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There has been significant progress made in the treatment of clear-cell renal cell carcinoma (RCC), with several targeted agents now approved. However, the vast majority of patients develop progressive disease within a year. Despite the clinical efficacy of targeted agents, significant toxicity hampers patient benefit, and <30% of patients with metastatic RCC survive >five years. Furthermore, insight into the biology of non-clear cell RCC subtypes has lagged behind clear-cell RCC, with few relevant targets identified. Currently, there is no established effective therapy for this diverse group of non-clear cell RCC subtypes. Therapeutic strategies using immune checkpoint antibodies are revolutionizing the treatment of many cancers including RCC, but at best 50% of patients with metastatic RCC respond to the combination of anti-PD-1 and anti-CTLA-4 antibodies. The long-term follow-up of patients with metastatic RCC treated with these novel immune approaches will be awaited to assess their curative potential.
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