Systemic chemotherapy for advanced bladder cancer: update and controversies.

Despite improvements in surgical techniques and outcomes, 5-year survival rates for patients with muscle-invasive bladder cancer remain suboptimal. Almost 50% of patients will eventually progress and develop systemic disease. Although various single agents have shown activity in patients with advanced or metastatic disease, randomized trials have demonstrated the utility of cisplatin-based combinations regimens. Despite relatively high objective response rates, the impact on survival in patients with advanced disease has been quite limited. Surgical resection in selected patients achieving significant objective response to cytotoxic therapy can contribute to long-term survival rates. The role of salvage therapy in advanced disease remains undefined. Evaluation of several active compounds has yielded unimpressive results with low objective response rates and overlapping CIs. Recognition that the maximum benefit from conventional cytotoxics has been achieved has led to the recent initiation of a number of clinical trials evaluating targeted agents in the management of advanced urothelial cancer.