Long-term Outcomes of Toxicities and Disease Control Following Postoperative Moderately Hypofractionated Radiotherapy in High-Risk Prostate Cancer: Results of a Prospective Study

Background: Moderately hypofractionated radiation therapy (MHRT) offers practical advantages for postoperative prostate cancer (PC) patients.However, concerns persist regarding long-term genitourinary (GU) toxicity.This prospective cohort study aims to evaluate late toxicities, disease control outcomes, and to identify predictors of late GU toxicity following MHRT. Methods:We prospectively enrolled 278 PC patients treated with postoperative MHRT (62.75 Gy delivered in 25 fractions) at our institution from 2018 to 2020.Late GU and gastrointestinal (GI) toxicities were graded using CTCAE v.4.0.Clinical outcomes were analyzed, including event-free survival (EFS), biochemical progression-free survival (bPFS), disease-specific survival (DSS), and overall survival (OS).Univariate and multivariate Cox regression analyses were performed to identify predictors associated with late GU toxicity. Results:The median follow-up was 50 months.The cumulative incidence of late grade 2 GU toxicity at 2 and 4 years was 19.5% and 28.4%, respectively.Patients with bladder V 60Gy >12.35% had a significantly higher 4-year incidence of late grade 2 hematuria (16.3% vs. 6.8%,p = 0.020).Furthermore, the 4-year cumulative incidence of late grade 2 urinary incontinence (UI) was higher in patients with preRT grade 2-3 incontinence (31.2% vs. 19.1%,p = 0.025).Among 40 patients undergoing postRT cystoscopy, these patients experienced significant higher rates of grade 2 UI than those not undergoing cystoscopy (45.0% vs. 17.5%, p < 0.001).Late grade 2 GI toxicity only occurred in 4 (1.4%) patients.The 4-year EFS, bPFS, DSS, and OS were 81.0%, 86.9%, 99.6% and 97.2%, respectively. Conclusions:Postoperative MHRT for PC demonstrates acceptable toxicity and promising efficacy.However, late GU toxicities continue to evolve beyond the 2-year period.Our findings identify key predictors: limiting bladder V 60Gy may mitigate hematuria, and preRT incontinence predicts worsening UI.