(UroToday.com) The 2023 EAU annual meeting included a session on locally advanced kidney cancer, featuring a presentation by Dr. Riccardo Campi discussing refining the indication for adjuvant pembrolizumab in patients with clear cell renal cell carcinoma (RCC) at high risk of recurrence using a risk-adapted approach. The EAU Guidelines on RCC currently recommend adjuvant pembrolizumab in patients with clear cell RCC at higher risk of recurrence after surgery based on the results of the KEYNOTE-564 trial.1 The aim of the current study was to evaluate the proportion and characteristics of patients with localized clear cell RCC who would have been eligible for adjuvant therapy according to the KEYNOTE-564 inclusion criteria, as well as to provide insights on the potential cost-effectiveness of adjuvant pembrolizumab using a risk-adapted approach.
After Ethical Committee approval, Dr. Campi and colleagues queried their prospectively maintained databases to identify patients with cT1-T4N0-N1M0 clear cell RCC who underwent partial or radical nephrectomy from January 2015 to December 2021 at four high-volume referral European Centers. Patients were classified as eligible vs non-eligible for adjuvant pembrolizumab. The eligible patients were stratified according to the follow-up timeframes recommended by the risk-adapted strategy by Stewart-Merrill et al.2 Then, they explored how the proportion of eligible patients would change if specific cut-offs of “minimum” follow-up after surgery were considered “cost-effective” (> 2, > 5, > 10 or > 20 years).
There were 82.4% (2,725/3,309) of tumors that were malignant, of which 54.1% (1,475/2,725) were clear cell RCC, of which 419 (28.4%) were classified as eligible for adjuvant pembrolizumab (intermediate-high risk: 83%; high risk: 17%):
Patients who were not eligible for adjuvant pembrolizumab were younger (median age 64 vs 68 years, p<0.01), had a higher comorbidity burden (CCI≥ 2 in 50.8% vs 43.0%, p < 0.01), and less often underwent radical nephrectomy (8.1% vs 60.4%, p<0.01). Applying the Stewart-Merrill’s risk-based approach for recommended follow-up based on balancing risk of RCC-related mortality versus risk of other cause mortality, the proportion of eligible patients for pembrolizumab dropped from 100% (considering no limits for follow-up periods) to:
- 87.7% (considering only patients whose recommended follow-up was > 2 years)
- 73.1% (considering only patients whose recommended follow-up was > 5 years)
- 42.8% (considering only patients whose recommended follow-up was > 10 years)
- 28.6% (considering only patients whose recommended follow-up was > 20 years)
Patients with pN+ disease and those who are younger (<50 y or 50-59 years) and less comorbid (CCI 0-1) represented the groups who might benefit the most in this perspective:
Dr. Campi concluded his presentation discussing refining the indication for adjuvant pembrolizumab in patients with clear cell renal cell carcinoma at high risk of recurrence using a risk-adapted approach with the following take-home messages:
- Almost one out of three contemporary patients with clear cell RCC could be eligible for adjuvant pembrolizumab
- Applying a risk-adapted approach (based on pTNM stage, age and comorbidities), and selecting specific cut-offs of recommended follow-up time after surgery to consider adjuvant pembrolizumab is “cost-effective”, and the proportion of eligible patients might be reduced
- Further research is needed to identify the best candidates for adjuvant pembrolizumab, balancing the potential oncologic benefits, risks of adverse events, and individual patient’s prognosis
Presented by: Riccardo Campi, Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Dept. of Experimental and Clinical Medicine, Florence, Italy
Co-Authors: Pecoraro A.1, Roussel E.2, Amparore D.3, Mari A.4, Grosso A.A.4, Checcucci E.3, Montorsi F.5, Larcher A.6, Van Poppel H.2, Porpiglia F.3, Capitanio U.6, Minervini A.4, Albersen M.2, Serni S.1
Affiliations: 1Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Dept. of Experimental and Clinical Medicine, Florence, Italy, 2University Hospitals Leuven, Dept. of Urology, Leuven, Belgium, 3San Luigi Hospital, University of Turin, Division of Urology, Dept. of Oncology, School of Medicine, Turin, Italy, 4Unit of Urological Oncologic Minimally Invasive Robotic Surgery and Andrology, University of Florence, Dept. of Experimental and Clinical Medicine, Florence, Italy, 5IRCCS San Raffaele Scientific Institute, Dept. of Experimental Oncology, Dept. of Urology, Milan, Italy, 6IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology/Unit of Urology, Milan, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) 38th annual congress held in Milan, Italy between March 10-13, 2023
- Choueiri TK, Tomczak P, Park SH, et al. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694.
- Stewart-Merrill SB, Thompson RH, Boorjian SA, et al. Oncologic Surveillance after Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach. J Clin Oncol. 2015 Dec 10;33(35):4151-4157.