Pelvic nodes ultra-hypo fractionated versus conventionally fractionated IMRT with HDR brachytherapy in prostate cancer: interim analysis of a collaborative multi-institutional non-inferiority phase 3 trial (PCS-XI, NCT05820633).

Abstract

Ultra-hypofractionation (UHF) has emerged as a safe and effective strategy; however, its role in prostate cancer (PCa) pelvic nodal irradiation combined with high-dose-rate brachytherapy (HDR-BT) and androgen deprivation therapy (ADT) remains insufficiently defined. PCS-XI (NCT05820633) is a multicentre, phase III randomized trial evaluating pelvic UHF versus conventionally fractionated (CF) radiotherapy. We report a prespecified interim analysis focusing on toxicity and patient-reported outcomes (PROs). Men with unfavorable-intermediate to very-high-risk prostate adenocarcinoma were enrolled. Patients were randomized 1:1 to CF (43 Gy/20 fractions, 44 Gy/22 fractions, or 46 Gy/23 fractions) or UHF (25 Gy in 5 fractions delivered every other day) whole pelvis radiotherapy, combined with single-fraction 15 Gy HDR-BT to the prostate with concomitant ADT. Genitourinary and gastrointestinal toxicities (CTCAE v5.0) and PROs (IPSS, SHIM, EPIC-26) were collected longitudinally. At interim analysis, 142 patients were randomized (CF = 73; UHF = 69), with a median follow-up of 17.6 months. Baseline clinicopathologic characteristics, ADT exposure, and treatment volumes were well balanced between arms. Grade 2-3 GU and GI toxicity rates were low and comparable between arms. No grade 4-5 toxicities were observed. Longitudinal PRO analyses demonstrated parallel trajectories. Clinically meaningful differences favoring UHF were observed for urinary incontinence at 12 months and bowel function at 18 months. Conversely, the CF arm demonstrated superior early hormonal function at 3 and 9 months. Pelvic UHF combined with HDR-BT and ADT was well tolerated compared to CF. These findings support its short-term safety and tolerability. Longer follow-up is required to prove non-inferiority and assess oncologic outcomes.