Integrating systemic therapy in the earlier stages of liver cancer

The treatment of advanced primary liver cancer has seen major improvement in recent years. In hepatocellular carcinoma (HCC), immunotherapy has improved both survival and quality of life. In biliary tract cancers (BTC), immunotherapy has shown modest benefits, while molecular targeted therapies have had a major impact in selected populations defined by molecular alterations. These advances are now being tested at earlier disease stages. In this review, we first discuss the challenges in designing trials that combine local and systemic treatment at earlier stages, and the different endpoints that might be used. We then present the available data on the combination of intra-arterial and systemic treatments in HCC. We continue with a discussion of the available data on adjuvant and neoadjuvant systemic treatment in HCC. Finally, we review recent developments in the adjuvant and neoadjuvant settings for BTC. While promising data exist across these settings, uncertainties remain regarding whether these strategies will become standard of care in the coming years.