Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era

Abstract

Purpose: The long-term risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy is poorly defined for patients treated in the era of widespread prostate-specific antigen (PSA) screening. Models that predict the risk of PCSM are needed for patient counseling and clinical trial design.

Methods: A multi-institutional cohort of 12,677 patients treated with radical prostatectomy between 1987 and 2005 was analyzed for the risk of PCSM. Patient clinical information and treatment outcome was modeled using Fine and Gray competing risk regression analysis to predict PCSM.

Results: Fifteen-year PCSM and all-cause mortality were 12% and 38%, respectively. The estimated PCSM ranged from 5% to 38% for patients in the lowest and highest quartiles of predicted risk of PSA-defined recurrence, based on a popular nomogram. Biopsy Gleason grade, PSA, and year of surgery were associated with PCSM. A nomogram predicting the 15-year risk of PCSM was developed, and the externally validated concordance index was 0.82. Neither preoperative PSA velocity nor body mass index improved the model's accuracy. Only 4% of contemporary patients had a predicted 15-year PCSM of greater than 5%.

Conclusion: Few patients will die from prostate cancer within 15 years of radical prostatectomy, despite the presence of adverse clinical features. This favorable prognosis may be related to the effectiveness of radical prostatectomy (with or without secondary therapy) or the low lethality of screen-detected cancers. Given the limited ability to identify contemporary patients at substantially elevated risk of PCSM on the basis of clinical features alone, the need for novel markers specifically associated with the biology of lethal prostate cancer is evident.

Fig 1.

(A) Prostate cancer–specific mortality (gold) and death from competing causes (blue) after radical prostatectomy. (B) Prostate cancer–specific mortality after radical prostatectomy stratified by validated preoperative nomogram predictions of 5-year prostate-specific antigen (PSA) progression-free probability (PFP) of 76% to 99% (blue), 51% to 75% (gray), 26% to 50% (gold), and 1% to 25% (red).

Fig 2.

(A) Preoperative nomogram predicting 10- and 15-year prostate cancer–specific mortality after radical prostatectomy. (B) Calibration of the nomogram. Dashed line indicates reference line where an ideal nomogram would lie. Instructions: Locate the patient's primary Gleason grade on the respective axis. Draw a straight line up to the Points axis to determine how many points toward prostate cancer–specific mortality he receives for his primary Gleason grade. Repeat this process for the other three parameters. Sum the points and locate this number on the Total Points axis. Draw a straight line down to find the patient's probability of dying as a result of prostate cancer within 10 or 15 years of treatment.

Fig 3.

Log relative hazard of prostate cancer–specific mortality (PCSM) associated with year of surgery after controlling for biopsy Gleason grade, pretreatment prostate-specific antigen (PSA), and clinical stage (dotted line) Performance of optimal model; (blue line) performance of nomogram.