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Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic
R Jeffrey Karnes1, Voleak Choeurng2, Ashley E Ross3
1Department of Urology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Background:
Risk of prostate cancer-specific mortality (PCSM) is highly variable for men with adverse pathologic features at radical prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions.
Objective:
Validate the 22 gene Decipher genomic classifier (GC) to predict PCSM in men with adverse pathologic features after RP.
Design, Setting, And Participants:
Men with adverse pathologic features: pT3, pN1, positive margins, or Gleason score >7 who underwent RP in 1987-2010 at Johns Hopkins, Cleveland Clinic, Mayo Clinic, and Durham Veteran's Affairs Hospital. We also analyzed subgroups at high risk (prostate-specific antigen >20 ng/ml, RP Gleason score 8-10, or stage >pT3b), or very high risk of PCSM (biochemical recurrence in<2 yr [BCR2], or men who developed metastasis after RP [MET]).
Outcome Measurements And Statistical Analysis:
Logistic regression evaluated the association of GC with PCSM within 10 yr of RP (PCSM10), adjusted for the Cancer of the Prostate Risk Assessment Postsurgical Score (CAPRA-S). GC performance was evaluated with area under the receiver operating characteristic curve (AUC) and decision curves.
Results And Limitations:
Five hundred and sixty-one men (112 with PCSM10), median follow-up 13.0 yr (patients without PCSM10). For high GC score (> 0.6) versus low-intermediate (≤ 0.6), the odds ratio for PCSM10 adjusted for CAPRA-S was 3.91 (95% confidence interval: 2.43-6.29), with AUC=0.77, an increase of 0.04 compared with CAPRA-S. Subgroup odds ratios were 3.96, 3.06, and 1.95 for high risk, BCR2, or MET, respectively (all p<0.05), with AUCs 0.64-0.72. GC stratified cumulative PCSM10 incidence from 2.8% to 30%. Combined use of case-control and cohort data is a potential limitation.
Conclusions:
In a large cohort with the longest follow-up to date, Decipher GC demonstrated clinically important prediction of PCSM at 10 yr, independent of CAPRA-S, in men with adverse pathologic features, BCR2, or MET after RP.
Patient Summary:
Decipher genomic classifier may improve treatment decision-making for men with adverse or high risk pathology after radical prostatectomy.