Predicting dose response to prostate cancer radiotherapy: validation of a radiation signature in the randomized phase III NRG/RTOG 0126 and SAKK 09/10 trials.

Authors

Alan Dal Pra
Pirus Ghadjar
Hyunnam Ryu
James Proudfoot
Stefanie Hayoz
Jeff Michalski
Daniel Spratt
Yang Seagle Liu
Catherine Schär-Hostettler
John M. Robertson, Corewell Health East

Document Type

Article

Publication Date

5-2025

Publication Title

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

Abstract

BACKGROUND: The SAKK 09/10 trial randomized biochemically recurrent prostate cancer patients to salvage radiation 64 Gy versus 70 Gy, and the NRG/RTOG 0126 randomized intermediate-risk prostate cancer patients to definitive radiation 70.2 Gy versus 79.2 Gy. We investigated a previously developed Post-Operative Radiation Therapy Outcomes Score (PORTOS) to identify preferential benefit from radiation dose escalation (DE).

MATERIALS AND METHODS: PORTOS was evaluated in patients enrolled in SAKK 09/10 and NRG/RTOG 0126 with available tissue that passed quality control (n = 226, 215). PORTOS was evaluated in the published post-operative groups in SAKK 09/10 and in tertiles in NRG/RTOG 0126 as cut-offs had not been established for biopsy samples and definitive radiation patients. Clinical and molecular correlates in a real-world dataset of 42 407 prostatectomy and 31 107 biopsy samples were also analyzed.

RESULTS: In SAKK 09/10, the biomarker-treatment interaction was statistically significant between PORTOS (lower versus higher) and treatment arm for clinical progression-free survival. Only patients in the higher PORTOS group benefited from DE. In NRG/RTOG 0126, in patients with a lower tertile PORTOS, there was no difference in Phoenix biochemical failure (BF). However, for patients in the average and higher tertile PORTOS range, there was a significant benefit for DE for Phoenix BF. An interaction test indicated a significant difference in benefit for DE between higher and lower PORTOS groups. PORTOS was not strongly associated with clinicopathological variables in either trial or the large real-world dataset. In the latter, PORTOS was modestly associated with hypoxia signatures and strongly associated with immune signatures and subtypes.

CONCLUSION: In the SAKK 09/10 and RTOG 0126 randomized controlled trials, we demonstrated that PORTOS can potentially identify a subset of patients who benefit from DE, a subgroup that cannot be identified using clinicopathological or prognostic variables. These results suggest that PORTOS could be used clinically as a predictor of radiation response.

Volume

36

Issue

5

First Page

572

Last Page

582

Recommended Citation

Dal Pra A, Ghadjar P, Ryu HM, Proudfoot JA, Hayoz S, Michalski JM, et al [Robertson JM] Predicting dose response to prostate cancer radiotherapy: validation of a radiation signature in the randomized phase III NRG/RTOG 0126 and SAKK 09/10 trials. Ann Oncol. 2025 May;36(5):572-582. doi: 10.1016/j.annonc.2025.01.017. PMID: 39986927

DOI

10.1016/j.annonc.2025.01.017

ISSN

1569-8041

PubMed ID

39986927