Faculty Collaboration Database

Transcriptomic Analysis of Localized High-risk Prostate Cancer Improves Prognostication and Identifies Benefit from Adding Docetaxel to Definitive Radiotherapy with Androgen Suppression in the NRG Oncology/RTOG 0521 Phase 3 Trial. Eur Urol Oncol 2025 Aug;8(4):968-976

Date

07/18/2025

Pubmed ID

40675873

Pubmed Central ID

PMC12370384

DOI

10.1016/j.euo.2025.04.009

Scopus ID

2-s2.0-105016534623 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

BACKGROUND AND OBJECTIVE: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.

METHODS: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from NRG/RTOG 0521. The primary objective was to validate the independent prognostic ability of GC for metastasis-free survival (MFS). Treatment effects in luminal proliferating (LP) and non-LP cell subtypes were examined in relation to MFS, OS, and distant metastasis (DM).

KEY FINDINGS AND LIMITATIONS: Samples were obtained from 283 patients and yielded 183 GC scores. Over median follow-up of 9.9 yr, 67 metastasis events were observed, including 34 DM events. Multivariable analysis revealed that GC was independently associated with DM (subdistribution hazard ratio 1.45) and MFS (hazard ratio 1.20). No biomarker-by-treatment interaction with GC and docetaxel was detected. The 10-yr restricted mean survival time difference in OS with CT was 13.7 mo for LP (p = 0.053) and 2.5 mo for non-LP (p = 0.63) tumors.

CONCLUSIONS AND CLINICAL IMPLICATIONS: The Decipher GC score was independently associated with DM and MFS, and LP tumors may benefit from addition of CT. Validation of these findings may allow more effective use of CT in men with localized PC. The original NRG/RTOG 0521 trial is registered on ClinicalTrials.gov as NCT00288080.

Author List

Phillips RM, Proudfoot JA, Davicioni E, Liu Y, Spratt DE, Simko JM, Den RB, Pollack A, Rosenthal SA, Sartor AO, Sweeney CJ, Attard G, Longoria L, Patel S, Straza MW, Efstathiou JA, Shah AB, Hoffman KE, Rodgers JP, Sandler HM, Feng FY, Tran PT

Author

Michael W. Straza MD, PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

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

Aged
Androgen Antagonists
Chemoradiotherapy
Gene Expression Profiling
Humans
Male
Middle Aged
Prognosis
Prostatic Neoplasms
Taxoids
Transcriptome