Real-World Systemic Treatment Patterns, Survival Outcomes, and Prognostic Factors in Advanced Hepatocellular Carcinoma: A 15-Year Experience from a Low-Resource Setting

<b>Background:</b> The treatment landscape for advanced hepatocellular carcinoma (HCC) has evolved significantly recently; however, access to novel agents remains limited because of high costs. This study aimed to evaluate the systemic treatment patterns and survival outcomes for advanced HCC across different systemic treatment sequences under real-world resource constraints. <b>Methods:</b> This retrospective study was conducted at a tertiary center in Southern Thailand. The medical records of patients (<i>n</i> = 330) with advanced HCC treated with systemic therapy between 2010 and 2024 were reviewed. Outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Prognostic factors for OS were investigated. <b>Results:</b> First-line therapies included tyrosine kinase inhibitor (TKI; 69.7%), chemotherapy (23.3%), immunotherapy (IO)/targeted therapy (3.6%), dual IO (1.8%), and IO monotherapy (1.5%). The median OS, PFS, and ORR for each cohort were 7.2, 5.2, 10.9, 8.5, and 8.6 months; 3.94, 3.22, 3.48, 6.19, and 2.69 months; and 9.6%, 10.4%, 16.7%, 0%, and 20.0%, respectively. OS improved with increasing lines of therapy (4.5, 12.2, 19.4, and 40.7 months for one to four lines, respectively). Portal vein tumor thrombus, ascites, elevated bilirubin level, high alpha-fetoprotein level, and poor Eastern Cooperative Oncology Group performance status were associated with poor prognosis; multiple treatment lines and overweight status were associated with improved OS. <b>Conclusions:</b> In this large real-world cohort, TKIs remained the mainstay effective treatment option because of limited access to IO-based regimens. Sequential systemic therapy significantly improved survival, emphasizing the importance of preserving treatment eligibility and multidisciplinary team involvement. Chemotherapy could be considered a viable option in resource-limited settings.