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

Authors

Ryan M. Phillips
James A. Proudfoot
Elai Davicioni
Yang Liu
Daniel E. Spratt
Jeff M. Simko
Robert Den, Thomas Jefferson UniversityFollow
Alan Pollack
Seth A. Rosenthal
A. Oliver Sartor
Christopher J. Sweeney
Gerhardt Attard
Leslie Longoria
Samir Patel
Michael W. Straza
Jason A. Efstathiou
Amit B. Shah
Karen E. Hoffman
Joseph P. Rodgers
Howard M. Sandler
Felix Y. Feng
Phuoc T. Tran

Document Type

Article

Publication Date

7-17-2025

Comments

This article is the author's final published version in European Urology Oncology, Volume 8, Issue 4, 2025, Pages 968-976.

The published version is available at https://doi.org/10.1016/j.euo.2025.04.009. Copyright © The Author(s).

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.

Recommended Citation

Phillips, Ryan M.; Proudfoot, James A.; Davicioni, Elai; Liu, Yang; Spratt, Daniel E.; Simko, Jeff M.; Den, Robert; Pollack, Alan; Rosenthal, Seth A.; Sartor, A. Oliver; Sweeney, Christopher J.; Attard, Gerhardt; Longoria, Leslie; Patel, Samir; Straza, Michael W.; Efstathiou, Jason A.; Shah, Amit B.; Hoffman, Karen E.; Rodgers, Joseph P.; Sandler, Howard M.; Feng, Felix Y.; and Tran, Phuoc T., "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" (2025). Jefferson Hospital Staff Papers and Presentations. Paper 66.
https://jdc.jefferson.edu/tjuhpapers/66

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English