Response to systemic therapy in locally advanced and metastatic renal cell carcinoma: can it be predicted?

Introduction : Renal cell carcinoma is no longer considered a monolithic disease, but a group of different entities exhibiting unique molecular alterations requiring a tailored systemic approach. One of the remaining challenges is the identification of the best candidate for a particular therapeutic regimen. Areas covered : Current literature regarding the recent advances and treatment options in systemic therapy for metastatic RCC, and issues pertaining to the available biomarkers tested to date for a correct treatment stratification. Expert opinion : Underlying biology of RCC will still drive the development of new treatment agents/combinations that will be tested in earlier stages of the disease, and probably prove to have a role in the neoadjuvant/adjuvant settings. The correct characterization of the tumor microenvironment through transcriptomic analysis should help to overcome the issues related to tumor heterogeneity. Preclinical ex-vivo models will enlarge our current knowledge regarding the potential immune-escape mechanisms exhibited by RCC, and facilitate a better monitoring of the response to therapy. New tracers, image modalities, and tests aimed at detecting and analyzing tumor-circulating cells will improve our clinical performance through a better identification of the metastatic site locations and their variable histologic patterns, and ultimately their behavior in response to treatment.