The 2022 Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitor Therapy for Renal Cell Carcinoma

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD -L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not rec-ommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to pre-dict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. Patient summary: New results from three trials of immunotherapy after surgery for kid-ney cancer to reduce the risk of recurrence showed no improvement with these treat-ments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.(c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Automated summary

In the KEYNOTE-564 trial, adjuvant pembrolizumab showed significant improvement in disease-free survival (DFS) for localized clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. However, other immunotherapies, such as adjuvant atezolizumab, adjuvant nivolumab plus ipilimumab, and perioperative nivolumab did not meet the primary DFS endpoints. A meta-analysis is not recommended due to heterogeneity. Pembrolizumab remains the only recommended immune checkpoint inhibitor for this indication, but overall survival data are still immature and predictive biomarkers are lacking. Treatment decisions should be made cautiously and with patient involvement.