RESUMEN
PURPOSE: We aimed to determine if ultra-hypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. MATERIALS AND METHODS: This study was a multicenter, randomized, controlled, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 according to AJCC 7th ed. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Non-inferiority for FFF was determined based on one-sided confidence intervals. Toxicities were compared at different time points using Fisher's Exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. RESULTS: Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR 3.9-5.2). The 2-year FFF was 100% for both groups, with the one-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI: -1.70%-6.96%), favoring the SBRT arm, thus fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. Rates of gastrointestinal (GI) and genitourinary (GU) G2 and G3 toxicities did not differ significantly between groups but the the study was not powered to detect significant toxicity differences. Also, HRQoL metrics did not differ significantly between groups over the study median follow up. CONCLUSIONS: SBPT is non-inferior to CFPT regarding FFF, with similar long-term GU and GI toxicity rates and minimal impact in patient reported HRQoL over time.