A Proposal for a Simple Subclassification of Advanced Hepatocellular Carcinoma in Systemic Treatment

Area of Science:

• Hepatobiliary oncology
• Cancer metastasis research
• Systemic cancer therapy

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern.
• Prognostic factors for unresectable HCC receiving systemic therapy require further clarification.
• Vascular invasion and extrahepatic metastasis are known indicators of poor prognosis in HCC.

Purpose of the Study:

• To evaluate the impact of vascular invasion and extrahepatic metastasis on systemic treatment outcomes in unresectable HCC.
• To identify distinct prognostic subgroups within advanced HCC based on these metastatic features.
• To explore the potential for a novel staging category for HCC.

Main Methods:

• Retrospective analysis of 362 patients with unresectable HCC receiving first-line systemic therapy.
• Prognostic evaluation based on the presence of vascular invasion and extrahepatic metastasis at treatment initiation.
• Subgroup analysis of advanced HCC patients (vascular invasion and/or extrahepatic metastasis) into 'm' (metastasis only), 'v' (vascular invasion only), and 'vm' (both) groups.

Main Results:

• Patients with vascular invasion or extrahepatic metastasis (advanced group) had significantly worse outcomes (median survival 434 days) than those without (intermediate group, 658 days).
• Within the advanced group, patients with only extrahepatic metastasis ('m' group) showed significantly better outcomes (median survival 649 days) compared to those with only vascular invasion ('v' group, 323 days) or both ('vm' group, 187 days).
• The 'm' group demonstrated better liver function and was identified as an independent prognostic factor (HR 0.50) in multivariable analysis.

Conclusions:

• Unresectable HCC with extrahepatic metastasis but no vascular invasion represents a distinct clinical entity.
• This subgroup warrants consideration as a novel staging category for guiding systemic treatment decisions.
• Optimizing systemic therapy for this specific HCC subgroup may improve patient outcomes.