Hypofractionated Radiotherapy for Prostate Cancer: A Comparative Study of Clinical Outcomes and Dosimetry Between Proton and Photon Therapy

Chun-Te Wu,1 Wen-Cheng Chen,2 Yao-Yu Wu,3 Miao-Fen Chen3 1Department of Urology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan; 3Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Miao-Fen Chen, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Email [email protected]: Hypofractionated radiation therapy (HFRT) is increasingly accepted for prostate cancer. This prospective study compared clinical outcomes, early prostate-specific antigen (PSA) dynamics, and dosimetry between proton and photon HFRT for high-risk prostate cancer.Methods: A total of 118 patients with high-risk prostate cancer were treated with HFRT (70Gy in 28 fractions) between 2022– 2024, receiving either intensity-modulated proton therapy (IMPT, n = 36) or photon therapy (VMAT, n = 82). All patients received long-term androgen deprivation therapy (ADT). Primary endpoints included biochemical control, PSA nadir at 6 months post-treatment, and genitourinary (GU) and gastrointestinal (GI) toxicities. Dosimetric comparisons were performed in silico.Results: While biochemical control rates were comparable, a significantly higher proportion of patients receiving proton therapy achieved a PSA nadir < 0.1 ng/mL within 6 months. Proton therapy was associated with reduced GU toxicity compared to photon therapy, based on assessments from both physicians and patients. Dosimetric analysis confirmed that proton therapy provided excellent target coverage with superior organ-at risk (bladder and rectum) sparing. We further identified dosimetric parameter to determine the cuff-off value for GU events. The data revealed the percentage volume of bladder receiving ≥ 90% prescribed dose (V90%) ≥ 11% has the predictive value for the development of grade ≥ 2 genitourinary toxicity.Conclusion: Two-year biochemical control was comparable between proton- and photon- based HFRT in high-risk prostate cancer. Proton therapy demonstrated improved early PSA kinetics and reduced GU toxicity, supported by favorable dosimetric profiles. The identification of bladder V90% < 11% as a planning constraint may guide treatment optimization. Further studies with longer follow-up are warranted to validate these benefits.Keywords: prostate cancer, hypofractionated radiotherapy, proton therapy