Updated Toxicity and Quality-of-Life Outcomes From a Randomized Phase III Trial of Extreme Hypofractionated vs. Standard Fractionated Proton Therapy for Low-Risk Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> We present an interim analysis of toxicity and quality-of-life (QOL) from a randomized phase III trial of extreme hypofractionated versus standard hypofractionated proton therapy for low-risk prostate cancer. <h3>Materials/Methods</h3> From 2011-2020, low-risk prostate cancer patients were randomized in a 1:2 fashion to standard fractionation (79.2 Gy [RBE] in 44 fractions, Arm A) versus extreme hypofractionation (38 Gy [RBE] in 5 fractions, Arm B) proton therapy. Patients were excluded if they had an American Urological Association Symptom Index (AUASI) > 17. Toxicity was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and adjusted for pre-treatment toxicities. Patients completed Expanded Prostate Cancer Index Composite + (EPIC), Short Form 12 (SF) and AUASI surveys at baseline and 3, 6, 12, 18, 24 and 36 months. <h3>Results</h3> Forty-six patients were included in Arm A and 84 patients in Arm B. Median follow-up was 50 months. The majority of patients were clinical T1c (89% Arm A, 84.5% Arm B, <i>P</i> = 0.86) and a PSA > 4-10 (80.4% Arm A, 78.6% Arm B, <i>P</i> = 1.00). For both groups, median AUASI was 5 (range 0-14). Four patients (1 Arm A, 3 Arm B) had died at the time of last follow-up, none related to their prostate cancer or treatment. Between the two arms, no significant differences were noted in acute treatment-related genitourinary (GU) or gastrointestinal (GI) toxicities: acute GU grade ≥ 2 (0% Arm A, 5% Arm B), GU grade ≥ 3 (0% each arm), GI grade ≥ 2 (0% Arm A, 2% Arm B), grade ≥ 3 (0% each arm). Similarly, no significant differences were noted in late treatment-related GU or GI toxicities: late GU grade ≥ 2 (26% Arm A, 33% Arm B), GU grade ≥ 3 (2% Arm A, 1% Arm B), GI grade ≥ 2 (13% Arm A, 19% Arm B), GI grade ≥ 3 (0% each arm). When analyzing QOL by arm and timepoints, only EPIC Overall scores at 36 months were clinically significantly different (> MID) between the two arms with Arm B having improved scores (+29.62 points, <i>P</i> = 0.02). Other QOL domains (EPIC Urinary, EPIC Bowel, AUASI) were not clinically significantly different between the two arms across timepoints. <h3>Conclusion</h3> In a phase III randomized controlled trial comparing extreme hypofractionation to standard fractionation for the treatment of prostate cancer, no significant differences for treatment-related acute or late, grade ≥ 2 or ≥ 3, toxicity were found for GU or GI toxicities. Additionally, improved EPIC Overall scores at 36 months were found in patients treated with extreme hypofractionation. This trial was registered with Western IRB 20101536, and NCT01230866.