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 recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict 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 kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. 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.

Department of Cancer Medicine Gustave Roussy Université Paris Saclay Villejuif France

Department of Surgical and Perioperative Sciences Urology and Andrology Umeå University Umeå Sweden

Department of Translational Medicine Division of Urological Cancers Lund University Malmö Sweden

Department of Urology Cabueñes University Hospital Gijón Spain

Department of Urology Chaim Sheba Medical Center Tel Hashomer Ramat Gan Israel

Department of Urology Charité Universitätsmedizin Berlin Berlin Germany

Department of Urology Coimbra University Hospital Coimbra Portugal

Department of Urology Homerton University Hospital London UK

Department of Urology San Raffaele Scientific Institute Milan Italy; Division of Experimental Oncology Unit of Urology Urological Research Institute IRCCS San Raffaele Hospital Milan Italy

Department of Urology Sunderby Sjukhus Umeå University Luleå Sweden

Department of Urology University Hospital Pilsen and Faculty of Medicine in Pilsen Charles University Czech Republic

Department of Urology University Hospital Tübingen Tübingen Germany; German Cancer Consortium and German Cancer Research Center Heidelberg Germany

Department of Urology University of Eastern Piedmont Maggiore della Carità Hospital Novara Italy

International Kidney Cancer Coalition Duivendrecht The Netherlands

The Royal Free London NHS Foundation Trust London UK; UCL Division of Surgery and Interventional Science University College London London UK; Department of Urology The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

The Royal Free NHS Trust and Barts Cancer Institute Queen Mary University of London London UK

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Renal cell carcinoma with intracardiac tumor thrombus extension: Radical surgery yields 2 years of postoperative survival in a single-center study over a period of 30 years