ca de prostata 1
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Predicting 15-Year Prostate Cancer Specific Mortality After
Radical Prostatectomy
Scott E. Eggener,* Peter T. Scardino, Patrick C. Walsh, Misop Han, Alan W. Partin,
Bruce J. Trock, Zhaoyong Feng, David P. Wood,† James A. Eastham,
Ofer Yossepowitch, Danny M. Rabah, Michael W. Kattan, Changhong Yu,
Eric A. Klein and Andrew J. Stephenson‡
From the Section of Urology, University of Chicago Medical Center (SEE), Chicago, Illinois, Urology Service, Department of Surgery, Sidney
Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center (PTS, JAE), New York, New York, James
Buchanan Brady Urological Institute, Johns Hopkins School of Medicine (PCW, MH, AWP, BJT, ZF), Baltimore, Maryland, Department of
Urology, University of Michigan (DPW), Ann Arbor, Michigan, Rabin Medical Center (OY), Petach Tikvah, Israel, Division of Urology,
Department of Surgery, Princess Johara Alibrahim Center for Cancer Research, King Saud University (DMR), Riyadh, Saudi Arabia,
and Glickman Urological and Kidney Institute (EAK, AJS) and Department of Quantitative Health Sciences (CY), Cleveland Clinic (MWK),
Cleveland, Ohio
Purpose: Long-term prostate cancer specific mortality after radical prostatec-tomy is poorly defined in the era of widespread screening. An understanding of
the treated natural history of screen detected cancers and the pathological riskfactors for prostate cancer specific mortality are needed for treatment decision
making.Materials and Methods: Using Fine and Gray competing risk regression analy-
sis we modeled clinical and pathological data, and followup information on 11,521patients treated with radical prostatectomy at a total of 4 academic centers from
1987 to 2005 to predict prostate cancer specific mortality. The model was vali-dated on 12,389 patients treated at a separate institution during the same period.
Median followup in the modeling and validation cohorts was 56 and 96 months,respectively.Results: The overall 15-year prostate cancer specific mortality rate was 7%.Primary and secondary Gleason grade 4 –5 (each p 0.001), seminal vesicle
invasion (p 0.001) and surgery year (p 0.002) were significant predictors of prostate cancer specific mortality. A nomogram predicting 15-year prostate cancer
specific mortality based on standard pathological parameters was accurate anddiscriminating with an externally validated concordance index of 0.92. When strat-
ified by patient age at diagnosis, the 15-year prostate cancer specific mortality ratefor pathological Gleason score 6 or less, 3 4, 4 3 and 8–10 was 0.2% to 1.2%, 4.2%
to 6.5%, 6.6% to 11% and 26% to 37%, respectively. The 15-year prostate cancerspecific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30%
for organ confined cancer, extraprostatic extension, seminal vesicle invasion andlymph node metastasis, respectively. Only 3 of 9,557 patients with organ confined,
pathological Gleason score 6 or less cancer died of prostate cancer.Conclusions: Poorly differentiated cancer and seminal vesicle invasion are the
prime determinants of prostate cancer specific mortality after radical prostatec-tomy. The prostate cancer specific mortality risk can be predicted with remark-
able accuracy after the pathological features of prostate cancer are known.
Key Words: prostate, prostatic neoplasms, prostatectomy,
mortality, nomograms
Abbreviations
and Acronyms
BCR biochemical recurrence
c-index concordance index
PCSM prostate cancer specific
mortality
PSA prostate specific antigen
PSADT PSA doubling time
Submitted for publication June 29, 2010.
Supported by a grant under the Robert
Wood Johnson Foundation Physician Faculty
Scholars Program and the Astellas-American
Urological Association Foundation Rising Stars
in Urology Program (AJS), National Institutes
of Health and National Cancer Institute SPORE
Grants P50CA92629 and P50CA58236, and
Maltz Family Foundation (EAK).
* Financial interest and/or other relationship
with Visualase.
† Financial interest and/or other relationship
with Intuitive Surgical, Urotoday and Amgen.
‡ Correspondence: Urologic Oncology, Glick-
man Urological and Kidney Institute, Cleveland
Clinic, 9500 Euclid Ave., Desk Q10, Cleveland,Ohio 44195-0001 (telephone: 216-445-1062; FAX:
216-445-9628; e-mail: [email protected]).
0022-5347/11/1853-0869/0 Vol. 185, 869-875, March 2011
THE JOURNAL OF UROLOGY® Printed in U.S.A.
© 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. DOI:10.1016/j.juro.2010.10.057www.jurology.com 869
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PROSTATE cancer typically has a protracted natural
history. In the absence of definitive local therapy the15-year PCSM is approximately 20%.1 This risk may
be substantially less in men living in regions wherePSA screening is prevalent since the estimated lead
time with screening is 5 to 11 years.2
Ideally treatment decision making should bebased in part on accurate estimates of PCSM. No-mograms predicting the risk of BCR after surgery
and radiation therapy are available.3,4 However,BCR is not a surrogate end point for PCSM since
increasing PSA may pose little threat to longevity inmany patients.
Nomograms that predict PCSM are needed. Us-ing pretreatment parameters, including PSA, biopsy
Gleason score and clinical stage, 15-year PCSM af-ter radical prostatectomy can be predicted for men
treated in the PSA era using a recently developed
nomogram.5
The accuracy of this nomogram wasonly slightly better than midway between randomchance and perfect discrimination, highlighting the
imperfect prognostic information contained in clini-cal grade and stage. To more rigorously guide treat-
ment decision making we constructed a nomogramfor PCSM based on prostate cancer pathological fea-
tures.
METHODS
A total of 11,521 consecutive patients with localized prostate
cancer were treated with radical prostatectomy at Memorial
Sloan-Kettering Cancer Center, Cleveland Clinic, Univer-sity of Michigan and Baylor College of Medicine between
1987 and 2005. They served as the modeling cohort for
nomogram development. For validation 12,389 patients sim-
ilarly treated at Johns Hopkins University during the same
period were used. Patients who received prior androgen de-
privation or radiation therapy were excluded from analysis.
Surgical specimens were evaluated by genitourinary
pathologists at each institution. Pathological stage was
assigned according to American Joint Committee on Can-
cer criteria.6 Tertiary Gleason scores were not assessed
since they were not available from all study sites. Second-
ary therapy was uncommonly administered in the absence
of BCR. A total of 788 men in the modeling cohort receivedpostoperative radiotherapy, of whom 756 (96%) had de-
tectable preradiotherapy PSA. Overall 1,045 men (9%) in
the modeling cohort received androgen deprivation ther-
apy after radical prostatectomy for BCR or clinical pro-
gression.
Death was attributed to prostate cancer if based on
medical record review there was evidence of a castrate
resistant disease state with metastases or prostate cancer
was listed as a cause of death on the death certificate. In
the modeling and validation cohorts median followup was
56 (IQR 24-93) and 96 months (IQR 60-144), respectively.
A total of 6,818 and 1,650 survivors had greater than 10
and 15 years of followup, respectively.For nomogram construction we used Fine and Gray
competing risk regression analysis to model clinical pa-
rameters and followup data. PSA before radical prostatec-
tomy and surgery year were modeled with restricted cubic
splines due to suspected nonlinear effects. Primary and
secondary pathological Gleason grades were modeled as
binary categorical variables (3 or less and 4 or greater). All
decisions with respect to variables entered into the models
(age, PSA, primary and secondary Gleason grade, extra-
capsular extension, seminal vesicle invasion, lymph node
metastasis, surgical margin status and surgery year) and
coding were made a priori.
For external validation of the model we assessed dis-
crimination and calibration when applied to the indepen-
dent validation cohort. Discrimination was quantified us-
ing the c-index, which is similar to the ROC AUC.
Calibration refers to the correlation between predicted
probability of PCSM and actual outcome. All statistical
analysis was done with S-Plus (TIBCO®) with additional
functions called Design added. All p values resulted from
using 2-sided statistical tests.
RESULTS
Table 1 lists clinical features of the modeling and validation cohorts. Overall 338 patients died of pros-
tate cancer and 1,204 died of another cause. In themodeling and validation cohorts mean 15-year PCSM
was 7% (range 6% to 9%) and 4% (range 3% to 5%),and 15-year all-cause mortality was 33% (range 30% to
36%) and 16% (range 14% to 17%), respectively. Over-all 108 PCSM events (32%) occurred in patients
treated after 1995, when the stage migration effect of
PSA screening appears to have stabilized.
5,7
Table 1. Clinical and pathological characteristics of patients
in modeling and validation cohorts
Modeling Validation
Median age (IQR) 60 (56–65) 58 (54–63)
No. surgery yr (%):
1987–1992 1,073 (9) 1,345 (11)
1993–1998 3,169 (28) 3,899 (31)
1999–2005 7,279 (63) 7,145 (58)
Median ng/ml PSA (IQR) 6.0 (4.4–8.8) 5.9 (4.2–8.6)
Pathological Gleason score (%):
2–6 4,305 (37) 7,771 (62)7 (34) 4,866 (42) 2,939 (24)
7 (43) 1,303 (11) 953 (8)
8–10 631 (6) 726 (6)
No. pathological stage (%):
Organ confined 8,051 (70) 7,997 (64)
Extraprostatic extension, no seminal
vesicle invasion or lymph node
metastasis evidence
2,322 (20) 3,589 (29)
Seminal vesicle invasion, no lymph
node metastasis evidence
668 (6) 480 (4)
Lymph node metastasis 359 (3) 318 (3)
No. pos surgical margins (%) 2,607 (23) 1,646 (13)
Median mos followup (IQR) 56 (24–93) 95 (60–139)
No. mortality (%):
PCSM 157 (1.4) 190 (1.6)Competing cause mortality 621 (5) 506 (4)
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On multivariate analysis primary and secondary
Gleason grade 4–5 (each p 0.001), seminal vesicleinvasion (p 0.001) and surgery year (p 0.002)
were the only parameters significantly associatedwith PCSM in the modeling cohort. A nomogram
based on 8 standard parameters was developed to
predict the 15-year PCSM risk (fig. 1). Surgery yearwas included in the model and predictions were ad-
justed for treatment year. The nomogram was accu-
rate and discriminating with an externally validatedc-index of 0.92 and predictions closely approximated
actual outcomes at 15 years (fig. 2). Nomogram pre-dictions were similarly robust when applied to pa-
tients treated in the early (1987 to 1994) and later(1995 to 2005) PSA era (c-index 0.89 and 0.93, re-
spectively).Given the important prognostic significance of
pathological grade and stage, the PCSM risk was
analyzed for these parameters, stratifying for pa-tient age at diagnosis and considering all 23,910 inthe study (table 2). In patients with pathological
Gleason 6 or less cancer the PCSM risk at 15 to 20years was negligible (1.2% or less) and substantially
less than the risk of death from competing causesregardless of age at diagnosis (fig. 3). In contrast, the PCSM risk in men with pathological Gleason 8–10
cancer was generally 31% or greater at 15 to 20
years in the subgroups analyzed. The risk of deathfrom prostate cancer at 15 to 20 years in these men
was substantially greater than the risk of deathfrom competing causes even at age 70 years or
greater. There were no substantial differences in15-year PCSM between Gleason 3 4 (4.2% to 6.5%)
and Gleason 4 3 (6.6% to 11%) since the 95% CIsoverlapped at all time points.
A similar pattern was seen when long-term PCSMwas analyzed according to pathological stage (fig. 4). A
negligible PCSM risk at 15 to 20 years was observed inmen with organ confined cancer (0.8% to 1.5%) and a
substantially increased risk was observed in thosewith seminal vesicle invasion or lymph node metasta-
sis (22% to 42%), particularly in those 69 years old oryounger at diagnosis. Isolated extraprostatic extension
did not portend a particularly poor prognosis since the
PCSM risk in men 69 years old or younger at diagnosiswas 2.9% to 7% at 15 to 20 years, which was generallysubstantially less than the risk of death from compet-
ing causes (6.6% to 24%). Patients with organ con-fined, pathological Gleason 6 or less cancer had a par-
ticularly favorable prognosis since only 3 deaths fromprostate cancer were observed in a total of 9,557 men.
DISCUSSION
Radical prostatectomy is widely used for localized
prostate cancer. In men with screen detected pros-tate cancer the PCSM risk has been difficult to pre-
dict due to the stage migration caused by screening.
Points
PSA
AGE
Extracapsular Extension
Positive Surgical Margin
Seminal Vesicle Invasion
Lymph Node Metastases
Primary Gleason Score
Secondary Gleason Score
Total Points
Predicted 15-year PCSM
0
0
100
80
NO
POS
NEG
YES
NO
NO
1-3
1-3
4-5
4-5
YES
YES
60 40
15
10 20 30 40 50 60 70 80 90 100
0 50 100
0. 01 0. 05 0.1 0. 2 0.4 0. 6 0.8 0.9 0. 99
150 200 250 300 350 400 450
Figure 1. Nomogram predicting 15-year PCSM after radical
prostatectomy based on preoperative PSA and prostate cancer
pathological features. Instructions: locate patient primary Glea-
son grade on respective axis. Draw straight line up to points axis
to determine how many points toward PCSM he receives for
primary Gleason grade. Repeat this process for other 3 param-
eters. Sum points and locate this value on total points axis.
Draw straight line down to find patient probability of death fromprostate cancer within 15 years of treatment.
Predicted 15-year PCSM
O b s e r v e d 1 5 - y e a r P
C S M
0.8
0.6
0.4
0.2
0.00.0 0.2 0.4 0.6 0.8
Figure 2. Nomogram calibration. Line at 45-degree angle indi-
cates ideal nomogram reference line.
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To our knowledge this study is the largest in the
PSA era to evaluate death from prostate cancer afterradical prostatectomy. Gleason score 8–10 and sem-
inal vesicle invasion were the prime determinants of PCSM and a nomogram based on these and other
parameters predicts 15-year PCSM with exceptionalaccuracy. This nomogram should be useful for pa-
tient counseling and the need for secondary therapy.It provides important information about the treated
natural history of prostate cancer and identifies can-cers that pose the greatest and least threat to sur-
vival.The results of our study help sharpen the focus of
therapy in men with screen detected, localized pros-tate cancer. Patients with Gleason score 8–10, sem-
inal vesicle invasion or lymph node metastasis areat substantially increased risk for PCSM than those
without these features. However, 15-year PCSM inthese men at high risk was lower than expected
(range 22% to 39%). This finding is significant sincemen with these pathological features were previ-
ously thought to be incurable and considered bysome to be unsuitable candidates for radical prosta-
tectomy. While curing cancer is the ultimate goal of
therapy, treatment is not necessarily futile when
cure is not possible. Clearly many patients withincurable cancer are not destined to die of prostate
cancer after radical prostatectomy with or withoutsecondary therapy. While it is not known how these
patients at high risk would have fared without localtherapy, studies in other patients at high risk with
clinically localized disease who were treated withoutcurative intent suggest substantially a higher risk of
PCSM.
8–10
Most contemporary men treated with radical
prostatectomy have organ confined and/or patho-logical Gleason 6 cancer with a negligible risk of
death after radical prostatectomy. With the recentrevision of the Gleason grading system nonorgan
confined, pathological Gleason 6 or less cancer isnow a profoundly uncommon occurrence.11 Thus,
we may have observed even fewer cancer specificdeaths in men with pathological Gleason 6 or less
cancer had surgical specimens been subjected to acontemporary pathological review. Radical prosta-
tectomy is highly effective for well differentiatedcancers but may be unnecessary in a significant
proportion of these men since similar cancer spe-
Table 2. Probability of death from prostate cancer and competing causes after radical prostatectomy in 23,910 men in combined
modeling and validation cohorts by pathological Gleason score, pathological stage and age at diagnosis
Mean % 10-Yr (95% CI) Mean % 15-Yr (95% CI) Mean % 20-Yr (95% CI)
PCSM
Competing Cause
Mortality PCSM
Competing Cause
Mortality PCSM
Competing Cause
Mortality
Age less than 60 Gleason score:
6 or less 0.1 (0.03–0.3) 2.4 (2–3) 0.6 (0.2–1.5) 6.0 (4.5–8) 1.2 (0.4–3) 11 (7–17)
3 4 2.2 (1.5–3.3) 3.2 (2.4–4.4) 4.7 (3–6.8) 6.5 (4.6–8.8) 16 (7.2–29) 14 (8–23)
4 3 5.6 (3.4–8.7) 4.9 (3–7.6) 9 (5.5–14) 10 (5.4–16) 9 (5.5–14) 10 (5.4–16)
8–10 15 (11–20) 3.3 (1.7–5.9) 31 (23–39) 6.5 (3.5–11) 31 (23–39) 16 (6.5–28)
Organ confined 0.5 (0.3–8.4) 2.6 (2.1–3.2 0.8 (0.3–1.6) 6.8 (5–9) 0.8 (0.3–1.6) 12 (6.3–19)
Extraprostatic extension 1.7 (0.1–2.5) 3.6 (2.7–4.6) 2.9 (2–4.2) 6.6 (5–8.5) 7 (2–16) 12 (8.2–16)
Seminal vesicle invasion 8.4 (5.2–12) 2.3 (0.9–4.8) 27 (18–37) 5.3 (2.3–10) 33 (19–47) 5.3 (2.3–10)
Lymph node metastasis 18 (13–24) 2.8 (1.2–5.9) 30 (22–38) 6.5 (3.1–12) 41 (27–55) 16 (5.6–31)
Age 60–69
Gleason score:
6 or Less 0.1 (0.03–0.2) 6 (4.6–6.4) 0.2 (0.01–0.6) 12 (10–14) 0.2 (0.01–0.6) 33 (23–42)
3 4 1.7 (1.1–2.5) 6.3 (5.2–7.6) 4.2 (2.8–5.9) 14 (12–17) 9.0 (4.8–15) 32 (19–45)
4 3 4.4 (2.6–7.1) 4.7 (3–6.9) 11 (6.9–16) 11 (6.9–16) 23 (13–34) 34 (9–62)
8–10 13 (9.7–17) 7.2 (4.8–10) 26 (20–32) 16 (11–21) 39 (25–53) 26 (17–36)Organ confined 0.5 (0.3–8.7) 5 (4.2–5.8) 1 (0.5–1.8) 12 (9.7–14) 1.4 (0.7–2.7) 29 (19–40)
Extraprostatic extension 1.9 (1.3–2.7) 6.6 (5.5–7.9) 3.9 (2.8–5.3) 14 (12–16) 6.6 (4.1–9.9) 34 (24–43)
Seminal vesicle invasion 8.8 (5.8–12) 8.5 (5.6–12) 22 (15–29) 16 (11–23) 26 (18–36) 47 (17–72)
Lymph node metastasis 12 (7.7–17) 7.2 (4–12) 22 (15–30) 13 (8–20) 42 (26–57) 16 (9–26)
Age 70–79
Gleason score:
6 or less 0 11 (6.7–17) 1.2 (0.1–5.8) 22 (13–32) 1.2 (0.1–5.8) 30 (17–44)
3 4 1.3 (0.4–3.6) 16 (11–22) 6.5 (1.9–15) 33 (22–44) 17 (2–44) 61 (29–82)
4 3 6.6 (2–15) 18 (9.7–29) 6.6 (2–15) 23 (11–37) 18 (3–45) 23 (11–37)
8–10 18 (9–31) 11 (4–22) 37 (17–57) 11 (4–22) 37 (17–57) 21 (5–46)
Organ confined 1.4 (0.4–4) 14 (9.2–19) 1.5 (0.4–4) 18 (12–25) 1.5 (0.4–4) 43 (17–68)
Extraprostatic extension 0.5 (0.1–2.6) 12 (7.3–18) 10 (4–19) 27 (18–38) 20 (7–39) 41 (26–56)
Seminal vesicle invasion 13 (6–23) 22 (13–34) 15 (7–26) 36 (18–55) 15 (7–26) 36 (18–55)
Lymph node metastasis 23 (8–43) 10 (1.5–27) 23 (8–43) 10 (1.5–27) 23 (8–43) 10 (1.5–27)
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cific survival may have been achieved without im-mediate therapy. These results provocatively call
into question the need for any immediate treat-ment in men with pathological well differentiated
cancer, provided that they can be accurately de-termined at diagnosis. Ten-year prostate cancer
specific survival was 97.2% in a low risk cohort of men on active surveillance in a recent study.12
However, few healthy young men with low riskcancer are treated with this approach due to con-
cern that clinical grading and staging may ini-tially underestimate the threat. It is possible that
active surveillance would become more widely ac-cepted if these concerns could be successfully over-
come by more complete biopsy sampling, advancedimaging techniques or novel biomarkers.
In contrast, these data suggest that the greatestrelative benefit of surgery compared to surveil-
lance is in men with aggressive cancer, even thoseunlikely to be cured by surgery alone based on a
BCR end point. In these men combining surgerywith the judicious use of adjuvant or salvage ra-
diation therapy is likely to have the greatest im-pact on decreasing PCSM. For example, adjuvant
radiation therapy improves survival in men with
pathologically advanced prostate cancer and pa-tients with seminal vesicle invasion appear to de-
rive the greatest relative benefit.13 While to ourknowledge the superiority of adjuvant vs salvage
radiation therapy has yet to be proved in a ran-domized trial, adjuvant radiation therapy would
appear to be a reasonable approach in men withseminal vesicle invasion, given the high relative
risk of BCR and PCSM.Numerous investigators have reported that the
PCSM risk in patients with BCR can be predictedusing PSADT.14–16 However, PSADT is useful only
in patients in whom BCR has manifested and awaiting period of 6 to 24 months is required for an
accurate calculation. These factors limit the clinicalusefulness of PSADT since the critical period for
treatment decisions is the immediate postoperativeperiod or when PSA first begins to increase. Postop-
erative radiation therapy is most effective whengiven in the adjuvant setting, or as salvage therapy
when serum PSA first attains detectable levels. Assuch, the current nomogram is anticipated to be
useful to select men for secondary radiation therapywho are at substantial risk for death from prostate
cancer.
Figure 3. PCSM (black areas) and mortality from competing causes (gray areas) by pathological Gleason score and patient age at
diagnosis.
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An extraordinary finding of our study was the
high accuracy of the nomogram using standard
pathological parameters, which is unprecedented forpredictive models in oncology. The c-index of 0.92
indicates that its performance approaches that of aperfectly discriminating model. The c-index of a sim-
ilar model based on pretreatment clinical stage andbiopsy Gleason score was 0.82, highlighting the in-
accuracy of clinical vs pathological stage and grade.5
Decisions regarding treatment for localized prostate
cancer rely on clinical stage and grade. Our studyhighlights that novel strategies should focus on pre-
dicting the pathological grade and stage of prostatecancer before treatment. This should lead to im-
proved patient selection for active surveillance forlow risk cancer and multimodal therapy for aggres-
sive cancer.By squarely placing the risk of PCSM on the
presence of Gleason score 8–10 cancer and seminal vesicle invasion the relative importance of other
prognostic factors is placed in appropriate context.The relative lack of importance of many factors im-
plicated in BCR for PCSM highlights the limitationof using the former as an end point. Factors other
than aggressive tumor biology may increase the
BCR risk. For example, positive surgical margins
appear to increase the risk of local recurrence17 but
they were not significantly associated with PCSM.The low risk of PCSM in men with isolated ex-
traprostatic extension and positive surgical marginscalls into question the need for adjuvant radiation
therapy despite evidence from a randomized trial of improved overall and metastasis-free survival com-
pared to a largely observational strategy.13 Salvageradiation therapy at the earliest sign of BCR ap-
pears to be a reasonable alternative.
18,19
Year of surgery was significantly associated with
PCSM with an improved prognosis in contemporarypatients. Possible explanations for this finding in-
clude stage migration induced by widespread PSAscreening, recognition and application of effective
secondary therapy or technical improvements inradical prostatectomy.20 Significant interaction was
observed between tumor grade and treatment yearwith higher Gleason scores assigned to contempo-
rary patients (data not shown), consistent with re-cent modifications to the Gleason grading system.21
The predictions of our model are anticipated to be valid when applied to patients treated after 2005
since we previously reported that the favorable prog-
Figure 4. PCSM (black areas) and mortality from competing causes (gray areas) by pathological stage and patient age at diagnosis
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nosis associated with more recent surgery year has
stabilized since 1998.5
The nomogram predicts the probability of PCSM
within 15 years but patients appear to be at risk forPCSM up to 20 years after treatment.22 A recent
study of patients treated without curative intent in
the pre-PSA era suggested an acceleration in PCSMafter 15 years,23 although a contradictory findingwas reported in a separate study.8 The long-term
risk of PCSM was low in patients in our study butwe do not know how they would have fared without
radical therapy. Likewise we are unable to comparethe effectiveness of radical prostatectomy to that of
external beam radiation therapy or brachytherapy.Our model considers only PCSM and does not con-
sider health related quality of life issues, which thepatient must also consider when formulating a
treatment decision.24 We also did not consider all
potential important prognostic parameters, such as
PSA velocity,25 although it did not improve the ac-
curacy of our preoperative nomogram.5 Lastly, ourstudy consists of men treated at high volume, ter-
tiary referral centers and, thus, the nomogram maynot be as accurate in men treated in other settings.
CONCLUSIONS
Pathological Gleason 8–10 cancer and seminal vesicle
invasion are the prime determinants of PCSM afterradical prostatectomy. The PCSM risk in men with
organ confined, well differentiated cancer is negligible.PCSM can be accurately predicted by a nomogram
based on the clinical and pathological features of pros-tate cancer. By focusing on PCSM this study repre-
sents a critical reappraisal of key prostate cancer prog-nostic factors and offers meaningful insight into the
treated natural history of screen detected prostate
cancer after radical prostatectomy.
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