Evolving treatment paradigm in metastatic non clear cell renal cell carcinoma

The treatment landscape for renal cell cancer (RCC) has evolved tremendously over the last two decades. Treatment algorithms have shifted from the highly toxic drugs with marginal benefit to better tolerated and more effective targeted therapy drugs. The latter include tyrosine kinase inhibitors, vascular endothelial growth factor inhibitors, MET inhibitors and, more recently, immunotherapy drugs alone and in various combinations. The majority of treatment algorithms for non-clear cell carcinoma have been based on extrapolating results from clear cell RCC trials and retrospective reviews. However, now that we understand that non-clear cell RCC is morphologically and clinically distinct from its clear cell counterpart, several collaborative clinical trials are underway for non-clear cell RCC. This review will delve into the historical aspects of treating non-clear cell RCC and the evolution of treatment paradigms over the last few decades with a focus on immunotherapy based trials.