Adjuvant and neoadjuvant therapies in HCC: Time to go perioperative?

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with high recurrence rates despite curative-intent therapies. Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced disease and are now being explored in earlier stages. However, adjuvant approaches have shown limited and inconsistent benefit across phase III trials. In contrast, neoadjuvant strategies have demonstrated promising activity, likely due to enhanced immune priming in the presence of an intact tumor, leading to improved pathological responses and potential tumor downstaging. Emerging evidence suggests that perioperative approaches combining neoadjuvant and adjuvant immunotherapy may provide a more comprehensive strategy by targeting both macroscopic and microscopic disease. Early phase III data indicate improved oncological outcomes and possible conversion to resectability in selected patients. Nonetheless, challenges remain, including patient selection, optimal sequencing, toxicity, and lack of predictive biomarkers. This review summarizes current evidence and future perspectives on adjuvant, neoadjuvant and perioperative systemic therapies in HCC.