Neoadjuvant Cisplatin-based Chemotherapy in Nonmetastatic Muscle-invasive Bladder Cancer: A Systematic Review and Pooled Meta-analysis to Determine the Preferred Regimen.

ABSTRACT

OBJECTIVE: To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity. MATERIALS AND METHODS: This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively. RESULTS: Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies. CONCLUSION: Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.