Management of Renal Cell Carcinoma of Variant Histology

Renal cell carcinomas (RCCs) of variant histology, otherwise known as non–clear cell RCC (nccRCC), represent a broad spectrum of renal cell neoplasms with unique molecular characteristics, clinical behaviors, and treatment responses. Their management remains challenging, often requiring extrapolation from ccRCC guidelines. This review is structured by subtype and offers a guide to clinical management of nccRCC on the basis of most recent clinical trials, while also providing a focused summary of the epidemiology, molecular traits, and important diagnostic aspects of this set of neoplasms. With respect to systemic therapy for advanced cases, combination regimens with either immune checkpoint inhibitors or targeted therapies have emerged in many nccRCC subtypes with promising activity, while chemotherapy remains the standard approach for specific cases such as collecting duct carcinoma and renal medullary carcinoma. Finally, we compile some relevant trial efforts currently active for the treatment of these tumors.