Survival Outcomes Among Patients With Hepatocellular Carcinoma in a Large Integrated US Health System

Importance Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking. Objective To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US. Design, Setting, and Participants This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024. Exposures Patient demographic characteristics and disease factors. Main Outcomes and Measures All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type. Results Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio AHR, 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs lt;20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434). Conclusions and Relevance This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.