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).
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.
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.
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.
Annals of oncology : official journal of the European Society for Medical Oncology. 2025 Feb 13 [Epub ahead of print]
A Dal Pra, P Ghadjar, H M Ryu, J A Proudfoot, S Hayoz, J M Michalski, D E Spratt, Y Liu, C Schär, A M Berlin, D R Zwahlen, J P Simko, T Hölscher, J A Efstathiou, B Polat, H M Sandler, G Hildebrandt, M B Parliament, A-C Mueller, I S Dayes, L Plasswilm, R J M Correa, J M Robertson, T G Karrison, E Davicioni, W A Hall, F Y Feng, A Pollack, G N Thalmann, P L Nguyen, D M Aebersold, P T Tran, S G Zhao
Department of Radiation Oncology, University of Miami/Sylvester Comprehensive Cancer Center, Miami, USA. Electronic address: ., Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany., Veracyte Inc., San Diego, USA., SAKK Coordinating Center, Bern, Switzerland., Washington University School of Medicine, Saint Louis, USA., University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, USA., University Health Network-Princess Margaret Hospital, Toronto, Canada., Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., University of California San Francisco, San Francisco, USA., Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany., Massachusetts General Hospital Cancer Center, Boston, USA., Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg, Germany., Cedars-Sinai Medical Center, Los Angeles, USA., Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany., University of Alberta, Edmonton, Canada., Department of Radiation Oncology, Eberhard Karls University, Tübingen, Germany., Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Canada., Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland., London Health Sciences Centre, London, Canada., William Beaumont Hospital, Royal Oak, USA., NRG Oncology Statistics and Data Management Center, Philadelphia, USA., Medical College of Wisconsin, Milwaukee, USA., Department of Radiation Oncology, University of Miami/Sylvester Comprehensive Cancer Center, Miami, USA., Department of Urology, Bern University Hospital, Bern, Switzerland., Dana Farber Cancer Institute, Boston, USA., Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland., Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, USA. Electronic address: ., Department of Human Oncology, University of Wisconsin, Madison, USA. Electronic address: .