Systemic Treatment in Intermediate Stage (Barcelona Clinic Liver Cancer-B) Hepatocellular Carcinoma

Simple Summary According to the latest BCLC algorithm, the reference treatment of BCLC-B HCCs that are non-eligible for surgery or liver transplantation is trans-arterial chemoembolization. However, some BCLC-B HCCs are unsuitable for (i.e., those with diffuse, infiltrative, and extensive bilobular disease) or refractory to this treatment. To date, it has not been clarified whether systemic treatment plays a role in these cases. In this review, we provide recent data regarding this issue. Interestingly, it was shown that systemic treatment might benefit patients with BCLC-B2 and B3 hepatocellular carcinoma. Moreover, a combination of two systemic agents or even a triple combination with trans-arterial chemoembolization has been tried, giving promising results. However, further validation by RCTs is necessary before moving towards a modification of the current treatment guidelines.Abstract Hepatocellular carcinoma (HCC) represents an entity of poor prognosis, especially in cases of delayed diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, patients in BCLC-A are the most suitable for potentially curative treatments (surgery or radiofrequency ablation), whereas those in BCLC-C should be treated only with systemic treatment, as locoregional interventions are ineffective due to the tumor's extensiveness. For patients in the BCLC-B stage, trans-arterial chemoembolization (TACE) is the reference treatment, but the role of systemic treatment has been constantly increasing. As this group of patients is extremely heterogeneous, a case-by-case therapeutic strategy instead of a one-fits-all treatment is certainly required to achieve adequate results against HCC. The decision of selecting among immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), TACE, or a combination of them depends on the patient's tumor load, the severity of liver dysfunction, the general performance status, and the presence of concomitant extrahepatic diseases. The objective of this review is to critically appraise the recent data regarding the systemic treatment of BCLC-B HCCs, aiming to emphasize its potential role in the management of these difficult-to-treat patients.