14 patients.
0
26.4
11.2
9.2
14.3
15.3
22.4
(14)
(55)
(24)
(46)
(23)
(17)
12.9 (179)
S49
POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS
organ confined cancer from 40% before 1990 to 78% after
2000. There has been a similar decrease in the PSM rate
especially in patients with pT3a or greater cancers, with the
margin rate decreasing from 31.7% before 1990 to 11.1%
after 2000. Using logistic regression analysis, year of surgery
(p⫽0.02) and presence of organ confined cancer (p⫽0.001)
contributed to the decrease in PSM incidence (fig. 4).
DISCUSSION
FIG. 1. PSA progression-free probability curves demonstrating
difference in outcomes for all patients with (⫹) and without (-)
positive surgical margin (SM) (p ⬍0.00005).
score in the radical prostatectomy specimen, presence of extracapsular extension, SVI and lymph node invasion (LNI)
were all found to be independent predictors of progression in
all 5 methods of analysis (table 3). A PSM was found to be a
significant predictor of progression for all methods of analysis except for method 2 (p⫽0.283), in which patients who
received AT were included in analysis and the effect of AT
was ignored. The relative risk of biochemical failure in men
with a PSM ranged from 1.2 to 2.7 depending on statistical
method. For patients with ECE (pT3a) a PSM was significant
using all statistical methods of examining patients who received AT (fig. 2, table 2). The significance of a PSM for
patients with organ confined tumors (pT2⫹) is less clear (fig.
3, table 2). Of the 5 methods only method 4, failing at AT,
indicated that a PSM was a statistically significant factor in
this group.
Variation in PSM rate over time. Figure 4 shows the variation in PSM rate over time in conjunction with the proportion of patients with or without organ confined cancer. There
has been a steady increase in the proportion of patients with
Our results suggest that cancer present at the margin of
resection (a positive surgical margin) in a radical prostatectomy specimen is associated with an increased risk of recurrence after adjusting for other known risk factors including
pretreatment serum PSA, clinical stage, Gleason score and
pathological stage (level of extracapsular extension, SVI and
pelvic lymph node status). A similar analysis has been previously performed on a larger cohort of patients (2,518) which
produced similar results.17 Of these prognostic factors only
the surgical margin status can be influenced by surgical
technique. Indeed in a recent analysis of risk factors for
positive margins, the volume of cases performed by the surgeon and the individual surgeon were each associated with
the risk of a positive margin after controlling for all other
clinical and pathological variables.18 In the present study we
found a decrease in PSM rate by year independent of the
favorable stage migration to more organ confined cancers
(fig. 4). Surgical experience and careful attention to surgical
details, adjusted for the characteristics of the cancer being
treated, can decrease PSM rates and improve cancer control
with radical prostatectomy.
Our overall PSM rate for the 18 years of study was 12.9%,
within the range of but substantially lower than the average
PSM rate reported in other series,3, 7, 8 with a reported
mean PSM rate of 25% to 28% and ranging from 6% to 41%.5
A PSM may occur as a result of incising into prostate cancer
that extends beyond the prostatic capsule (ECE and PSM)
and may also result from incising into intraprostatic tumor in
otherwise organ confined cancer (pT2⫹).5 Our PSM rate was
12.9% overall, 23% for patients with ECE and 6.8% for patients with organ confined disease compared to a mean in the
literature of 28% overall, 46.5% for patients with ECE and
TABLE 2. Impact of margin status on outcomes depending on the method of analysis
Mean ⫾ SD
No. pts
All pts:
5 Yrs
10 Yrs
⫹SM 5 yrs
⫹SM 10 yrs
⫺SM 5 yrs
⫺SM 10 yrs
p Value
pT2 (organ confined):
⫺SM 5 yrs
⫺SM 10 yrs
⫹SM 5 yrs
⫹SM 10 yrs
p Value
pT3a (ECE):
⫺SM 5 yrs
⫺SM 10 yrs
⫹SM 5 yrs
⫹SM 10 yrs
p Value
pT3b/⫹LN (SVI or LNI):
⫺SM 5 yrs
⫺SM 10 yrs
⫹SM 5 yrs
⫹SM 10 yrs
p Value
Method 1
Method 2
Method 3
Method 4
Method 5
1,352
1,389
1,389
1,389
1,389
82.6 ⫾ 2
78.9 ⫾ 3
62.4 ⫾ 10
58.3 ⫾ 10
85.0 ⫾ 2
81.4 ⫾ 3
⬍0.00005
82.3 ⫾ 2
78.0 ⫾ 3
65.6 ⫾ 8
58.0 ⫾ 12
84.9 ⫾ 2
81.4 ⫾ 3
⬍0.00005
82.6 ⫾ 2
79.0 ⫾ 3
63.5 ⫾ 10
59.4 ⫾ 10
85.0 ⫾ 2
81.4 ⫾ 3
⬍0.00005
80.2 ⫾ 2
76.7 ⫾ 3
50.5 ⫾ 8
47.2 ⫾ 10
84.6 ⫾ 2
81.1 ⫾ 3
⬍0.00005
82.3 ⫾ 2
78.0 ⫾ 3
65.6 ⫾ 8
58.0 ⫾ 12
84.9 ⫾ 2
81.4 ⫾ 3
⬍0.00005
93.9 ⫾ 2
92.1 ⫾ 2
91.6 ⫾ 10
80.5 ⫾ 16
0.1560
93.9 ⫾ 2
92.1 ⫾ 2
92.7 ⫾ 8
84.1 ⫾ 14
0.2761
93.9 ⫾ 2
92.1 ⫾ 2
91.8 ⫾ 10
80.6 ⫾ 16
0.1667
93.6 ⫾ 2
91.8 ⫾ 2
82.9 ⫾ 16
72.8 ⫾ 16
0.0001
93.9 ⫾ 2
92.1 ⫾ 2
92.7 ⫾ 8
84.1 ⫾ 14
0.2761
83.9 ⫾ 6
78.9 ⫾ 6
62.2 ⫾ 16
62.2 ⫾ 16
0.0046
83.9 ⫾ 6
78.9 ⫾ 6
64.3 ⫾ 14
60.7 ⫾ 16
0.0042
83.9 ⫾ 6
78.9 ⫾ 6
63.1 ⫾ 16
63.1 ⫾ 16
0.0071
83.9 ⫾ 6
78.9 ⫾ 6
51.0 ⫾ 14
51.0 ⫾ 14
⬍0.00005
83.9 ⫾ 6
78.9 ⫾ 6
64.3 ⫾ 14
60.7 ⫾ 16
0.0042
42.2 ⫾ 10
36.1 ⫾ 10
24.6 ⫾ 16
24.6 ⫾ 16
0.0521
42.8 ⫾ 10
36.7 ⫾ 10
40.5 ⫾ 14
27.0 ⫾ 24
0.7565
42.3 ⫾ 10
36.2 ⫾ 10
27.0 ⫾ 16
27.0 ⫾ 16
0.1408
41.2 ⫾ 10
35.2 ⫾ 10
17.0 ⫾ 12
17.0 ⫾ 12
0.0001
42.8 ⫾ 10
36.8 ⫾ 10
40.5 ⫾ 14
27.0 ⫾ 24
0.7565
S50
POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS
TABLE 3. Multivariate analysis of pathological risk factors for disease recurrence
p Value:
⫹SM
Gleason sum
ECE
SVI
⫹LN
PSA
AT
Hazard ratio for ⫹SM
95% CI
Method 1
Method 2
Method 3
Method 4
Method 5
0.005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
–
1.66
1.17–2.38
0.014
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
–
1.56
1.09–2.23
0.283
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.005
–
1.2
0.86–1.67
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.005
–
2.71
2.03–3.63
0.0021
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0005
⬍0.0001
0.009
1.52
1.06–2.16
FIG. 2. PSA progression-free probability curves demonstrating
difference in outcomes for patients with ECE (pT3a/b) with and
without PSM (p⫽0.0065).
FIG. 3. PSA progression-free probability curves demonstrating
difference in outcomes for patients with organ confined tumors (pT2)
with and without PSM (p⫽0.2761).
22.5% for patients with organ confined disease.4 Improved
preoperative methods of identifying the likely sites of ECE
and appropriate adjustment of surgical technique with wider
resection of surrounding tissues can decrease the likelihood
of a PSM. Indeed our PSM rate in patients with ECE at our
center during the last 3 years was 19% of 217 patients (PTS
and JAE).
Previous reports examining the impact of PSM on cancer
control outcomes after RP excluded patients who received AT
from analysis.14, 15 By doing so some patients with a PSM
who were at high risk for recurrence were excluded from
analysis, favorably distorting the recurrence rate of other
patients with PSM. In the current study we assessed the
significance of a PSM using multiple methods of analysis
FIG. 4. Trend in margin status and pathological stage during
study period. Using logistic regression analysis year of surgery
(p⫽0.02) and pathological stage (p⫽0.001) were significant suggesting change in surgical technique and favorable stage migration contributed to overall decrease in PSM.
accounting for the patients who received AT. To compare
with previous reports we assessed 5 different methods of
examining patients receiving AT: 1) exclusion from analysis,
2) inclusion in the analysis and ignoring that they received
AT, 3) inclusion and censoring from analysis at the time AT
was given, 4) treatment failure when AT was given and 5)
considering AT a time dependent covariate. The initial 4
methods each bias the outcome for the remaining patients
with PSMs. Clearly method 5, in which AT is considered a
time dependent covariate, is the most appropriate means of
assessing the overall prognostic significance of PSM. This
statistical method includes all patients in the analysis and
recognizes that the covariate (receiving AT) may change over
time and incorporates these new values into an actuarial
model. Followup was divided into time before AT and time
after AT, thus appropriately recognizing the time of AT. By
not excluding or censoring patients, this statistical method
has the least potential for introducing bias into the analysis.
Our study again confirms the adverse prognostic significance of a PSM, along with preoperative serum PSA, RP
Gleason score, presence of ECE, SVI and LNI as adverse
prognostic factors for biochemical recurrence after radical
prostatectomy. In multivariate analysis a PSM was found to
be significant in 4 of 5 methods of examining patients who
received AT. A PSM was not significant in multivariate analysis using method 2, in which patients who received AT were
included in the analysis and the effect of the AT was ignored.
When considered as a time dependent covariate in method 5,
adjuvant therapy was itself found to be a significant predictor of outcome (p⫽0.009), suggesting it is effective in delaying
biochemical recurrence (table 2). This hypothesis has been
given extra support by a recent article demonstrating the
beneficial effect of adjuvant radiotherapy following radical
prostatectomy.19
In our previous study3 a PSM was only significant in pa-
POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS
tients with ECE, not in those with organ confined cancer
(pT2⫹) or advanced disease (positive seminal vesicle and/or
lymph nodes). In the current series a PSM was significant in
patients with extracapsular extension. The adverse impact of
positive margins was less apparent in men with organ confined or advanced cancers.
The strengths of the current study are that all specimens
were examined by the same pathologist using the same
pathological techniques, thereby eliminating variation in interpretation. The definition and diagnosis of a positive margin were uniform throughout the study, a factor lacking in
most previous reports. Furthermore, the prognostic impact of
PSM was examined using AT as a time dependent covariate.
The data presented in this study support the growing body of
evidence of the adverse impact of PSM and support its addition to the TNM staging system.
As in most other studies we used biochemical recurrence as
the reference point by which we measured the importance of
PSM. This end point is the easiest to measure and requires
less followup than disease specific survival or overall survival. Pound et al demonstrated that once biochemical recurrence occurred the most significant predictors of the development of metastases and of overall survival were time to
biochemical progression, Gleason score and PSA doubling
time.20 To further validate the significance of PSM, other
objective end points such as the development of metastatic
disease and disease specific survival should be analyzed.
CONCLUSIONS
We demonstrated the significance of a PSM in the radical
prostatectomy specimen when controlled for other clinical
and pathological factors. Patients with positive surgical margins are at a significantly higher risk for disease progression
than those without a PSM even in the presence of extraprostatic disease. Careful preoperative planning should allow
surgeons to modify the technique for each individual patient’s cancer, reducing the likelihood of a PSM.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
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