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
Menée à partir de l'analyse de 226 215 échantillons tissulaires et à partir d'une série de données en vie réelle portant sur 42 407 prostatectomies et 31 107 échantillons biopsiques, cette étude évalue la performance d'un système de score postopératoire pour identifier les patients pouvant bénéficier d'une escalade de dose de rayonnements ionisants
Background : The SAKK 09/10 trial randomized biochemically-recurrent prostate cancer patients to salvage radiation 64Gy vs. 70Gy, and the NRG/RTOG 0126 randomized intermediate-risk prostate cancer patients to definitive radiation 70.2Gy vs. 79.2Gy. We investigated a previously developed Post-Operative Radiation Therapy Outcomes Score (PORTOS) to identify preferential benefit from radiation dose escalation (DE).
Methods : PORTOS was evaluated in patients enrolled on 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 RTOG 0126 as cutoffs 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 vs. higher) and treatment arm for Clinical Progression Free Survival. Only patients in the higher PORTOS score group benefited from DE. In NRG/RTOG 0126, in patients with lower tertile PORTOS scores, there was no difference in Phoenix Biochemical Failure (BF). However, for patients in the average and higher tertile PORTOS score 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 clinicopathologic 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 clinicopathologic or prognostic variables. These results suggest that PORTOS could be used clinically as a predictor of radiation response.
Annals of Oncology , résumé, 2025