Treatment Outcomes of Systemic Therapies for Infiltrative Hepatocellular Carcinoma.

Purpose: Outcomes in the treatment of unresectable infiltrative hepatocellular carcinoma (HCC) are poorly understood, and infiltrative HCC is generally underrepresented in clinical trials. The present study explored outcomes associated with the treatment of infiltrative HCC with various systemic therapies.

Patients and methods: We enrolled all patients with Barcelona Clinic Liver Cancer stage C infiltrative or multinodular HCC who received first-line systemic therapy between January 2015 and December 2021 at a single center. We compared baseline characteristics and treatment outcomes for the two HCC subtypes.

Results: In total, 260 patients were enrolled, 128 (49.2%) of whom had infiltrative HCC. Patients with infiltrative HCC were more likely to have macrovascular invasion (91.4% vs 68.2%, p < 0.001) but less likely to have extrahepatic spread (32.0% vs 54.5%, p < 0.001) than patients with multinodular HCC. In patients who received multikinase inhibitors alone, the time to treatment failure (TTF) and overall survival (OS) were similar for the 2 HCC subtypes. In patients who received immune checkpoint inhibitor (ICI)-based therapy, multivariate analyses revealed that infiltrative HCC was associated with shorter TTF (HR: 4.07, 95% CI: 2.13-7.79, p < 0.001) and poorer OS (HR: 3.27, 95% CI: 1.76-6.11, p < 0.001).

Conclusion: In patients receiving ICI-based therapy for HCC, infiltrative HCC was associated with poorer outcomes.