Faculty Collaboration Database

Genomic Classifier Performance in Intermediate-Risk Prostate Cancer: Results From NRG Oncology/RTOG 0126 Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys 2023 Oct 01;117(2):370-377

Date

05/04/2023

Pubmed ID

37137444

Pubmed Central ID

PMC10949135

DOI

10.1016/j.ijrobp.2023.04.010

Scopus ID

2-s2.0-85163341124 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

PURPOSE: 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. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up.

METHODS AND MATERIALS: After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy 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 failure, 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.

RESULTS: Two-hundred 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% confidence interval [CI], 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 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 with 21% for higher GC patients (P-interaction = .04).

CONCLUSIONS: 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 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.

Author List

Spratt DE, Liu VYT, Michalski J, Davicioni E, Berlin A, Simko JP, Efstathiou JA, Tran PT, Sandler HM, Hall WA, Thompson DJS, Parliament MB, Dayes IS, Correa RJM, Robertson JM, Gore EM, Doncals DE, Vigneault E, Souhami L, Karrison TG, Feng FY

Authors

Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of Wisconsin
William Adrian Hall MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Androgen Antagonists
Disease Progression
Genomics
Humans
Male
Neoplasm Grading
Prostate-Specific Antigen
Prostatic Neoplasms
Retrospective Studies