R Jeffrey Karnes1, Voleak Choeurng2, Ashley E Ross3, Edward M Schaeffer4, Eric A Klein5, Stephen J Freedland6, Nicholas Erho2, Kasra Yousefi2, Mandeep Takhar2, Elai Davicioni2, Matthew R Cooperberg7, Bruce J Trock8. 1. Department of Urology, Mayo Clinic College of Medicine, Rochester, MN, USA. 2. GenomeDx Biosciences, Vancouver, BC, Canada. 3. James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. 4. James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Urology, Northwestern University School of Medicine, Chicago, IL, USA. 5. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 6. Surgery Section, Durham Veteran Affairs Medical Center, Durham, NC, USA; Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Department of Urology and Epidemiology and Biostatistics, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA. 8. James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: btrock@jhmi.edu.
Abstract
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.
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.
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