Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.

PURPOSE: To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC).

METHODS

Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, ≤10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS).

RESULTS

From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively.

CONCLUSION

Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.