Neoadjuvant Chemotherapy for Transitional Cell Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

Abstract

PURPOSE: Despite local therapy most patients with muscle invasive transitional cell carcinoma (TCC) of the bladder die of systemic relapse, indicating a need for effective adjunctive systemic treatment. We determined whether neoadjuvant chemotherapy improved overall survival. MATERIALS AND METHODS: A systematic review and meta-analysis were performed of all known randomized controlled trials (RCTs) of neoadjuvant chemotherapy for stages II and III TCC conducted between 1984 and 2002. RESULTS: A total of 16 eligible RCTs (3,315 patients) were identified. Of these trials 11 (2,605 patients) provided data suitable for a meta-analysis of overall survival and the pooled HR was 0.90 (95% CI 0.82 to 0.99, p = 0.02). Eight trials used cisplatin based combination chemotherapy and the pooled HR was 0.87 (95% CI 0.78 to 0.96, p = 0.006), consistent with an absolute overall survival benefit of 6.5% (95% CI 2 to 11%) from 50% to 56.5%. Reported progression-free survival data were insufficient for meta-analysis but they appeared concordant with overall survival results. Mortality due to combination chemotherapy was 1.1%. A major pathological response was associated with improved overall survival in 4 trials. CONCLUSIONS Neoadjuvant cisplatin based chemotherapy improves overall survival in muscle invasive TCC. The size of the effect is modest and combination chemotherapy can be administered safely without adverse outcomes resulting in delayed local therapy. An optimal chemotherapy regimen was not identified and newer regimens have not been tested in RCTs in this setting. Further efforts to identify the patients most likely to benefit from neoadjuvant therapy are necessary to optimize its use.