Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial.

PURPOSE

We aimed to determine if ultrahypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is noninferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer.

METHODS AND MATERIALS

This study was a multicenter, randomized, controlled, noninferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, Prostate-specific antigen <10 ng/mL, and clinical stage T1-T2a N0 M0 according to 7th edition of the American Joint Committee on Cancer tumor-node-metastasis cancer staging system. 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. Noninferiority for FFF was determined based on 1-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 1-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI, -1.70% to 6.96%), favoring the SBRT arm, thus fulfilling the prespecified criteria for noninferiority of SBPT compared with CFPT. Rates of gastrointestinal and genitourinary G2 and G3 toxicities did not differ significantly between groups. Further, HRQoL metrics did not differ significantly between groups over the study's median follow-up.

CONCLUSIONS

SBPT is noninferior to CFPT regarding FFF, with similar long-term genitourinary and gastrointestinal toxicity rates and minimal impact in patient-reported HRQoL over time.