Randomized Phase III Study of Moderately Hypofractionated Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Adenocarcinoma of the Prostate: Analysis of Quality of Life and Toxicity, PCG GU 003.

PURPOSE/OBJECTIVE(S) To report the analysis on the quality of life (QOL) and toxicity in intermediate-risk prostate cancer patients treated with or without androgen deprivation therapy (ADT) on PCG GU 003. MATERIALS/METHODS Between 2012 and 2019, intermediate-risk prostate cancer patients were enrolled. Patients were randomized to receive moderately hypofractionated proton beam therapy (PBT) to 70 Gy relative biologic effectiveness (RBE) in 28 fractions to the prostate with or without 6 months of ADT. ADT was started 2 months prior to radiation and consisted of luteinizing hormone-releasing hormone (LHRH) agonists. Expanded Prostate Cancer Index Composite (EPIC), Short-Form 12, and the American Urological Association Symptom Index (AUASI) instruments were given at baseline, 3, 6, 12, 18, and 24 months after PBT. Toxicities were assessed according to Common Terminology Criteria for Adverse Events (Version 4). Clinically significant differences for EPIC domains were 6-9 points for urinary incontinence, 5-7 points for urinary irritative, 4-6 points for bowel, 10-12 points for sexual, and 4-6 points for hormonal. RESULTS One hundred ten patients were randomized to PBT either with 6 months of ADT (n = 55) or without ADT (n = 55). Median follow-up was 32.4 months (range, 5.5-84.6). Patient and tumor characteristics were similar between arms with most patients being T1c (59.1%), Gleason 3+4 (62.7%) and PSA < 10 (79.1%). Baseline median AUASI was also similar (6 ADT vs 5 no ADT, P = 0.359). Acute and late grade 2+ genitourinary (GU) toxicity was similar between arms (acute 7.3% ADT vs 1.8% no ADT, P = 0.363; late 30.9% ADT vs 16.4% no ADT, P = 0.115). Acute and late grade 2+ gastrointestinal (GI) toxicity was similar between arms (acute 1.8% ADT vs 0% no ADT, P = 1; late 10.9% ADT vs 10.9% no ADT, P = 1). The only grade 3+ toxicities were in the ADT arm and consisted of 1 patient (1.8%) with an acute grade 3 GI and 1 patient (1.8%) with a late grade 3 GU toxicity. The ADT arm experienced worse overall QOL in the sexual (-16.1, P < 0.001) and hormonal (-6.3, P < 0.001) domains, with the largest time-specific hormonal differences at 3 (-13.8, P < 0.001) and 6 (-11.2, P < 0.001) months. However, there were no clinically significant differences 6 months after PBT. There were no clinically significant differences in AUASI, urinary incontinence, urinary irritative, or bowel domains. CONCLUSION Low acute and late toxicity rates were seen in both arms of the trial. Omitting ADT resulted in clinically significant improvement in hormonal and sexual QOL, typically resolving within 12 months after PBT.