Current status of adjuvant immunotherapy and relapse management in renal cell carcinoma: Insights from a European delphi study

Introduction: Adjuvant immunotherapy has remarkably advanced the management of localized renal cell carcinoma (RCC) in patients at high risk of post-surgery recurrence. This Delphi study aimed to establish expert consensus on its use and subsequent management of relapse. Methods: Fifteen RCC experts participated in a two-round Delphi process between July and November 2024. The study included 43 core survey items, divided into 67 components for comprehensive evaluation. Results: Consensus, defined as ≥ 75 % agreement, was achieved for 39 of 67 items (58.2 %). Experts agreed on using the Leibovich score for selecting patients for adjuvant pembrolizumab (79 %), initiating therapy within 90 days post-surgery (86 %), and not restricting treatment to programmed death ligand-1 (PD-L1)-positive tumors (100 %). Plasma kidney injury molecule-1 (KIM-1) was considered by the experts as a potential useful recurrence risk biomarker (93 %). Immune checkpoint inhibitor (ICI)-refractory disease was defined as relapse within 6 months post-adjuvant therapy (80 %). Focal therapies for oligometastatic recurrence (80 %), and targeted therapies or clinical trial enrollment for ICI-refractory patients (87 %) were supported. Belzutifan was recommended for fourth-line or later use after ICI therapy and multiple tyrosine kinase inhibitors (93 %). By contrast, no consensus was reached on ICI salvage therapy in specific subgroups, including patients with clear-cell RCC (60 %), without bone/brain metastases (60 %), good performance status (60 %), low tumor burden (47 %), or papillary RCC (36 %). Conclusions: This Delphi study provides insights into the evolving role of adjuvant immunotherapy in localized RCC and relapse management. A multidisciplinary approach and periodic review are essential to optimizing treatment strategies.