Systemic Treatment for Metastatic Bladder Cancer

Abstract

Metastatic bladder cancer is generally incurable, with a median survival of 14 to 15 months under a modern chemotherapy regimen. Cisplatin-based chemotherapy, including the combination regimens methotrexate-vinblastine-doxorubicin-cisplatin and gemcitabine-cisplatin, are the standard first-line therapy. Despite response rates of 40% to 60% achieved, most patients’ cancers progress after about 8 months. Second-line single agents have only marginal efficacy after cisplatin-based treatment failure, with objective response rates of 5% to 20% and a median progression-free survival of only 3 to 4 months. Moreover, there is little evidence that second-line systemic treatment can substantially improve overall survival or quality of life. Agents targeting growth, survival, and proliferation pathways have been added to cytotoxic therapy with limited added benefits to date. Drugs that modulate the host immune response to cancer-associated antigens, including immunologic checkpoint blockade by antibodies against programmed cell death protein-1 or its ligands, appear promising, and multiple new therapeutic approaches are being pursued. In addition, the receptor tyrosine kinase/Ras pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin pathway represent potential therapeutic targets for advanced disease, and novel agents are in development. (Korean J Med 2015,89:515-521)