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
Date
02/23/2025Pubmed ID
39986927Pubmed Central ID
PMC12034480DOI
10.1016/j.annonc.2025.01.017Scopus ID
2-s2.0-85219073953 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Dal Pra A, Ghadjar P, Ryu HM, Proudfoot JA, Hayoz S, Michalski JM, Spratt DE, Liu Y, Schär C, Berlin AM, Zwahlen DR, Simko JP, Hölscher T, Efstathiou JA, Polat B, Sandler HM, Hildebrandt G, Parliament MB, Mueller AC, Dayes IS, Plasswilm L, Correa RJM, Robertson JM, Karrison TG, Davicioni E, Hall WA, Feng FY, Pollack A, Thalmann GN, Nguyen PL, Aebersold DM, Tran PT, Zhao SGAuthor
William Adrian Hall MD Chair, Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedDose-Response Relationship, Radiation
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Prognosis
Prostatectomy
Prostatic Neoplasms
Radiotherapy Dosage
Salvage Therapy
