Recent advances in therapeutic and surgical approaches in locally advanced HCC: downstaging and neoadjuvant therapy

Hepatocellular carcinoma is a leading cause of cancer-related mortality, with surgical treatments such as liver resection and liver transplantation offering curative potential but a high risk of recurrence. Recent advances in immunotherapy have shown promise in the treatment of advanced-stage hepatocellular carcinoma, and their potential role in earlier stages, particularly in resectable and locally advanced disease, is gaining increased attention. Neoadjuvant immunotherapy, including immune checkpoint inhibitors used alone or in combination, has demonstrated encouraging response rates and favorable pathological outcomes in clinical trials. These therapies may downstage tumors, enhance surgical resectability, and improve survival outcomes. However, challenges persist, particularly in standardizing criteria for treatment response and managing immune-related adverse events. Evidence also supports the combination of immunotherapy with locoregional therapies, such as transarterial chemoembolization and radiation, which may further improve therapeutic efficacy by inducing tumor regression and enhancing immune activation. Ongoing clinical trials and the exploration of emerging biomarkers, such as circulating tumor DNA, are crucial for optimizing patient selection and predicting treatment success. While neoadjuvant immunotherapy holds potential for improving outcomes in hepatocellular carcinoma, further research is needed to determine its precise role and long-term benefits in both resectable and unresectable disease.