Back

Prostate Cancer

Combined Value of Validated Clinical and Genomic Risk Stratification Tools for Predicting Prostate Cancer Mortality in a High-risk Prostatectomy Cohort

By: Matthew R. Cooperberg a lowast , Elai Davicioni b , Anamaria Crisan b , Robert B. Jenkins c , Mercedeh Ghadessi b and R. Jeffrey Karnes d

European Urology, Volume 67 Issue 2, February 2015, Pages 326-333

Published online: 01 February 2015

Keywords: Prostate neoplasms, Prostatectomy, Biomarkers, RNA, Risk stratification, CAPRA-S

Abstract Full Text Full Text PDF (1,2 MB) Patient Summary

Abstract

Background

Risk prediction models that incorporate biomarkers and clinicopathologic variables may be used to improve decision making after radical prostatectomy (RP). We compared two previously validated post-RP classifiers—the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) and the Decipher genomic classifier (GC)—to predict prostate cancer–specific mortality (CSM) in a contemporary cohort of RP patients.

Objective

To evaluate the combined prognostic ability of CAPRA-S and GC to predict CSM.

Design, setting, and participants

A cohort of 1010 patients at high risk of recurrence after RP were treated at the Mayo Clinic between 2000 and 2006.High riskwas defined by any of the following: preoperative prostate-specific antigen >20 ng/ml, pathologic Gleason score ≥8, or stage pT3b. A case-cohort random sample identified 225 patients (withcasesdefined as patients who experienced CSM), among whom CAPRA-S and GC could be determined for 185 patients.

Outcome measurements and statistical analysis

The scores were evaluated individually and in combination using concordance index (c-index), decision curve analysis, reclassification, cumulative incidence, and Cox regression for the prediction of CSM.

Results and limitations

Among 185 men, 28 experienced CSM. The c-indices for CAPRA-S and GC were 0.75 (95% confidence interval [CI], 0.55–0.84) and 0.78 (95% CI, 0.68–0.87), respectively. GC showed higher net benefit on decision curve analysis, but a score combining CAPRA-S and GC did not improve the area under the receiver-operating characteristic curve after optimism-adjusted bootstrapping. In 82 patients stratified to high risk based on CAPRA-S score ≥6, GC scores were likewise high risk for 33 patients, among whom 17 had CSM events. GC reclassified the remaining 49 men as low to intermediate risk; among these men, three CSM events were observed. In multivariable analysis, GC and CAPRA-S as continuous variables were independently prognostic of CSM, with hazard ratios (HRs) of 1.81 (p < 0.001 per 0.1-unit change in score) and 1.36 (p = 0.01 per 1-unit change in score). When categorized into risk groups, the multivariable HR for high CAPRA-S scores (≥6) was 2.36 (p = 0.04) and was 11.26 (p < 0.001) for high GC scores (≥0.6). For patients with both high GC and high CAPRA-S scores, the cumulative incidence of CSM was 45% at 10 yr. The study is limited by its retrospective design.

Conclusions

Both GC and CAPRA-S were significant independent predictors of CSM. GC was shown to reclassify many men stratified to high risk based on CAPRA-S ≥6 alone. Patients with both high GC and high CAPRA-S risk scores were at markedly elevated post-RP risk for lethal prostate cancer. If validated prospectively, these findings suggest that integration of a genomic-clinical classifier may enable better identification of those post-RP patients who should be considered for more aggressive secondary therapies and clinical trials.

Patient summary

The Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) and the Decipher genomic classifier (GC) were significant independent predictors of prostate cancer–specific mortality. These findings suggest that integration of a genomic-clinical classifier may enable better identification of those post–radical prostatectomy patients who should be considered for more aggressive secondary therapies and clinical trials.

Take Home Message

Two validated risk prediction models, the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) and a genomic classifier (GC), were evaluated separately and in combination for prediction of prostate cancer–specific mortality in high-risk postprostatectomy patients. Both were independent predictors, but an integrated risk model combining CAPRA-S and GC identified a very high-risk patient subset that may benefit most from aggressive therapy.

Keywords: Prostate neoplasms, Prostatectomy, Biomarkers, RNA, Risk stratification, CAPRA-S.

Footnotes

a Departments of Urology and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA

b GenomeDx Biosciences, Vancouver, British Columbia, Canada

c Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

d Department of Urology, Mayo Clinic, Rochester, MN, USA

lowast Corresponding author. Department of Urology, University of California, San Francisco, 1600 Divisadero St., Box 1695, San Francisco, CA 94143-1695, USA. Tel. +1 415 515 3229.

These authors made equal contributions.

Place a comment

Your comment *

max length: 5000