Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk stratification in these patients. Herein, we assess the performance of the GC in men with intermediate-risk disease enrolled on xxxx with updated follow-up.
After National Cancer Institute approval, biopsy slides were collected from xxxx, a randomized phase III trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy vs 79.2 Gy of radiotherapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical-, local-failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors.
Two-hundred and fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio [sHR] 1.12, 95%CI 1.00-1.26, p=0.04), biochemical failure (sHR 1.22, 95%CI 1.10-1.37, p<0.001), distant metastasis (sHR 1.28, 95%CI 1.06-1.55, p=0.01), and PCSM (sHR 1.45, 95%CI 1.20-1.76, p<0.001). 10-year distant metastasis in GC low patients was 4% compared to 16% for GC high risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared to 21% for higher GC patients (p-interaction 0.04).
This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase III trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.
International journal of radiation oncology, biology, physics. 2023 May 01 [Epub ahead of print]
Daniel E Spratt, Vinnie Y T Liu, Jeff Michalski, Elai Davicioni, Alejandro Berlin, Jeff M Simko, Jason A Efstathiou, Phuoc T Tran, Howard M Sandler, William A Hall, Darby Js Thompson, Matthew B Parliament, Ian S Dayes, Rohann Jonathan Mark Correa, John M Robertson, Elizabeth M Gore, Desiree E Doncals, Eric Vigneault, Luis Souhami, Theodore G Karrison, Felix Y Feng
University Hospitals Seidman Cancer Center, Cleveland, OH. Electronic address: ., Veracyte, Inc., South San Francisco, CA., Washington University, St. Louis, MO., Princess Margaret Cancer Centre, Toronto, Canada., University of California, San Francisco, CA., Massachusetts General Hospital, Boston, MA., University of Maryland, Baltimore, MD., Cedars-Sinai Medical Center, Los Angeles, CA., Medical College of Wisconsin, Milwaukee, WI., Cross Cancer Institute, Edmonton, Canada., Hamilton Regional Cancer Centre, Ontario, Canada., London Regional Cancer Program, Ontario, Canada., Beaumont Health CCOP, Royal Oak, MI., Milwaukee VA Medical Center, Milwaukee, WI., Akron City Hospital, Akron, OH., CHU de Quebec Universite Laval, Quebec, Canada., McGill University, Quebec, Canada., NRG Oncology Statistics and Data Management Center, Philadelphia, PA.