Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma

Metastatic urothelial cancer is an aggressive disease associated with a poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. After failure of platinum-based therapy and in cisplatin-ineligible patients, therapeutic options are limited. Malignant cells evolve mechanisms to evade immune recognition, including the expression of cell-surface molecules, named immune checkpoints, on tumor and tumor-specific lymphocytes. Immunotherapy, by targeting these checkpoints, represents a new tool to improve the patient outcome in advanced urothelial carcinoma (UC). Recently, the US FDA approved, in a short time, several immune checkpoint inhibitors in metastatic UC, both after failure of platinum-based therapy and in first-line setting in cisplatin-ineligible patients. This article aims to review the place of immunotherapy in advanced UC. Lay summary: Urothelial carcinoma is an aggressive disease and therapeutic options are limited in patients with advanced stage who are refractory to chemotherapy. Immunotherapy represents a milestone for these patients; different immune checkpoint inhibitors have shown significant activity in advanced urothelial carcinoma and are currently available both in the second-line metastatic setting (after failure of platinum-based therapy) and in the first-line setting in cisplatin-ineligible patients. Furthermore, these agents are better tolerated than chemotherapy. PD-L1 expression is not an ideal biomarker and further research is evaluating innovative methods to facilitate selection of patients who are most likely to benefit from these agents.