Comparison of first-line immuno-oncology combinations with molecular targeted therapy in patients with advanced renal cell carcinoma undergoing hemodialysis: a real-world multicenter retrospective study

Background Patients with advanced renal cell carcinoma (RCC) undergoing hemodialysis are often excluded from clinical trials. We aimed to evaluate real-world outcomes of first-line molecular targeted therapy (MTT) and immuno-oncology (IO) combination therapies in patients with advanced RCC receiving hemodialysis. Methods We retrospectively analyzed data from 88 patients undergoing hemodialysis who received first-line systemic therapy for advanced RCC at 18 institutions in Japan between 2008 and 2023. Patients were divided into three groups by first-line regimen: MTT (n = 53), IO–IO (n = 18), or IO-tyrosine kinase inhibitor (IO–TKI, n = 17). Treatment response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were evaluated. Prognostic factors were identified using univariate and multivariate Cox regression analyses. Results The median PFS and OS were 3.9 and 18.9 months, respectively. IO–IO and IO–TKI groups achieved significantly longer PFS than the MTT group (median PFS 3.5, 5.4, and 7.5 months, respectively; p = 0.003); OS did not differ significantly among groups. Grade ≥ 3 TRAEs occurred in 30.2%, 33.3%, and 41.2% of MTT, IO–IO, and IO–TKI groups, respectively. Multivariate analysis identified poor Eastern Cooperative Oncology Group performance status, longer hemodialysis duration (≥ 10 years), and first-line regimen as independent PFS predictors. International Metastatic RCC Database Consortium risk classification and hemodialysis duration independently predicted OS. Conclusions Systemic therapy, including MTT and IO combination therapy such as IO–IO and IO–TKI, demonstrated acceptable safety profiles for patients with advanced RCC undergoing hemodialysis. IO combination therapy significantly improved PFS, supporting its utility as a first-line treatment option.