Adjuvant chemotherapy in muscle-invasive bladder carcinoma: a pooled analysis from phase III studies.

Background: The treatment of muscle-invasive bladder carcinoma should include both the eradication of local disease and the elimination of potential micrometastases. To date, the 'gold standard' treatment for muscle invasive bladder carcinoma has been recognized to be radical cystectomy. Adjuvant chemotherapy (AC) has the advantage of being administered to patients with known prognostic factors of recurrence. A pooled analysis was used to verify whether AC is able to increase the disease-free survival (DFS) and overall survival (OS) of patients with muscle-invasive bladder carcinoma who had undergone radical cystectomy.

Methods: All published randomized Phase III studies were considered eligible and a literature-based pooled analysis was accomplished. DFS and OS were the endpoints. Event-based relative risk ratio (RR) and 95% confidence intervals (95% CI) were derived. Combined effect estimation was computed with a fixed- and a random-effect model. A heterogeneity test was applied as well.

Results: Five trials were collected. All were evaluable for OS (350 patients) and four of these also were evaluable for DFS (273 patients). A significant benefit from AC was noted both in OS (RR, 0.74; 95% CI, 0.62-0.88 [P = 0.001]) and DFS (RR, 0.65; CI 0.54-0.78, [P < 0.001]). No significant heterogeneity was found.

Conclusions: Although the results of the analysis favor the use of AC, larger studies are needed to identify the role of AC in the treatment of muscle-invasive bladder carcinoma. Ongoing trials (European Organization for Research and Treatment of Cancer [EORTC]/Southwest Oncology Group [SWOG] and the Italian Multicentric Study) can help to better identify patients who can benefit from this approach.