Analysis of a biopsy-based genomic classifier in high-risk prostate cancer: Meta-analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 phase III randomized trials.

Decipher is a genomic classifier (GC) prospectively validated post-prostatectomy. Herein, we validate the performance of the GC in pre-treatment biopsy samples within the context of three randomized phase III high-risk definitive radiotherapy trials.

A pre-specified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled on the NRG/RTOG 9202, 9413, and 9902 phase III randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability for the GC for distant metastases (DM), and secondary for prostate cancer-specific mortality (PCSM) and overall survival (OS) with Cox univariable (UVA) and multivariable analyses (MVA).

GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9, 13). In the pooled cohort, on UVA, the GC was shown to be a prognostic factor for DM (per 0.1 unit; sHR 1.29, 95%CI 1.18-1.41, p<0.001), PCSM (sHR 1.28, 95%CI 1.16-1.41, p<0.001), and OS (HR 1.16, 95%CI 1.08-1.22, p<0.001). On MVA, the GC (per 0.1 unit) was independently associated with DM (sHR 1.22, 95%CI 1.09-1.36), PCSM (sHR 1.23, 95%CI 1.09-1.39), and OS (HR 1.12, 95%CI 1.05-1.20) after adjusting for age, PSA, Gleason score, cT-stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy (ADT) but the absolute improvement in outcome varied by GC risk.

This is the first validation of a gene expression biomarker on pre-treatment prostate cancer biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state and GC can improve risk stratification to help personalize shared decision-making.

International journal of radiation oncology, biology, physics. 2022 Dec 31 [Epub ahead of print]

Paul L Nguyen, Huei-Chung Rebecca Huang, Daniel E Spratt, Elai Davicioni, Howard M Sandler, William U Shipley, Jason A Efstathiou, Jeffry P Simko, Alan Pollack, Adam P Dicker, Mack Roach, Seth A Rosenthal, Kenneth L Zeitzer, Lucas C Mendez, Alan C Hartford, William A Hall, Anand B Desai, Rachel A Rabinovitch, Christopher A Peters, Joseph P Rodgers, Phuoc Tran, Felix Y Feng

Brigham and Women's Hospital, Boston, MA. Electronic address: ., GenomeDx Inc., Vancouver, BC, Canada/Decipher Biosciences, San Diego, CA., UH Cleveland Medical Center, Cleveland OH., Decipher Biosciences, San Diego, CA., Cedars-Sinai Medical Center, Los Angeles, CA., Massachusetts General Hospital, Harvard Medical School, Boston, MA., UCSF Medical Center-Mount Zion, San Francisco, CA., University of Miami Miller School of Medicine, Miami, FL., Thomas Jefferson University Hospital, Philadelphia, PA., Sutter Cancer Centers Radiation Oncology Services, Roseville, CA., Einstein Medical Center Philadelphia, PA accruals Thomas Jefferson University Hospital., London Regional Cancer Program, London, ON., Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH., Froedtert and the Medical College of Wisconsin, Milwaukee, WI., Summa Health System, Akron, OH., University of Colorado Denver, Aurora, CO., Northeast Radiation Oncology Center, Dunmore, PA., NRG Oncology Statistics and Data Management Center., University of Maryland, Baltimore, MD., UCSF Medical Center-Mission Bay, San Francisco, CA.