Phase II trial finds adding gemcitabine to cisplatin-radiotherapy does not improve 2-year disease-free survival in muscle-invasive bladder cancer

This Phase II randomized controlled trial compared organ preservation strategies in 69 patients with pT2-pT3N0M0 muscle-invasive bladder cancer after macroscopically complete transurethral resection. Patients were randomized to receive radiotherapy with cisplatin alone (n=24) or radiotherapy with cisplatin plus twice-weekly gemcitabine (n=45). The primary outcome was 2-year disease-free survival, which was similar between groups: 58.3% (95% CI 36.6-77.9) for cisplatin alone versus 60.0% (95% CI 44.3-74.3) for cisplatin plus gemcitabine. Median disease-free survival was 29.8 months versus 37.4 months, respectively, though statistical significance was not reported. Overall survival at 24 months was 91.3% versus 66.7%, and at 60 months was 66.8% versus 53.7%, with overlapping confidence intervals. Safety data showed comparable toxicity profiles between arms except for increased cytopenias in the gemcitabine-containing arm. Serious adverse events, discontinuation rates, and tolerability details were not reported. Key limitations include early study termination due to insufficient accrual, which limits statistical power and definitive conclusions. The small sample size and lack of reported p-values for several outcomes further constrain interpretation. For clinical practice, this evidence does not support adding twice-weekly gemcitabine to cisplatin-based chemoradiation to improve disease-free survival in this specific patient population. The findings highlight the need for larger, adequately powered trials to determine optimal chemoradiation regimens for bladder preservation.