Abstract
Global incidence of hepatocellular carcinoma (HCC) is rising along with its mortality burden, and more than half of the patients require systemic therapy for advanced disease. There is an ongoing epidemiologic shift in risk factors for HCC from hepatotropic virus-related liver disease to alcohol and metabolic dysfunction-associated steatotic liver disease. Although a diagnosis of HCC can be made with noninvasive radiologic criteria, tissue biopsy is gaining a role, at least within the realm of clinical trials. Despite advances in targeted therapies, the role of molecular testing in HCC remains unclear. Liver function continues to play a vital role in the management of HCC across all stages. With the approval of immune checkpoint inhibitors and tyrosine kinase inhibitors targeting tumor angiogenesis, the treatment landscape of advanced HCC has evolved considerably in the past decade, leading to improvements in patient outcomes. However, optimal sequencing of these agents is not well defined. There are several ongoing trials evaluating systemic therapies with novel mechanisms of action including adoptive cell therapy. This review aims to provide practicing oncologists with a comprehensive overview of recent developments in systemic therapy for the management of advanced HCC.