Options in metastatic urothelial cancer after first-line therapy

Abstract

The treatment of patients with metastatic urothelial carcinoma is evolving with recent advances holding promise for improved outcomes. Historically, patients with metastatic urothelial carcinoma had a poor prognosis with no standard treatment options in the second-line setting. Currently, with an increased understanding of the heterogeneity of clinical bladder cancer subtypes and molecular diversity of the disease, there is optimism that outcomes will start to improve. The present review will evaluate historical second-line treatment options and focus on emerging therapies in this setting. Single-agent cytotoxic chemotherapy agents continue to be evaluated in patients with metastatic urothelial carcinoma with variable results. Targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, have also been extensively evaluated in this disease. Early phase data have as yet failed to demonstrate improvements in survival; however evaluations of targeted agents in enriched patient populations and in combination with chemotherapeutic agents are ongoing. Novel immunotherapeutic approaches have shown encouraging results and are currently being evaluated extensively. The optimal treatment for patients with metastatic urothelial carcinoma in the second-line setting is unknown. Recent advances in the field gives rise to optimism as the focus shifts to individualization of therapy based on clinical and molecular characteristics of the patient and the disease.