2 - Bladder Adjuvant Radiotherapy (BART): Clinical Outcomes from a Phase III Multicenter Randomized Controlled Trial
Presenter(s)
V. Murthy1, P. Maitre1, M. Pal1, R. Sharma2, L. Pujari3, D. Gudipudi2, D. M. Joseph4, B. Bandekar3, R. Krishnatry1, M. Singh1, P. Verma1, S. Kannan5, R. Phurailatpam6, A. Arora1, A. Joshi1, V. Noronha1, K. Prabhash1, S. Menon1, G. Bakshi1, and G. Prakash1; 1Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, 2Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India, 3Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Homi Bhabha National Institute, Varanasi, India, 4All India Institute of Medical Sciences, Dehradun, India, 5ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Navi Mumbai, India, 6ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
Purpose/Objective(s):
To report clinical outcomes from the multicenter phase III randomized trial of adjuvant radiotherapy (RT) after radical cystectomy (RC) and chemotherapy in locally advanced muscle-invasive bladder cancer (LA-MIBC).Materials/Methods:
Patients with high-risk (T3-4, N1-3, R+) non-metastatic urothelial MIBC post-RC were randomized 1:1 to adjuvant RT or observation (Obs), stratified by nodal stage (N0 vs N+) and chemotherapy (neoadjuvant/adjuvant/none). Cystectomy bed and pelvic nodes were treated with stoma-sparing RT to 50.4Gy in 28 fractions. Primary endpoint of 2-year locoregional failure-free survival (LRFS) and secondary endpoints of bladder cancer-specific survival (BCSS), disease-free survival (DFS), and overall survival (OS) were compared per protocol by log rank test. Competing risk analysis using Fine Gray model compared subdistribution hazard ratios (sHR) for LRFS (competing risks: distant metastases and non-cancer death) and DFS (competing risk: non-cancer death) between the two arms.Results:
Total 153 patients were randomized from 2016 to 2024 (RT = 77, Obs = 76). Overall, 62% patients had pT3-T4 and 41% had pN+ disease, and a variant histology component in 28% patients. Chemotherapy was neoadjuvant for 71% and adjuvant for 20% patients. No patients received immunotherapy. In RT arm, 63 received planned RT and 14 (defaulted/refused RT = 8, pre-RT progression =4, RT deemed unfeasible = 2) were analyzed with the Obs group (n=90). Over a median follow-up was 23 months (42 months for survivors), 37% patients had recurred, with 18% locoregional recurrences (RT 8% vs Obs 26%, p=0.006). Two-year LRFS was 65.3% (RT) vs 57.4% (Obs) (HR 0.74, 95% CI 0.46-1.19, p=0.22). Two-year DFS was 59.9% vs 52.8% (HR 0.74, 0.47-1.17, p=0.20), and BCSS was 77.6% vs 64.4% (HR 0.57, 0.31-1.07, p=0.07) respectively. RT showed significantly better LRFS (sHR 0.55, 0.31-0.97, p=0.04) and DFS (sHR 0.55, 0.32-0.95, p=0.03) in competing risk analysis. Overall, 45% patients died (31% due to disease, 14% other cause). Two-year OS was 68.1% (RT) vs 57.0% (Obs) (HR 0.80, 0.49-1.30, p=0.4). There were no isolated locoregional recurrences in the RT arm, with 2-year locoregional control 91.2% (RT) vs 76.4% (Obs) (HR 0.27, 0.10-0.71, p=0.004). Subgroup analysis showed significant benefit with RT in T3-T4 (sHR LRFS 0.40, DFS 0.42) and N+ disease (sHR LRFS 0.39, DFS 0.40). Late grade 3+ toxicity was similar (RT 8.5% RT vs Obs 10.5%, p=0.6).Conclusion:
Adjuvant RT improved LRFS and DFS without increased severe late toxicity in patients with LA-MIBC post cystectomy and chemotherapy. Potential benefit in OS is being explored in a planned individual patient data meta-analysis of randomized trials. Abstract 2 - Table 1: Patterns of failure (* with synchronous distant metastases)| Total | Obs | RT | p | |
| Cystectomy bed | 8.5% | 13.3% | 1.6%* | 0.01 |
| Regional | 15.7% | 21.1% | 7.9%* | 0.03 |
| Distant | 29.4% | 28.9% | 30.2% | 0.87 |
| Unknown | 0.6% | 1.1% | 0% |