Combining Transarterial Chemoembolization with Sorafenib Improves Survival in Selected Patients with Hepatocellular Carcinoma and Extrahepatic Spread: A Multicenter Real-World Study

Yue Yuan,1,* Yu Qiao,2,3,* Yejing Zhu,2,* Ping Guo,4 Jiakun Gou,1 Kai Liu,1 Linqian Wang,2,5 Shoujie Zhao,2 Yongchao Zhang,6 Yunjie Liu,1 Enxin Wang,1 Lei Liu2 1Department of Digestive Diseases, Air Force Hospital of Western Theater Command, PLA, Chengdu, People’s Republic of China; 2Department of Infectious Diseases, Xijing Hospital, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Department of Gastroenterology, Yanan University Affiliated Hospital, Yan’an, People’s Republic of China; 4Center for Disease Control and Prevention of Western Theater Command, PLA, Chengdu, People’s Republic of China; 5Northwest University Medical College, Xi’an, People’s Republic of China; 6Department of Medical Affairs, Air Force Hospital of Western Theater Command, PLA, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Enxin Wang, Department of Digestive Diseases, Air Force Hospital of Western Theater Command, PLA, Chengdu, 610083, People’s Republic of China, Email [email protected] Lei Liu, Department of Infectious Diseases, Xijing Hospital, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China, Email [email protected]: The prognosis of hepatocellular carcinoma with extrahepatic spread (HCC-EHS) remains poor. While systemic therapy is standard, intrahepatic progression often drives mortality. This study evaluated whether combining transarterial chemoembolization (TACE) with sorafenib (TACES) improves outcomes versus TACE alone in HCC-EHS.Methods: In this multicenter, retrospective study, 423 HCC-EHS patients (Child-Pugh A) were categorized into TACE-alone (n = 294) or TACES (n = 129) groups. The primary endpoint was overall survival (OS). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding. Radiological response was assessed per mRECIST.Results: After IPTW adjustment, the TACES group demonstrated significantly superior tumor response, with higher objective response (33.3% vs 16.4%, p = 0.004) and disease control rates (63.2% vs 46.3%, p = 0.008) compared to the TACE-alone group. This translated into a significant survival benefit, with a median OS of 10.4 months for TACES versus 7.0 months for TACE alone (IPTW-adjusted hazard ratio: 0.68; 95% CI: 0.52– 0.88; p = 0.004). The survival advantage remained consistent in landmark analyses. Subgroup analyses indicated that the absolute benefit from combination therapy was most pronounced in patients with high intrahepatic tumor burden and preserved liver function.Conclusion: This real-world study demonstrates that in carefully selected patients with HCC-EHS, a combination of TACE and sorafenib provides significantly better tumor control and survival outcomes than TACE monotherapy. These findings suggest that an integrated therapeutic strategy, which aggressively manages the intrahepatic disease in conjunction with systemic therapy, can improve outcomes in this challenging-to-treat population and warrants validation in prospective studies. Keywords: hepatocellular carcinoma, transarterial chemoembolization, sorafenib, survival