Debates and progress in the management of intermediate-stage (BCLC stage B) hepatocellular carcinoma

Abstract

With the global incidence of hepatocellular carcinoma (HCC) on the rise, precise staging has become critical for guiding treatment decisions and improving long-term outcomes. The Barcelona Clinic Liver Cancer (BCLC) staging system, widely used for HCC classification, incorporates factors such as Child–Pugh A or B liver function, tumor size and number, absence of cancer-related symptoms, and lack of vascular invasion or extrahepatic metastasis. For intermediate-stage HCC, transarterial chemoembolization (TACE) remains the globally recommended standard. However, the substantial heterogeneity in tumor burden and liver function among patients means that not all individuals benefit equally from TACE. As a result, a uniform treatment approach is insufficient. Preserving liver function is now recognized as equally important as achieving high objective response rates, with the ultimate goal of prolonging overall survival. In response, researchers have proposed advanced stratification methods for stage B HCC to optimize therapeutic outcomes. While these stratification criteria remain under debate, there is a growing shift from TACE-centric strategies toward personalized targeted therapies for specific subpopulations. This review explores advanced stratification concepts, evaluates corresponding treatment strategies, analyzes ongoing clinical trials, and assesses their potential to transform the management of intermediate-stage HCC—while also outlining future directions for its treatment.