A robustness-inclusive comparison of proton- versus photon-based whole-pelvic radiotherapy for prostate cancer within a randomised clinical trial
Sofie Tilbæk et al.
The article evaluates whether proton therapy can provide superior organ protection while maintaining treatment robustness in patients with high-risk prostate cancer receiving whole-pelvic radiotherapy (WPRT). The study was conducted within a multicenter randomized clinical trial framework and focused particularly on the impact of anatomical and setup variations during treatment, which are known challenges in proton therapy.
The researchers analyzed treatment plans from five prostate cancer patients treated at a national proton therapy center. For comparison, five photon therapy centers independently generated photon-based plans for the same patients. Both proton and photon plans were assessed under nominal conditions, recalculated using repeat CT scans, and tested with robustness scenarios simulating geometric uncertainties and inter-fractional anatomical changes. Dose-volume metrics for target coverage and organs at risk, including bowel and bladder, were compared using statistical models that accounted for variability between patients and centers.
The results demonstrated that both proton and photon therapies achieved robust and reliable target coverage across all evaluated scenarios. However, proton therapy significantly reduced radiation exposure to healthy tissues, particularly in the low- and intermediate-dose ranges. The bowel V35Gy was reduced by 11.2 percentage points, while the bowel mean dose decreased by 13.9 Gy. Additionally, the bladder mean dose was reduced by 18.4 Gy compared with photon therapy. Importantly, these dosimetric advantages remained stable even when anatomical variations and treatment uncertainties were considered.
In conclusion, the study suggests that proton-based WPRT offers meaningful reductions in radiation dose to surrounding healthy tissues without compromising treatment robustness or target coverage. These findings support the potential clinical benefit of proton therapy for high-risk prostate cancer patients, particularly in minimizing gastrointestinal and bladder toxicity while maintaining effective radiotherapy delivery.
Published by Radiotherapy and Oncology 217 (2026)
