Pattern of disease recurrence and outcomes of localized high-risk renal cell carcinoma (RCC) patients treated with adjuvant (adj) immunotherapy: A single center experience.

Abstract

510 Background: Standard treatment for high-risk localized RCC is radical or partial nephrectomy followed by adjuvant pembrolizumab. However, about 40% of patients progress within 5 years despite adjuvant immunotherapy. We sought to investigate the pattern of disease recurrence and the clinical management of RCC patients treated with adjuvant immunotherapy. 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 patients’ outcomes in terms of disease-free survival (DFS) and overall survival (OS). Results: From March 2018 to September 2025, 70 patients were included in the analysis. 15 patients (21%) had disease recurrence, 7 of which (10%) during adjuvant treatment; in 10 cases (67%) the absolute number of metastases was ≤3, with a number of diverse metastatic sites ranging from 1 (n = 9, 60%) to maximum 3 (n = 1, 7%). The most frequent sites of metastasis were lung (60%), lymph node (33%) and renal bed (13%). In case of disease recurrence, 9 patients (60%) started systemic first-line therapy (60%), while 5 patients (33%) received loco-regional treatment (1 patient radiotherapy and 4 patients metastasectomy, all alive without subsequent progression disease). After a median follow-up of 30.2 months (26.8-33.6 months), the 30-months DFS rate was 74% in the overall population and 72% for patients treated with adjuvant pembrolizumab. The 30-months OS rate was 94% in the overall population and 92% after adjuvant pembrolizumab. For patients with a DFS event, after a median follow-up of 24.5 months, the 30-months OS rate was 100% for patients who received a local treatment and 88% for patients who received systemic treatment (p = 0.56). Conclusions: Patients with RCC treated with adjuvant immunotherapy are confirmed to be at high risk of recurrence (26% at 30 months), reinforcing the need of more efforts to further improve therapeutic strategies in the adjuvant setting. Patients treated with a loco-regional approach after recurrence showed excellent survival outcomes without requiring systemic therapy. These findings support the consideration of loco-regional approach as a valid option for the management of these patients.