Evolving Treatment of Advanced Urothelial Cancer

Urothelial cancer of the bladder is a smoking-related cancer and the fifth most common cancer in the United States. At presentation, up to 25% of patients will have muscle-invasive disease and, despite cystectomy or bladder-sparing trimodality approaches, will develop metastatic disease. Cisplatin-based combination chemotherapy regimens remain the standard of care in first-line metastatic disease. Although response rates to these regimens are high, they are rarely durable, and median overall survival is only 12 to 15 months. Treatment options following progression on cisplatin-based regimens or for patients unfit for cisplatin due to poor performance status, impaired renal function, or comorbidities have been quite limited. However, there is now a new class of drugs known as immune checkpoint inhibitors, which target the programmed cell death 1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are showing both efficacy and tolerability. These drugs have now been approved for use in both cisplatin-treated and most recently cisplatin-unfit patients. Clinical trials are currently ongoing to determine how best to use these drugs and whether they should be used alone or in combination with other treatments. This review will discuss the current standard of care in the management of urothelial cancer and highlight recent trials of immunotherapy in this disease.