The KEYNOTE-564 randomised controlled trial showed a disease-free survival benefit of adjuvant pembrolizumab (aPZB) in comparison to placebo for patients with clear cell renal cell carcinoma (ccRCC) at high risk of recurrence.
Despite its recommendation by the European Association of Urology guidelines, the ultimate value of aPZB has recently been questioned. Arguably, patients who might benefit the most from aPZB are those whose probability of RCC recurrence outweighs their probability of dying from other causes over a reasonable timeframe after surgery. To assess the potential impact of this hypothesis on "eligibility" for aPZB, we queried our prospectively collected multi-institutional database for consecutive patients undergoing surgery for nonmetastatic renal masses (cT1-4 N0-1 M0) between 2015 and 2021 to identify ccRCC cases meeting the KEYNOTE-564 criteria. We stratified the patients using the risk-adapted model proposed by Stewart-Merrill et al (whereby stopping follow-up is warranted when the estimated risk of other-cause mortality [OCM] outweighs the estimated risk of RCC recurrence). Then we explored the proportion of patients whose follow-up could theoretically be stopped at 2, 5, 10, or 20 yr, for whom "eligibility" for aPZB might be more controversial. Overall, 1745 patients with ccRCC were included, of whom 419 (24%) met the KEYNOTE-564 criteria. The proportion of patients "not eligible" for aPZB because of higher probability of OCM than of RCC recurrence would have been 81%, 66%, 43%, and 29% at "recommended" follow-up of ≤2.0, ≤5, ≤10, and ≤20 yr, respectively. To the best of our knowledge, this is the first study providing insights to support shared decision-making regarding eligibility for aPZB for patients with nonmetastatic ccRCC with a focus on patient-related factors beyond tumour-driven prognostic scores. PATIENT SUMMARY: An immunotherapy drug call pembrolizumab given after surgery for nonmetastatic kidney cancer may benefit some patients who have a high risk of disease recurrence, but it can have immune-related side effects. We found that comparing the risk of death from other causes and the risk of cancer recurrence could help in reducing overtreatment of patients who might not benefit from this drug.
European urology oncology. 2023 Nov 07 [Epub ahead of print]
Riccardo Campi, Alessio Pecoraro, Eduard Roussel, Daniele Amparore, Andrea Mari, Francesco Montorsi, Francesco Porpiglia, Maarten Albersen, Umberto Capitanio, Andrea Minervini, Sergio Serni, Riccardo Bertolo
Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Young Academic Urologists Renal Cancer Working Group, Arnhem, The Netherlands. Electronic address: ., Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Orbassano, Italy., Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Unit of Urological Oncologic Minimally Invasive Robotic Surgery and Andrology, Careggi Hospital, University of Florence, Florence, Italy., Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy., Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Department of Urology, San Carlo Di Nancy Hospital, Rome, Italy.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37945489