Pattern of progression in advanced hepatocellular carcinoma treated with immunotherapy.

Abstract

510 Background: Radiological progression patterns have long been recognized as prognostic indicators in hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors. However, their impact in the era of immune checkpoint inhibitors (ICIs) remains underexplored. This study investigates the prognostic significance of progression patterns in advanced HCC patients receiving ICI-based therapies. Methods: We conducted a retrospective cohort study of 293 patients with radiologically confirmed disease progression following ICI treatment at Queen Mary Hospital between January 2015 and September 2023. Progression patterns were categorized as intrahepatic growth, new intrahepatic lesions, extrahepatic growth, and new extrahepatic lesions. Multivariate Cox regression analyses were performed to assess their impact on overall survival (OS) and post-progression survival (PPS), adjusting for ALBI score and AFP levels. Results: Intrahepatic growth was significantly associated with poorer OS in both the first-line (HR 1.905, 95% CI 1.268–2.861; p = 0.002) and overall cohorts (HR 1.632, 95% CI 1.203–2.213; p = 0.002). Extrahepatic growth consistently predicted reduced OS (HR 1.728, 95% CI 1.305–2.290; p < 0.001) and PPS (HR 1.771, 95% CI 1.330–2.360; p < 0.001) across all treatment subgroups. New extrahepatic lesions were associated with inferior OS in the overall (HR 1.402, 95% CI 1.054–1.865; p = 0.020) and first-line populations (HR 1.556, 95% CI 1.060–2.285; p = 0.024), and with poorer PPS in patients receiving ICI combined with anti-VEGF agents (HR 1.842, 95% CI 1.089–3.116; p = 0.023). In contrast, new intrahepatic lesions did not demonstrate significant prognostic impact on PPS in adjusted analyses (HR 0.938, 95% CI 0.708–1.243; p = 0.658). Conclusions: In advanced hepatocellular carcinoma treated with immune checkpoint inhibitors, intrahepatic growth and extrahepatic expansion—particularly of pre-existing lesions—are independently associated with poorer overall and post-progression survival. These findings highlight the prognostic relevance of radiological progression patterns in the immunotherapy era and suggest that both intra- and extrahepatic disease dynamics warrant close surveillance. Integrating systemic therapies with timely locoregional interventions may offer a path to improved outcomes in this patient population.