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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

mailto:[email protected]





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)

PREDICTING PROSTATE CANCER SPECIFIC MORTALITY AFTER PROSTATECTOMY870



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.

PREDICTING PROSTATE CANCER SPECIFIC MORTALITY AFTER PROSTATECTOMY 871



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)




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.




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




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.

REFERENCES

1. Bill-Axelson A, Holmberg L, Filen F et al: Radical

prostatectomy versus watchful waiting in local-

ized prostate cancer: the Scandinavian prostate

cancer group-4 randomized trial. J Natl Cancer

Inst 2008; 100: 1144.

2. Draisma G, Etzioni R, Tsodikov A et al: Lead time

and overdiagnosis in prostate-specific antigen

screening: importance of methods and context.

J Natl Cancer Inst 2009;101:

374.

3. Stephenson AJ, Scardino PT, Eastham JA et al:

Postoperative nomogram predicting the 10-year

probability of prostate cancer recurrence after

radical prostatectomy. J Clin Oncol 2005; 23:

7005.

4. Kattan MW, Wheeler TM and Scardino PT: Post-

operative nomogram for disease recurrence after

radical prostatectomy for prostate cancer. J Clin

Oncol 1999; 17: 1499.

5. Stephenson AJ, Kattan MW, Eastham JA et al:

Prostate cancer-specific mortality after radical

prostatectomy for patients treated in the pros-

tate-specific antigen era. J Clin Oncol 2009; 27:

4300.

6. Greene FL, Page DL, Fleming ID et al: AJCC

Cancer Staging Manual, 6th ed. American Joint

Committee on Cancer. New York: Springer-Verlag

2002.

7. Dong F, Reuther AM, Magi-Galluzzi C et al:

Pathologic stage migration has slowed in the late

PSA era. Urology 2007; 70: 839.

8. Albertsen PC, Hanley JA and Fine J: 20-Year

outcomes following conservative management of

clinically localized prostate cancer. JAMA 2005;

293: 2095.

9. Cuzick J, Fisher G, Kattan MW et al: Long-term

outcome among men with conservatively treated

localised prostate cancer. Br J Cancer 2006; 95:

1186.

10. Parker C, Muston D, Melia J et al: A model of the

natural history of screen-detected prostate can-

cer, and the effect of radical treatment on overall

survival. Br J Cancer 2006; 94: 1361.

11. Epstein JI, Allsbrook WC Jr, Amin MB et al: The2005 International Society of Urological Pathol-

ogy (ISUP) Consensus Conference on Gleason

Grading of Prostatic Carcinoma. Am J Surg Pathol

2005; 29: 1228.

12. Klotz L, Zhang L, Lam A et al: Clinical results of

long-term follow-up of a large, active surveillance

cohort with localized prostate cancer. J Clin On-

col 2010; 28: 126.

13. Thompson IM, Tangen CM, Paradelo J et al:

Adjuvant radiotherapy for pathological T3N0M0

prostate cancer significantly reduces risk of me-

tastases and improves survival: long-term fol-

lowup of a randomized clinical trial. J Urol 2009;181: 956.

14. Freedland SJ, Humphreys EB, Mangold LA et al:

Risk of prostate cancer-specific mortality follow-

ing biochemical recurrence after radical prosta-

tectomy. JAMA 2005; 294: 433.

15. D’Amico AV, Moul JW, Carroll PR et al: Surrogate

end point for prostate cancer-specific mortality

after radical prostatectomy or radiation therapy.

J Natl Cancer Inst 2003; 95: 1376.

16. Zhou P, Chen MH, McLeod D et al: Predictors of

prostate cancer-specific mortality after radical

prostatectomy or radiation therapy. J Clin Oncol

2005; 23: 6992.

17. Van der Kwast TH, Bolla M, Van Poppel H et al:

Identification of patients with prostate cancer who

benefit from immediate postoperative radiotherapy:

EORTC 22911. J Clin Oncol 2007; 25: 4178.

18. Stephenson AJ, Shariat SF, Zelefsky MJ et al:

Salvage radiotherapy for recurrent prostate cancer

after radical prostatectomy. JAMA 2004; 291: 1325.

19. Trock BJ, Han M, Freedland SJ et al: Prostate

cancer-specific survival following salvage radio-therapy vs observation in men with biochemical

recurrence after radical prostatectomy. JAMA

2008; 299: 2760.

20. Vickers AJ, Bianco FJ, Serio AM et al: The sur-

gical learning curve for prostate cancer control

after radical prostatectomy. J Natl Cancer Inst

2007; 99: 1171.

21. Albertsen PC, Hanley JA, Barrows GH et al:

Prostate cancer and the Will Rogers phenome-

non. J Natl Cancer Inst 2005; 97: 1248.

22. Porter CR, Kodama K, Gibbons RP et al: 25-year

prostate cancer control and survival outcomes: a40-year radical prostatectomy single institution

series. J Urol 2006; 176: 569.

23. Johansson JE, Andren O, Andersson SO et al:

Natural history of early, localized prostate cancer.

JAMA 2004; 291: 2713.

24. Sanda MG, Dunn RL, Michalski J et al: Quality of

life and satisfaction with outcome among pros-

tate-cancer survivors. N Engl J Med 2008; 358:

1250.

25. D’Amico AV, Chen MH, Roehl KA et al: Preop-

erative PSA velocity and the risk of death from

prostate cancer after radical prostatectomy.

N Engl J Med 2004; 351: 125.


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