Perioperative immunotherapy for hepatocellular carcinoma: adjuvant, neoadjuvant, and biomarker-guided strategies

Hepatocellular carcinoma (HCC) remains difficult to cure after resection or ablation, with high recurrence rates. Perioperative immunotherapy has rapidly evolved, but recent late-phase readouts highlight that benefit is not universal. In IMbrave050, adjuvant atezolizumab plus bevacizumab initially improved recurrence-free survival (RFS), yet longer follow-up suggests attenuation of effect, influencing guideline recommendations. By contrast, adjuvant single-agent checkpoint inhibitor programs have not shown consistent benefit, although selected high-risk subgroups [e.g., microvascular invasion (MVI)] may derive benefit from adjuvant PD-1 blockade in phase II data. Perioperative combinations are emerging, including camrelizumab plus rivoceranib with improved event-free survival, and locoregional-immunotherapy strategies such as transarterial chemoembolization combined with immunotherapy-antiangiogenic regimens. Biomarker-driven selection, circulating tumor DNA for minimal residual disease, resistance-associated alterations (e.g., CTNNB1), and etiology-linked immune phenotypes, will be central to optimizing patient selection and treatment sequencing.