Second-line systemic therapy for metastatic urothelial carcinoma of the bladder.

While platinum-based combination chemotherapy leads to high response rates in patients with advanced urothelial cancer of the bladder, most patients will ultimately progress and optimal treatment in the second-line setting still needs to be determined. Advanced age, poor performance status, comorbidities and rapidly progressive disease have rendered accrual into trials difficult. Vinflunine is the only cytotoxic agent to demonstrate survival benefit in a randomized Phase III setting, but its response rate is disappointing and it has not been compared with other currently used agents such as taxanes. Recent years have seen a better definition of prognostic and predictive factors in patients with relapsed urothelial cancer. In addition, several trials have investigated novel biological agents to target chemoresistant disease. This review provides an update on the current systemic management of advanced urothelial cancer on progression following first-line chemotherapy, and discusses emerging data from recent Phase II/III trials.