Bladder Adjuvant Radiation Therapy (BART): Acute and Late Toxicity From a Phase III Multicenter Randomized Controlled Trial

Int J Radiat Oncol Biol Phys. 2024 Sep 29:S0360-3016(24)03411-4. doi: 10.1016/j.ijrobp.2024.09.040. Online ahead of print.

Abstract

Purpose: To report toxicity from the multicenter phase III randomized trial of Bladder Adjuvant Radiation Therapy (BART) after radical cystectomy and chemotherapy in high-risk muscle-invasive bladder cancer (MIBC).

Methods and materials: Patients with nonmetastatic urothelial MIBC with ≥1 high-risk feature after radical cystectomy- pT3-4, pN1-3, nodal yield <10, positive margin, or ≥cT3 downstaged with neoadjuvant chemotherapy- were randomized 1:1 to observation (Obs) or adjuvant radiation therapy (RT) at 4 centers, stratified by pN stage (N0, N+) and chemotherapy (neoadjuvant, adjuvant, none). Stoma-sparing image guided intensity modulated RT 50.4 Gy in 28# was prescribed to the cystectomy bed and pelvic nodes. Acute toxicity (≤3 months of RT/randomization) and late toxicity were assessed per protocol using Common Terminology Criteria for Adverse Event v5.0. Patients progressing within 3 or 6 months of randomization were excluded from acute or late toxicity analysis, respectively.

Results: The BART trial enrolled 153 patients (Obs = 76, RT = 77). About half (49%) had pN+. Nearly 90% received chemotherapy (70% neoadjuvant; most commonly gemcitabine plus cisplatin). In the RT arm, 63/77 completed RT per protocol with no toxicity-related RT termination. Of the 134 patients analyzable for acute toxicity, no difference was observed in grade 3 (Obs 4.2% vs RT 1.6%, P = .34). Grade 2 effects were higher with RT (17.5% vs 1.1%, P < .001), mainly diarrhea/enteritis or proctitis. Late toxicity was analyzable for 104 patients (Obs = 57, RT = 47) with a median follow-up of 27 months. Grades 3 to 4 toxicity were about 10% (Obs 10.5% vs RT 8.4%, P = .62), and cumulative late grade 2+ toxicity was similar in both groups (17.5% vs 23.3%, P = .27).

Conclusions: In the largest trial of adjuvant RT for high-risk urothelial MIBC, severe acute and late toxicity were low and similar with obervation or radiation therapy. The oncological outcomes are awaited.