The evolving role of selective internal radiation therapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains a major global oncological burden, accounting for over 900,000 new diagnoses and more than 800,000 deaths each year. Most patients present with intermediate or advanced disease on a background of cirrhosis, restricting curative strategies such as surgical resection or liver transplantation to only 20-30% of cases. Selective internal radiation therapy (SIRT), also known as yttrium-90 transarterial radioembolization, exploits the preferential arterial blood supply of HCC to deliver high-dose beta radiation selectively to tumor tissue while sparing non-tumorous liver parenchyma, thereby inducing targeted DNA damage and apoptosis with minimal ischemic injury. Evidence updated to November 2025 from randomized controlled trials, large registries, and recent meta-analyses demonstrates that SIRT provides overall survival comparable to transarterial chemoembolization (TACE), while consistently improving progression-free survival, time-to-progression, objective response rates, and patient-reported quality of life. These benefits are particularly evident in patients with large tumors, bilobar involvement, or TACE-refractory disease. Importantly, SIRT enables effective downstaging to liver transplantation eligibility according to Milan or University of California San Francisco criteria in approximately 40-66% of cases, with pathological complete response rates approaching 90% when applied as radiation segmentectomy. SIRT shows a favorable safety profile, with grade ≥3 adverse events in only 11-18% of patients, minimal post-embolization syndrome, and radioembolization-induced liver disease in fewer than 5%, preserving liver function and quality of life. Current European Association for the Study of the Liver (EASL 2024) and American Association for the Study of Liver Diseases (AASLD 2023) guidelines recognize SIRT as an alternative locoregional therapy in selected intermediate-stage and carefully chosen advanced-stage HCC patients. Emerging innovations continue to refine outcomes.