Patient Reported Outcomes and Early Toxicity from a Phase III Randomized Trial of Moderate vs. Ultrahypofractionated Radiation Therapy for Localized Prostate Cancer

Abstract

When compared to conventional fractionation, moderate hypofractionation (MHRT) for patients with localized prostate cancer affords improved patient convenience at the expense of a small increase in acute gastrointestinal (GI) toxicity, without compromising oncologic outcomes according to four recent randomized trials. With improved cost-effectiveness and a theoretical biological advantage, ultrahypofractionation (UHRT) is growing in interest. However, with limited randomized, prospective data to date, there is concern about comparative toxicity. We present an early analysis of the patient reported outcomes and early toxicity data of the first randomized clinical trial comparing MHRT to UHRT for men with low and intermediate risk prostate cancer. To determine differences in rates of acute toxicity and patient reported outcomes between MHRT and UHRT for localized prostate cancer. The Miami HEAT trial is an international, prospective randomized phase III non-inferiority trial in men with localized prostate cancer (cT1-T2N0M0, Gleason 6-7, PSA <20). Patients are randomly assigned (1:1) to MHRT consisting of 70.2Gy in 26 daily fractions using IMRT or UHRT consisting of 36.25Gy in 5 fractions. Short-term androgen deprivation therapy (4-6 months) is allowed for intermediate risk patients. Acute (<6 months) GI and genitourinary (GU) toxicity was assessed using CTCAE Version 4.0. A relative risk ratio was calculated for toxicity events with significance determined using Poisson regression. Patient reported outcomes were assessed using IPSS, EPIC SF-12, Max-PC, and EPIC urinary, bowel and sexual scales at baseline, 3 months post-treatment completion, and 9 months post-treatment completion. Between October 2013 and September 2019, 117 men were enrolled from 3 centers: 59 patients were randomly assigned to MHRT and 58 to UHRT. Median age was 62 years (range, 46-85 years). The majority had Gleason 7 (n=82, 70%) and intermediate risk disease (n=93, 79.5%). There was no significant difference in the demographic characteristics between the two arms. Median follow-up was 11.6 months (range, 8.2-21.1 months). Patients randomized to UHRT experienced fewer acute Grade 2 GU toxicity events (n=28 vs n=43); although, the difference was not statistically significant, RR=0.93 (95%CI=0.58 to 1.47; p=0.7496). Additionally, there was no statistically significant difference in terms of acute GI or GU toxicity between the two arms, RR=1.67 (95%CI=0.4 to 6.87; p=0.4843), or among any of the patient reported outcomes at any of the pre-specified time points. At this point, UHRT has not compromised acute GI or GU toxicity or any patient reported outcome when compared to MHRT in our trial. Early toxicity has been low in both arms. Further enrollment and follow-up is required to examine late side effects and primary tumor control.