The State of the Art in Combination Locoregional and Systemic Treatment Strategies for Hepatocellular Carcinoma: Recent Advancements and Future Horizons

Hepatocellular carcinoma remains one of the most common and lethal cancers worldwide, and many patients are diagnosed at stages where curative therapy is not possible. Recent progress in systemic therapies and refinements in locoregional treatment have shifted how clinicians approach this disease. As evidence has accumulated from trials such as KEYNOTE-937, IMbrave050, and CheckMate 9DX, it has become clear that pairing immunotherapy with ablation or transarterial interventions can deepen and extend treatment responses compared with using either approach alone. This review summarizes the current landscape of these combination strategies, explains the biological and clinical principles that support their use, and highlights ongoing trials that aim to clarify optimal sequencing and patient selection. It also considers future directions for integrating locoregional and systemic therapies to expand curative opportunities and improve long-term outcomes for a broader range of patients.