Twice- vs. thrice-weekly moderate hypofractionated radiotherapy for prostate cancer: does overall treatment time matter?

Abstract

To evaluate the influence of overall treatment time (OTT) in disease control, acute, and long-term side effects with moderate hypofractionated external beam radiotherapy (RT) for prostate cancer (PCa) delivered either twice- or thrice-a-week. 157 patients with localized PCa were treated consecutively with 56Gy in 4Gy/fraction delivered either twice (86 patients, from 2003 to 2010, group-1) or thrice a week (71 patients, from 2010 to 2017, group-2) using IMRT or VMAT techniques. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the CTCAE v3.0 grading scale. Median follow-up was 110 and 56months for groups 1 and 2, respectively. At 6weeks, patients treated thrice-a-week experienced higher acute ≥ grade-2 GU toxicity compared to those treated twice a week (25.4% vs 5.8%, p = 0.001) even though none presented ≥ grade-3 GU or GI toxicity in the thrice-a-week group. The 5-year ≥ grade-2 late GU toxicity-free survival was higher in group-1 (95.9 ± 2.3%) than in group-2 (81.5 ± 4.9%, p = 0.003), while no differences in ≥ grade-2 late GI toxicity-free survival were observed between both groups (97.5 ± 1.7% vs. 97 ± 2.1% for groups 1 and 2, respectively). The 5-year biochemical relapse-free survival (bRFS) was not different for patients treated twice compared to those treated thrice-a-week (80.6 ± 4.5% vs. 85.3 ± 4.8%, respectively, p = 0.441), as much as for patients treated in > 5weeks vs. those treated in ≤ 5weeks (81.3 ± 4.4% vs. 84.4 ± 5.1%, respectively, p = 0.584). In this retrospective hypothesis-generating analysis, less vs. more than 5weeks OTT may increase acute and late GU toxicities without significantly improving bRFS in patients treated to high effective doses (> 80Gy) with moderate hypofractionated RT. Prospective trials evaluating the impact of OTT on hypofractionated schedules for PCa are warranted.