Validation of a 22-Gene Genomic Classifier in Patients with Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial

Abstract

Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer. Objective: To validate the GC in the context of a randomized phase 3 trial. Design, Setting, and Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019. Intervention: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. Main Outcomes and Measures: The preplanned primary end point of this study was the independent association of the GC with the development of DM. Results: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P =.006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P