Extrahepatic Oncological Applications of Yttrium-90 Radioembolization: A Translational Review

Abstract Yttrium-90 (Y90) radioembolization is an established locoregional therapy in selected hepatic malignancies, and its underlying principles—selective arterial delivery, microvascular deposition, and high local radiation dose with relative sparing of surrounding tissue—have prompted investigation beyond the liver. This review examines extrahepatic Y90 across three disease settings with the most developed translational pathways: glioblastoma (GBM), prostate cancer, and renal cell carcinoma (RCC). For each, we summarize the biologic and preclinical rationale, available human experience, and ongoing clinical investigation. Among these disease sites, the most mature published human data come from GBM and RCC, where early-phase studies have demonstrated technical feasibility, organ-specific deliverability, and initial safety signals, while key questions remain regarding dose selection, durability of response, patient selection, and integration with standard therapies. In prostate cancer, the rationale for intra-arterial radiotherapy is biologically attractive, but clinical development remains earlier, with human data still emerging. Across disease types, extrahepatic application introduces organ-specific challenges in arterial mapping, nontarget protection, dosimetry, response assessment, and multidisciplinary integration that differ from hepatic practice. Extrahepatic Y90 remains an investigational extension of radioembolization, with its role contingent on translating early feasibility and dosimetric promise into reproducible clinical benefit through prospective study.