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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. [ABSTRACT FROM AUTHOR]

Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies. [ABSTRACT FROM AUTHOR]