Comparison of toxicities between ultrahypofractionated radiotherapy versus brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT +/- EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade >= 2 (8.6% at 5-years in UHF and 13.3% in BT +/- EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093-1.22, p = 0.2127). Actuarial grade >= 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774-7.383, p < 0.001) than in BT +/- EBRT (1.1%). In detailed subgroup analyses, the high-dose UHF group (H-UHF) using BED >= 226 Gy(1.5), showed higher GI toxicity profiles than the other subgroups (HDR + EBRT, LDR + EBRT, and LDR monotherapy, and L-UHF BED < 226 Gy(1.5)) with equivalent GU toxicity to other modalities. With a median follow-up period of 32 months and 75 months, the actuarial biochemical control rates were equivalent between the UHF and BT +/- EBRT groups. UHF showed equivalent efficacy, higher GI and equivalent GU accumulated toxicity to BT +/- EBRT, and the toxicity of UHF was largely dependent on the UHF schedule.