Multicenter phase 3 trial of adjuvant radiotherapy versus observation after chemotherapy and cystectomy for muscle-invasive bladder cancer

A multicenter phase 3 trial in India evaluated adjuvant radiotherapy (RT) versus observation (Obs) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC). The trial included 153 patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, ≤ 10 nodes dissected), who were randomized 1:1 to adjuvant RT (n=77) or Obs (n=76), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IMRT 50.4 Gy in 28 fractions was presecribed to the cystectomy bed and pelvic nodes. The primary endpoint was 2-year locoregional recurrence-free survival (LRFS) rate; secondary endpoints were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS). At a median follow-up of 47 months, the 2-year LRFS rate was 87.1% with RT versus 76.0% with Obs (HR 0.43; 95% CI 0.20-0.96), the 2-year DFS rate was 71.6% versus 58.7% (0.62; 0.36-1.05), the 2-years BCSS rate was 79.6% versus 65.0% (0.59; 0.33-1.10), and 2-year OS rate was 70.4% versus 57.4% (0.78; 0.49-1.26). The authors conclude that adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy was associated with improved locoregional control in patients with high-risk urothelial MIBC, without additional severe toxicity.