Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Immune checkpoint inhibitors (ICI) have reshaped treatment paradigms of multiple solid organ malignancies. In genitourinary malignancies (GU), ICI provide significant clinical benefit and are approved for use in localized and metastatic renal cell carcinoma and urothelial carcinoma. Investigational approaches to maximize clinical benefit and expand use of ICI across GU malignancies are actively being pursued. In addition, biomarkers predictive of clinical benefit to ICI have been identified; however, further validation and incorporation into guideline-based management remain active areas of investigation. Cancers of the genitourinary (GU) tract are common malignancies in both men and women and are a major source of morbidity and mortality. Immune checkpoint inhibitors (ICI) targeting CTLA-4, PD-1 or PD-L1 have provided clinical benefit, particularly in renal cell and urothelial carcinoma, and have been incorporated into standard of care treatment in both localized and metastatic settings. However, a large fraction of patients do not derive benefit. Identification of patient and tumor-derived factors which associate with response have led to insights into mechanisms of response and resistance to ICI. Herein, we review current approvals and clinical development of ICI in GU malignancies and discuss exploratory biomarkers which aid in personalized treatment selection.