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 risk was 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 (with cases defined 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.
Written by:
Cooperberg MR, Davicioni E, Crisan A, Jenkins RB, Ghadessi M, Karnes RJ. Are you the author?
Departments of Urology and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA; GenomeDx Biosciences, Vancouver, British Columbia, Canada; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Urology, Mayo Clinic, Rochester, MN, USA.
Reference: Eur Urol. 2014 Jul 2. pii: S0302-2838(14)00521-1.
doi: 10.1016/j.eururo.2014.05.039
PubMed Abstract
PMID: 24998118
