The current landscape of therapies for hepatocellular carcinoma.

Globally, primary liver cancer is the third leading cause of cancer-related deaths, with approximately 830 000 deaths worldwide in 2020, accounting for 8.3% of total deaths from all cancer types (1). This disease disproportionately affects those in countries with low or medium Human Development Index scores in Eastern Asia, South-Eastern Asia, and Northern and Western Africa (2). Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often develops in the background of chronic liver disease, caused by hepatitis B or C virus, non-alcoholic steatohepatitis (NASH), or other diseases that cause cirrhosis. Prognosis can vary dramatically based on number, size, and location of tumors. Hepatic synthetic dysfunction and performance status (PS) also impact survival. The Barcelona Clinic Liver Cancer (BCLC) staging system best accounts for these variations, providing a reliable prognostic stratification. Therapeutic considerations of this complex disease necessitate a multidisciplinary approach and can range from curative-intent surgical resection, liver transplantation or image-guided ablation to more complex liver-directed therapies like transarterial chemoembolization (TACE) and systemic therapy. Recent advances in the understanding of the tumor biology and microenvironment have brought new advances and approvals for systemic therapeutic agents, often utilizing immunotherapy or VEGF-targeted agents to modulate the immune response. This review will discuss the current landscape in the treatments available for early, intermediate, and advanced stage HCC.