Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma

Simple Summary This study aimed to investigate the safety and long-term survival outcomes of salvage liver resection in patients with initially unresectable hepatocellular carcinoma (HCC) who had undergone triple combination conversion therapy (TACE/HAIC + TKIs + ICIs). While hepatectomy following conversion therapy exhibited elevated incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure, and Clavien-Dindo grade IIIa complications compared to pure hepatectomy, their safety profiles remained acceptable when appropriate medical interventions were administered. Patients with initially unresectable HCC, who successfully underwent conversion resection, demonstrated comparable overall survival (OS) and recurrence-free survival (RFS) to patients with initially resectable HCC.Abstract Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.