Systemic Therapy for Unresectable Hepatocellular Carcinoma: Present Landscape and Future Challenges

The World Health Organization’s global health estimates in 2022 showed that primary liver cancer ranks as the sixth most common cancer globally, impacting over 866,000 patients worldwide, and is the third leading cause of cancer death globally, with a higher prevalence in Asia. Hepatocellular carcinoma (HCC) contributes 85–90% of primary liver cancer. Despite vaccinations and screening programs, HCC patients far too often present with advanced, unresectable disease. The underlying liver disease compromising liver function often perplexes treatment. Common etiologies include chronic viral hepatitis (types B and C), excessive alcohol consumption, and exposure to aflatoxin, with significant geographic variation. The therapeutic landscape for unresectable HCC (uHCC) is advancing with the advent of novel agents. Bona fide validation on the management of uHCC remains a challenge, especially across geographic areas. There is, at present, no consensus guideline on the optimal treatment sequence. In this chapter, we discuss the present landscape of treatment and future challenges.