Neoadjuvant cisplatin-based chemotherapy in nonmetastatic muscle-invasive bladder cancer: A systematic review and pooled meta-analysis to determine the preferred regimen.

OBJECTIVE: To determine whether neoadjuvant gemcitabine and cisplatin (GC) versus 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 (MIBC) with secondary analyses of pathological downstaging and toxicity.

MATERIALS AND METHODS: This systematic review and meta-analysis identified studies of patients with MIBC 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 (OR) 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% CI 0.56; 0.90]), PFS (HR 0.76 [95% CI 0.60; 0.97]), and pathological downstaging (OR 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.

CONCLUSIONS: Neoadjuvant ddMVAC is associated with improved overall survival and progression-free survival versus gemcitabine/cisplatin for patients with muscle-invasive bladder cancer prior to radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with overall survival. Dose-dense MVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.