Multicenter evaluation of neoadjuvant and induction gemcitabine–carboplatin versus gemcitabine–cisplatin followed by radical cystectomy for muscle-invasive bladder cancer

Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine–carboplatin (gem–carbo) versus gemcitabine–cisplatin (gem–cis). Methods: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem–carbo or gem–cis followed by RC. Results: We included 747 patients treated with gem–carbo (n = 147) or gem–cis (n = 600). Patients treated with gem–carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem–carbo and gem–cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61–1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85–1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93–1.96]; p = 0.11). Median OS of patients treated with gem–carbo and gem–cis was 28.6 months (95%CI 18.1–39.1) and 45.1 months (95%CI 32.7–57.6) (p = 0.18), respectively. Median CSS of patients treated with gem–carbo and gem–cis was 28.8 months (95%CI 9.8–47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. Conclusion: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem–carbo and that survival outcomes seem comparable to gem–cis provided patients are able to receive ≥ 3 cycles and undergo RC.