Background: Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S.

Methods: The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval). Results A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35-0.56), hepatic resection (HR = 0.35, 95% CI: 0.33-0.37), and transplantation (HR = 0.14, 95% CI: 0.13-0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages.

Conclusions: Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.