Consideration of Patient Characteristics and Comorbidity in Selecting Candidates for Moderately Hypofractionated Radiation: Secondary Analysis From a Randomized Trial

Abstract

Randomized trials demonstrate prostate radiation delivered with moderate hypofractionation provides cancer control equivalent to conventional fractionation. While trials demonstrate similar genitourinary (GU) and gastrointestinal (GI) toxicity between treatments, it is uncertain if patients with significant comorbidities, on anticoagulants, or who are older may be at increased risk of toxicity after moderate hypofractionation. Men with localized prostate cancer enrolled in a randomized trial received either conventionally fractionated IMRT (CIMRT; 75.6 Gy in 1.8 Gy fractions) or dose-escalated hypofractionated IMRT (HIMRT; 72 Gy in 2.4 Gy fractions). Late (>= 60 days after IMRT) GI and GU toxicities were prospectively evaluated and scored by modified RTOG criteria. The adult comorbidity evaluation-27 (ACE-27) index categorized severity of comorbidity. Cox proportional hazard models were used for statistical analysis. One hundred one men received CIMRT and 102 HIMRT. The median follow-up was 8.6 years. Eighty-two men were >=70 years, 59 were on anticoagulants at enrollment, and 39 had moderate to severe comorbidity (ACE-27 2-3). Overall, there was no difference in late GU toxicity between treatment arms (P = 0.84, HR = 0.93) and a numeric increase in late GI toxicity after HIMRT (P = 0.09, HR = 2.50). For all patients, anti-coagulation use (P = 0.05, HR = 1.40) trended towards worse late GI toxicity. However, in the subset of men on anticoagulants, there was no difference in GI (P = 0.51) or GU (P = 0.38) toxicity between those treated with CIMRT and HIMRT. Similarly in the subset of men with moderate to severe comorbidity (GI: P = 0.08; GU: P = 0.22) and the subset of men >= 70 years (GI: P = 0.18; GU: P = 0.09), there was no difference in toxicity between treatment arms. On multivariate analysis of men treated with HIMRT, higher rectal dose was associated with worse late GI toxicity (P = 0.03, HR = 1.18), however, there was no increase in late GI or GU toxicity with anticoagulation use (GI: P = 0.30; GU: P = 0.79) or older age (GI: P = 0.13; GU: P = 0.38). Late GI and GU toxicity was not significantly increased in older men, those on anticoagulants, or those with moderate to severe comorbidity when treated with HIMRT on a randomized trial. Therefore, men with these characteristics can be considered for moderately hypofractionated prostate radiation as definitive therapy.