Diagnostic Pathways and Outcomes of First-Line Atezolizumab plus Bevacizumab in Patients with Locoregional Therapy–Ineligible Hepatocellular Carcinoma at Initial Diagnosis

Introduction: Real-world evidence is limited for patients with unresectable hepatocellular carcinoma (HCC) who are ineligible for locoregional therapy (LRT) at initial diagnosis. We examined diagnostic pathways and outcomes of first-line atezolizumab plus bevacizumab (Atz+Bev), with a focus on de novo LRT-ineligible HCC. Methods: We retrospectively analyzed 107 systemic therapy–naïve patients with unresectable HCC who received Atz+Bev as first-line systemic therapy. Patients were categorized into LRT-naïve (n = 55) and LRT-experienced (n = 52) groups. Diagnostic pathways, baseline characteristics, and treatment outcomes were evaluated. Results: Among LRT-naïve patients, 34.5% presented with HCC-related symptoms, whereas the majority were diagnosed incidentally during outpatient care for metabolic comorbidities, often triggered by mild liver enzyme abnormalities. In this group, clinically meaningful disease control was observed despite a high intrahepatic tumor burden at presentation, with an objective response rate of 41.8% and a disease control rate of 87.3%. Median progression-free survival was 11.7 months. Clinical outcomes were generally comparable between the LRT-naïve and LRT-experienced groups. Conclusion: Atz+Bev provides clinically meaningful disease control in patients presenting with de novo LRT-ineligible unresectable HCC. The frequent incidental mode of diagnosis highlights opportunities to strengthen risk stratification and surveillance in high-risk metabolic liver disease.