Radiotherapy for Hepatocellular Carcinoma: A comprehensive update with practical recommendations.

Abstract

Management of hepatocellular carcinoma (HCC) is evolving rapidly and decisions regarding locoregional therapy are complex. External beam radiation therapy (EBRT) is a highly effective and safe intervention with an expanding role in HCC, and major guidelines (BCLC 2026, EASL, AASLD, NCCN, ASTRO) now endorse it across defined clinical settings. However, guidelines largely treat EBRT as a single modality, whereas in practice it encompasses multiple delivery techniques and nuanced technical decisions that directly influence safety and efficacy. This review provides radiation oncologists with a practical foundation for selecting patients, planning treatment, and positioning EBRT among contemporary locoregional and systemic therapies. We synthesized current consensus guidelines, prospective randomized trials, and key contemporary series evaluating EBRT for HCC, drawing on prior systematic reviews updated to include recent studies. We address liver function assessment and patient selection, practical aspects of treatment delivery (motion management, image guidance, target definition, and adaptive planning), particle therapy, comparative evidence against other locoregional therapies, combinations with systemic therapy, management of high-risk scenarios, bridging to transplant, and post-treatment surveillance. Mature prospective evidence, including randomized comparisons against chemoembolization, thermal ablation, and systemic therapy, demonstrates that EBRT achieves local control equal or superior to standard locoregional therapies with acceptable toxicity. Advances in motion management, image guidance, functional liver assessment, and adaptive planning have expanded the safe application to high-risk scenarios, such as macrovascular invasion, poor liver function, and re-irradiation, and EBRT is an effective bridging therapy. EBRT delivers excellent local control with acceptable toxicity and is now endorsed by major guidelines as an option in selected settings. As imaging, motion management, adaptive strategies, and functional liver assessment continue to evolve, EBRT can be tailored safely to patients with compromised liver reserve, macrovascular invasion, or transplant pathways. Future studies should refine patient selection and optimize combinations of EBRT with other liver-directed and systemic therapies.