Background
Multicenter phase 3 trial; N=360 muscle-invasive bladder cancer post cystoscopic resection; radiotherapy with or without concurrent chemotherapy.
Interventions and follow up
Arm A: RT + chemo (5-FU 500 mg/m2 CIV d1–5 & d16–20; mitomycin C 12 mg/m2 d1)
Arm B: RT alone (55 Gy/20 fx over 4 wk or 64 Gy/32 fx over 6.5 wk)
Primary endpoint: Locoregional disease-free survival
Secondary: OS, adverse events
mFollow up: 69.9 mo
Arm B: RT alone (55 Gy/20 fx over 4 wk or 64 Gy/32 fx over 6.5 wk)
Primary endpoint: Locoregional disease-free survival
Secondary: OS, adverse events
mFollow up: 69.9 mo
Results
2yr locoregional DFS: 67% vs 54%, HR 0.68, 95% CI 0.48–0.96, P=.03.
5yr OS: 48% vs 35%, HR 0.82, 95% CI 0.63–1.09, P=.16 (NS).
5yr OS: 48% vs 35%, HR 0.82, 95% CI 0.63–1.09, P=.16 (NS).
Adverse events
Grade 3–4 overall (during treatment): 36% vs 27.5% (A vs B).
Genitourinary (G3–4): 21.3% vs 21.4%.
Gastrointestinal (G3–4): 9.6% vs 2.7%.
Genitourinary (G3–4): 21.3% vs 21.4%.
Gastrointestinal (G3–4): 9.6% vs 2.7%.
Conclusions
Synchronous 5-FU/mitomycin C with RT improves locoregional control of muscle-invasive bladder cancer vs RT alone, without significant increase in serious toxicity. Foundational evidence for chemoradiation bladder preservation.
Key Limitations
OS not significantly improved (trial not powered for it); 2x2 factorial design with concurrent RT-volume randomization; pre-modern era (no immunotherapy comparators); 5-FU/mitomycin radiosensitization less commonly used than gemcitabine or cisplatin-based regimens elsewhere.
Clinical Context
Established chemoradiation as a validated bladder-preservation strategy for muscle-invasive disease in patients unfit for or declining cystectomy. ESMO guidelines endorse trimodality therapy (maximal TURBT + concurrent chemoradiation) as an alternative to radical cystectomy in selected patients; 5-FU/mitomycin radiosensitization is a guideline-supported regimen.