Therapy of Intermediate-Stage Hepatocellular Carcinoma: Current Evidence and Clinical Practice

Abstract

Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.

Keywords: Barcelona Clinic Liver Cancer; ablation; hepatocellular carcinoma; radioembolization; transarterial chemoembolization.

Fig. 1

Imaging of conventional transarterial chemoembolization treatment with intraprocedural cone-beam computed tomography (CBCT) guidance. Pretreatment magnetic resonance imaging (MRI) reveals an arterially hypervascular tumor in segment 8 of the liver (white arrow) ( a ). Angiographyrevealed tumor blush in the expected location (white arrow) ( b ). Intra procedural CBCT was performed, revealing washout on the delayed imaging phase (white arrow) ( c ). The feeding vessel to the tumor was selected and embolized using doxorubicin emulsified with Lipiodol followed by polyvinyl alcohol particles. Preferential Lipiodol uptake by the tumor can be noted on both angiography (white arrow) ( d ) and CBCT ( e ). Follow-up MRI 1 month after the procedure demonstrates complete response with absence of any residual contrast enhancement (white arrow) ( f ).