Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

PurposeCisplatin-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% 88 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 91 [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. 4 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.