Abstract:Objective To explore the therapeutic effects of transcatheter arterial chemoembolization（TACE）on unresectable middle advanced stage primary liver cancer（PLC）and its different combination regimens with hepatic arterial infusion chemotherapy（HAIC），molecular targeted therapy and immunotherapy. Methods Clinical data of 88 patients with unresectable middle-advanced stage PLC who were treated with TACE at the Hepatopancreatobiliary Medicine Center of The First Affiliated Hospital of Shandong Second Medical University from January 2020 to November 2024 were collected retrospectively，including general information，disease progression，and treatment modalities. According to different treatment schemes，the patients were classified into TACE alone group，dual-therapy group，triple-therapy group，and quadruple-therapy group. Treatment responses and prognoses of the four groups were evaluated. Results Among the 88 patients with middle-advanced stage PLC，18 received TACE monotherapy；22 received dual therapy（8 cases of TACE + HAIC，14 cases of TACE + molecular targeted therapy）；34 received triple therapy（4 cases of TACE + HAIC + molecular targeted therapy，30 cases of TACE + molecular targeted therapy + immunotherapy）；and 14 received quadruple therapy（TACE + HAIC + molecular targeted therapy + immunotherapy）. Six months after treatment，there was a statistically significant difference in the Objective response rates（ORRs）among the groups. Both ORRs of the triple-therapy group and quadruple-therapy group were higher than that of the monotherapy group（P < 0.05），while there was no statistically significant difference in the disease control rates（DCRs）among the groups（P > 0.05）. The overall survival（OS）of all patients ranged from 4 to 48 months，with a median OS of 16 months. The median OS was 7.5 months in the monotherapy group，13.0 months in the dual-therapy group，25.0 months in the triple-therapy group，and 38.5 months in the quadruple-therapy group，with statistically significant difference among the groups（P < 0.05）. Conclusion For patients with unresectable middle-advanced stage PLC，the comprehensive treatment strategy of TACE combined with molecular targeted therapy and immunotherapy can significantly improve the treatment efficacy and prognosis.