The Bladder Adjuvant RadioTherapy (BART) trial, a phase III multicenter randomized study, has presented its findings on the acute and late toxicity of adjuvant radiotherapy (ART) in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. Presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting, the trial addresses long-term concerns about the safety of post-cystectomy radiotherapy, particularly regarding bowel toxicity.
The BART trial randomized 153 patients with high-risk MIBC to either adjuvant radiotherapy (50.4 Gy in 28 fractions) or observation. High-risk features included pT3-4 stage, pN1-3 stage, fewer than 10 lymph nodes removed, positive surgical margins, or downstaging from ≥cT3 with neoadjuvant chemotherapy. The primary endpoint was 2-year locoregional failure-free survival, with toxicity as a key secondary outcome.
Trial Design and Methodology
The radiotherapy protocol involved intensity-modulated, image-guided radiotherapy (IMRT + IGRT) with strict stoma sparing, bowel spill control, and a fraction size of 1.8 Gy. Contouring followed the 2016 IJROBP consensus guidelines, modifying the volume to include the cystectomy bed and common iliac nodes up to the aortic bifurcation. Researchers implemented multiple radiotherapy safety checkpoints to minimize bowel radiation doses.
Toxicity Outcomes
The toxicity analysis included 134 patients. Acute grade 2 toxicity, primarily bowel symptoms, was more common in the radiotherapy arm (17.5%) compared to the observation arm (1.4%, p<0.001). However, these symptoms were self-resolving and did not require surgical intervention or hospitalization. Grade 3 acute events were infrequent in the radiotherapy arm (1.6%) versus the observation arm (4.1%). Notably, 67% of patients receiving radiotherapy experienced no acute symptoms.
After a median follow-up of 27 months, late grade 2 adverse events were observed in 15% of radiotherapy-treated patients and 7% of patients in the observation arm. Grade 3/4 adverse events were less frequent in the radiotherapy arm (8.4%) compared to the observation arm (10.5%). Overall, 23.3% of radiotherapy-treated patients experienced late grade ≥2 toxicity events, compared to 17.5% of patients in the observation arm.
Multivariable analysis indicated that radiotherapy administration was significantly predictive of an increased risk of acute events (HR: 4.6, p=0.03).
Clinical Significance
Dr. Vedang Murthy, the study's lead author from Tata Memorial Centre, Mumbai, India, emphasized that this is the largest randomized controlled trial of adjuvant radiotherapy in bladder cancer. Strengths of the trial include its multicentric design, the high proportion of patients receiving systemic chemotherapy (90%), and adherence to consensus contouring guidelines. He also noted that the trial's follow-up for the primary endpoint of locoregional failure-free survival is ongoing, as is the collection of patient-reported outcome measures (PROM).
While the trial demonstrated that adjuvant radiotherapy is reasonably safe and tolerable, the oncological efficacy outcomes are still being assessed. The findings suggest that modern radiotherapy techniques can mitigate the risk of severe toxicity, potentially making ART a viable option for improving local control in high-risk MIBC patients. Further analyses are planned to assess patient-reported outcomes and quality of life domains.
