**7. Adjuvant and neoadjuvant immunotherapy**

With the promising outcome of immunotherapy in mRCC, it is reasonable to explore whether immunotherapy works in the non-metastatic adjuvant setting. Noteworthy, spontaneous antitumor immune infiltration was shown to be higher in primary tumors with respect to matched metastases [92], suggesting that the administration of immunotherapy in the early setting might be more effective than in the advanced setting. However, trials of adjuvant therapy involving tumor cell vaccination, IFN-α, or HD IL-2 have not shown survival benefits [93]. Trials studying the role of checkpoint inhibition (anti PD-1/PD-L1 agents) are proceeding, and the results are eagerly awaited. Studies are also under way to determine the feasibility of ICIs as neoadjuvant (nivolumab, NCT02575222, NCT02595918; durvalumab with or without tremelimumab, NCT02762006) or adjuvant therapy (nivolumab; NCT02595944, NCT02388906, NCT02743494, NCT02632409; pembrolizumab, NCT02362594, NCT02504372; atezolizumab, NCT02450331, NCT02927301, NCT02912559, NCT02486718). We believe that a big movement in RCC management will occur if we can find a way to increase survival rates in the adjuvant or neoadjuvant setting of surgically managed patients.
