Atezolizumab Plus Bevacizumab Treatment for Patients With Hepatocellular Carcinoma in the Barcelona Clinic Liver Cancer B2 Stage

BACKGROUND AND AIM: The optimal treatment strategy for patients with intermediate-stage hepatocellular carcinoma beyond the up-to-seven criteria (Barcelona Clinic Liver Cancer B2) remains uncertain. Although transarterial chemoembolization has long been the standard of care, its efficacy is limited in this subgroup, and systemic therapies have recently been introduced. We aimed to explore treatment modalities associated with survival beyond that predicted by a previously validated prognostic model. METHODS: We retrospectively analyzed 113 patients diagnosed with BCLC-B2 stage hepatocellular carcinoma between 2017 and 2024. Predicted survival was calculated using a previously established prognostic model, and treatment benefits were evaluated by comparing observed survival with predicted outcomes. Logistic and linear regression analyses were performed to identify factors associated with survival gain. RESULTS: The median observed survival was 26.0 months, compared with a model-predicted survival of 24.7 months. Treatment with atezolizumab plus bevacizumab was significantly associated with survival exceeding model predictions (odds ratio: 3.77, p = 0.0065). Linear regression analysis confirmed that atezolizumab plus bevacizumab was independently associated with a greater survival benefit (β = 0.192, p = 0.0084). Subgroup analysis demonstrated that this association was particularly pronounced in patients with high tumor burden (tumor number plus size ≥ 11), whereas no significant associations were observed for lenvatinib, STRIDE, or cabozantinib. CONCLUSIONS: Atezolizumab plus bevacizumab was associated with survival beyond that predicted by a prognostic model in patients with BCLC-B2 stage hepatocellular carcinoma, particularly those with high tumor burden. These findings should be considered exploratory and associative rather than evidence of a causal treatment effect.