Pattern of disease recurrence and outcomes after progression of high-risk renal cell carcinoma (RCC) patients treated with adjuvant immunotherapy

Background: Radical or partial nephrectomy followed by adjuvant pembrolizumab is the standard of care for high-risk localized renal cell carcinoma (RCC), yet around 40% of patients relapse within 5 years. We investigated patterns of disease recurrence and the clinical management of RCC patients treated with adjuvant immunotherapy. Materials and methods: We collected patients with high-risk RCC who received adjuvant immunotherapy after radical surgery in our Institution. The primary endpoint was the rate and pattern of disease recurrence. Secondary endpoints were disease-free survival (DFS), overall survival (OS), post-progression survival (OS2) and treatments at recurrence. Results: From March 2018 to September 2025, 70 patients were included, most received adjuvant pembrolizumab (71%), followed by nivolumab + ipilimumab (16%), and nivolumab monotherapy (13%). 15 patients (21%) experienced recurrence, including 7 (10%) who relapsed on adjuvant treatment. Oligometastatic disease was observed in 10 cases (67%), mainly involving lung (60%), lymph nodes (33%) and renal bed (13%). At recurrence, 9 patients (60%) started first-line therapy, while 5 patients (33%) received loco-regional treatments. After a median follow-up of 30.2 months, 30-month DFS and OS rates were 74% and 94%, respectively, in the overall population. Among patients who progressed, the 24-month OS2 rate was 100% after local therapy alone and 86% with systemic therapy. Conclusions: High-risk RCC patients treated with adjuvant immunotherapy remain at considerable risk of relapse, frequently with oligometastatic disease. Excellent post-progression outcomes after loco-regional treatment support a multidisciplinary, metastasis-directed approach to recurrence after adjuvant immunotherapy.