Background
Multicenter, open-label, randomized phase 3 trial (Tata Memorial Centre, India) of adjuvant pelvic radiotherapy versus observation in 153 patients with nonmetastatic urothelial muscle-invasive bladder cancer (MIBC) at high risk after radical cystectomy (any of: pT3-4, N1-3, positive margin, or ≤10 nodes dissected). Over 90% received systemic chemotherapy (71% neoadjuvant, 20% adjuvant); none received immunotherapy.
Results
Interventions and follow up: Arm A: adjuvant stoma-sparing IG-IMRT, 50.4Gy in 28 fractions to the cystectomy bed and pelvic nodes
Arm B: observation
Primary endpoint: 2-year locoregional recurrence-free survival (LRFS)
mFollow up: 47mo
Results: 2-yr LRFS: 87.1% vs 76.0% (RT vs Obs); HR 0.43, 95%CI 0.20-0.96, P=.04
DFS: 71.6% vs 58.7%; HR 0.62, 95%CI 0.36-1.05
BCSS: 79.6% vs 65.0%; HR 0.59, 95%CI 0.33-1.10
OS: 70.4% vs 57.4%; HR 0.78, 95%CI 0.49-1.26
Arm B: observation
Primary endpoint: 2-year locoregional recurrence-free survival (LRFS)
mFollow up: 47mo
Results: 2-yr LRFS: 87.1% vs 76.0% (RT vs Obs); HR 0.43, 95%CI 0.20-0.96, P=.04
DFS: 71.6% vs 58.7%; HR 0.62, 95%CI 0.36-1.05
BCSS: 79.6% vs 65.0%; HR 0.59, 95%CI 0.33-1.10
OS: 70.4% vs 57.4%; HR 0.78, 95%CI 0.49-1.26
Adverse events
Severe toxicity: no additional severe toxicity with adjuvant RT versus observation (per authors)
Grade ≥3 GI/GU (specific rates): NR in primary report
Grade ≥3 GI/GU (specific rates): NR in primary report
Conclusions
Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy significantly improved 2-year locoregional control (primary endpoint met; HR 0.43) in high-risk urothelial MIBC, with numerically favorable but non-significant gains in DFS, BCSS, and OS, and no additional severe toxicity. The trial supports adjuvant RT as an option for locoregional control in selected high-risk patients but does not establish a survival benefit.
Key Limitations
Small trial (N=153) underpowered for survival endpoints (DFS, BCSS, OS all non-significant); the primary endpoint (LRFS) is a locoregional surrogate rather than survival; open-label; no patient received adjuvant immunotherapy, so the control arm does not reflect current systemic standard of care; predominantly single-network Indian population limits generalizability.
Clinical Context
Adjuvant RT after cystectomy has historically been used sparingly owing to toxicity concerns and scarce randomized data. Since CheckMate-274, adjuvant nivolumab is FDA-approved for high-risk MIBC after cystectomy. This trial revives adjuvant pelvic RT specifically for locoregional control. There is no regulatory action for RT in this setting; NCCN lists adjuvant RT as a consideration for adverse pathologic features (e.g., pT3-4, positive margins) at a lower evidence tier, and ESMO does not routinely recommend it. Findings may inform selective use for locoregional control alongside, not in place of, systemic therapy.