Hepatectomy Versus Sorafenib in Advanced Non-Metastatic Hepatocellular Carcinoma: A Real-Life Multicentric Weighted Comparison

Objective: The aim of the study was to compare surgery (SURG) vs sorafenib (SOR) regarding the overall survival (OS) and progression-free survival (PFS) in a real-world clinical scenario. Background data: The treatment for advanced non-metastatic hepatocellular carcinoma (HCC) belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. Methods: BCLC C patients without extra-hepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, while sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the two groups. Results: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. ECOG-PS, presence of cirrhosis, steatosis, Child-Pugh grade, HBV and HCV, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG=374 and SOR=263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (p < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS =0 and ECOG-PS >0, and by the intra-hepatic location of portal vein invasion. At Cox regression, sorafenib treatment (HR 4.436; 95%CI 3.19-6.15; p < 0.001) and Charlson Index (HR 1.162; 95%CI 1.06-1.27; p = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (p = 0.007). Conclusions: In BCLC C patients without extra-hepatic spread but with intra-hepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.