Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial

Abstract

ObjectiveTo evaluate acute toxicity and quality of life (QOL) impact of ultra-hypofractionated whole pelvis radiotherapy (WPRT) compared to conventional WPRT fractionation post high-dose rate (HDR) prostate brachytherapy (BT). MethodsBLINDED FOR REVIEW is a phase 2, multi-institutional randomized controlled trial involving men with prostate-confined disease and NCCN unfavorable intermediate, high, or very-high-risk prostate cancer. Patients were randomly assigned to receive conventionally fractionated WPRT (standard arm) or ultra-hypofractionated WPRT (experimental arm) in a 1:1 ratio. All patients underwent radiotherapy with 15 Gy HDR-BT boost in a single fraction followed by WPRT delivered with conventional fractionation (45 Gy in 25 daily fractions or 46 Gy in 23 fractions) or ultra-hypofractionation (25 Gy in 5 fractions delivered on alternate days). Acute toxicities, measured during radiotherapy and at 6 weeks post-treatment, were assessed using the clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC-50) and International Prostate Symptom Score (IPSS). ResultsA total of 80 patients were enrolled and treated across three Canadian institutions. A total of 39 and 41 patients received external radiotherapy with conventionally fractionated and ultra-hypofractionated WPRT, respectively. All patients received androgen deprivation therapy, except for 2 patients treated in the ultra-hypofractionated arm. Baseline clinical characteristics were similar between the two arms, with 51 (63.8%) patients having high or very high-risk prostate cancer disease. Treatment was well tolerated with no significant differences in the rate of acute adverse events between arms. No grade 4 adverse events or treatment-related deaths were reported. Ultra-hypofractionated WPRT had a less detrimental impact in the EPIC-50 bowel total, function and bother domain scores when compared to conventional WPRT in the acute setting. On the contrary, more patients treated with ultra-hypofractionated WPRT reached the minimum clinical important difference on EPIC-50 urinary domains. No significant QOL differences between arms were noted in the sexual and hormonal domains. ConclusionUltra-hypofractionated WPRT following HDR-BT is a well-tolerated treatment strategy in the acute setting and leads to less detrimental impact on bowel QOL domains when compared to conventional WPRT.