Comparison of the Effects of Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma between Patients with and without Extrahepatic Metastases

Background/Aims: Sorafenib is a standard treatment for advanced hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] stage C). However, transarterial chemoembolization (TACE) has also been widely used as a treatment for patients with advanced HCC, even if they have extrahepatic metastases (EHM). The aim of this study was to determine the efficacy of TACE for advanced HCC patients with EHM upon initial diagnosis, as compared with those patients without EHM. Methods: This cohort study involved consecutive patients who underwent TACE as an initial treatment for advanced HCC. One hundred seventy-seven patients with EHM (the EHM group) and 205 with portal vein invasion without EHM (the non-EHM group) were included. A survival analysis was performed to compare overall survival between the two groups. Results: The mean age was 54.5 +/- 9.9 years, and median follow-up duration was 13.1 months (range, 0.5-111.0). Overall survival was significantly shorter in the EHM group than the non-EHM group (median, 8.3 vs. 19.1 months; P<0.001). A multivariate analysis showed that the presence of EHM was an independent poor prognostic factor for shorter overall survival (adjusted hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P<0.001) after adjustment for Child-Pugh classification, intrahepatic tumor T classification, tumor response to TACE, and serum alpha-fetoprotein level. Patients administered TACE and systemic therapy demonstrated a better survival rate than those administered TACE alone in both the EHM (median, 13.5 vs. 7.2 months) and non-EHM groups (median, 27.9 vs. 18.2 months) (both, P<0.05). Conclusions: The prognosis of advanced HCC patients with EHM is significantly worse than those without EHM administered repeated TACE treatments, even if their tumor stage was similar to BCLC stage C. These results suggest that EHM presence means aggressive tumor biology and that BCLC stage C might be subclassified according to EHM presence.