Abstract
276 Background: Decipher is a genomic classifier (GC) that estimates risk of prostate cancer (PCa) distant metastases (DM) post-radical prostatectomy (RP). Herein, we validate the GC within the context of a randomized phase 3 trial. Methods: RP specimens from patients on the NRG/RTOG 9601 phase 3 placebo-controlled randomized trial of salvage radiotherapy (sRT) +/- 2 years of bicalutamide (NCT00002874) were centrally reviewed and the highest-grade tumor underwent RNA extraction. Samples passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to assign the GC score (scale 0-1). Our NCTN-CCSC approved pre-specified statistical plan (NRG-GU-TS002 CSC0075) included the primary objective of validating the ability of the GC to independently prognosticate the cumulative incidence of DM, with secondary endpoints of prostate cancer-specific mortality (PCSM) and overall survival (OS). Results: Of patients with tissue available, 352 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 13 years. On multivariable analysis, the GC (continuous variable) was independently associated with DM (HR 1.19 [95%CI 1.06-1.35], p=0.003), PCSM (HR 1.37 [95%CI 1.18-1.61], p<0.001), and OS (HR 1.16 [95%CI 1.06-1.28], p=0.002) after adjusting for age, race, Gleason score, T-stage, margin status, entry PSA, and treatment arm. The estimated absolute impact of bicalutamide on 12-year OS was less in patients with lower vs higher GC scores (2.4% vs 8.9%), further demonstrated in men receiving early sRT at PSA <0.7 ng/mL (-2.0% vs 5.0%). Conclusions: This is the first validation of this GC in a prospective randomized trial cohort and demonstrates association of the GC with DM and PCSM independent of standard clinicopathologic variables. The GC may help personalize shared decision-making to weigh the absolute benefit from the addition of bicalutamide to sRT.