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Kidney cancer treatment has been first revolutionized by the advent of targeted therapies (TKIs and mTOR inhibitors) and then by the approval of immunotherapy and immunocombinations. Whereas immunocombinations represent the most used first-line therapy in intermediate/poor risk patients with clear-cell tumors, cabozantinib and nivolumab are both effective compounds at progression, and till today it is not totally clear what to prefer. No standard treatments are approved in post-second-line setting and in non-clear carcinoma. The aim of this review is to summarize the main evidence supporting the use of targeted therapies and immunotherapy, in every setting of clear-cell and non-clear cell renal cell carcinoma, while also providing an insight into promising ongoing and upcoming trials. We speculate on what could help physicians in guiding the therapeutic decision-making process in advanced kidney cancer. International mRCC Database Consortium criteria are still recommended for the choice of primary treatments, despite presenting several limitations in the current immunotherapy-era. Multiple predictors of response to immunotherapy or targeted therapies are emerging but validated biomarkers are awaited. Furthermore, we discuss therapeutic sequences in kidney cancer, guessing how physicians may prefer immunotherapy or TKI as later-line strategies on the basis of previous treatments.

Guiding treatment selection with immunotherapy compared to targeted therapy agents in patients with metastatic kidney cancer