Background
Pooled individual-patient analysis of 6 RTOG bladder-preserving trials (protocols 8802, 8903, 9506, 9706, 9906, and 0233). 468 patients with cT2–T4a muscle-invasive bladder cancer eligible for selective bladder-preservation trimodality therapy (TURBT + concurrent chemoRT). Median follow-up 4.3 years from study entry.
Interventions and follow up
Arm A: Trimodality therapy across 6 RTOG protocols — maximal TURBT followed by induction CRT (cisplatin-based ± other agents, 40 Gy), then consolidation CRT (64–65 Gy total) for complete responder
Arm B: N/A (single-arm pooled analysis)
Primary endpoint: Overall survival, disease-specific survival, bladder-intact survival, and locoregional control
mFollow up: 4.3 year
Arm B: N/A (single-arm pooled analysis)
Primary endpoint: Overall survival, disease-specific survival, bladder-intact survival, and locoregional control
mFollow up: 4.3 year
Results
5-yr OS: 57%
10-yr OS: 36%
5-yr disease-specific survival: 71%
5-yr intact bladder survival: 45%
Complete response to induction CRT: 72%
Late grade ≥3 GU toxicity: 5.7%
Late grade ≥3 GI toxicity: 1.9%
10-yr OS: 36%
5-yr disease-specific survival: 71%
5-yr intact bladder survival: 45%
Complete response to induction CRT: 72%
Late grade ≥3 GU toxicity: 5.7%
Late grade ≥3 GI toxicity: 1.9%
Adverse events
Main adverse events: Late grade ≥3 GU toxicity 5.7%; late grade ≥3 GI toxicity 1.9%. No significant increase in bowel or bladder toxicity over time. Toxicity was acceptable across all 6 protocols.
Conclusions
Pooled RTOG data confirm that long-term OS and disease-specific survival with bladder-preserving TMT are comparable to published radical cystectomy series. Complete response to induction CRT predicts superior intact bladder survival. The low rate of late severe GU/GI toxicity supports excellent quality of life for long-term survivors.
Key Limitations
Key Limitations: Pooled analysis of heterogeneous protocols spanning nearly two decades with evolving CRT regimens and RT techniques. No contemporaneous cystectomy control arm. Inclusion criteria across protocols varied; pooling may obscure differences in outcomes by era. Median follow-up of 4.3 years may underestimate late recurrence rates.
Clinical Context
This RTOG pooled analysis is the most comprehensive multi-institutional dataset supporting TMT for MIBC, complementing the MGH series and BC-2001. Cited in NCCN, EAU, and AUA/ASTRO/ASCO bladder cancer guidelines as key evidence for bladder preservation as a curative-intent alternative to cystectomy in appropriately selected patients.
References
References: Mak RH et al, JCO 2014; PMID: 25366678