Changing Treatment Landscape of Hepatocellular Carcinoma: A Real-World Retrospective Analysis of Treatment Algorithms and Outcomes of Patients over 10 Years.

Abstract

Background: Hepatocellular carcinoma is one of the most common cancers worldwide and the third leading cause of cancer-related mortality. The therapeutic landscape of hepatocellular carcinoma, especially systemic therapies, is constantly changing and characterized by a multimodal approach.

Objective: The aim of this study was to investigate whether and how treatment sequencing according to tumor stage and liver function has changed over time and if the introduction of new therapeutic options has led to improved survival rates.

Methods: Therapy concepts were retrospectively recorded and evaluated in a cohort of 1288 patients with hepatocellular carcinoma with a first diagnosis between January 2013 and December 2022 who were divided into two cohorts with a cut-off for dividing in 2020 owing to the approval of atezolizumab and bevacizumab for the treatment of hepatocellular carcinoma by the European Medicines Agency (Cohort A initial diagnosis 2013-19, Cohort B initial diagnosis 2020-22). All patients were treated at Hannover Medical School, Germany.

Results: Baseline characteristics differed significantly between cohorts, with Cohort B presenting at earlier tumor stages and with better preserved liver function. Across all treatment modalities, liver function emerged as the primary determinant of prognosis, independent of tumor stage and performance status. Over time, a treatment shift from transarterial chemoembolization towards systemic therapies was observed. Median overall survival from initial diagnosis did not differ between cohorts. In unadjusted analyses, patients treated with immune checkpoint inhibitor-based regimens demonstrated longer median overall survival compared with those receiving tyrosine kinase inhibitors. However, after multivariable adjustment for baseline imbalances, no independent survival difference between treatment groups remained.

Conclusions: This study provides a detailed longitudinal assessment of evolving treatment patterns and outcomes, highlighting a clear shift in therapeutic strategies over time with the increasing adoption of systemic therapies. Despite evolving treatment strategies and increased use of systemic therapies, liver function remained the dominant prognostic factor across treatment settings. Observed survival differences between treatment modalities were strongly influenced by baseline patient characteristics and treatment selection.