A Clinical Study Of TACE Combined With Targeted Therapy And Immunotherapy To Prevent Postoperative Recurrence For Patients With HCC With MVI

Background and aims: Surgical resection was recognized as one of the most effective treatment modalities for hepatocellular carcinoma(HCC).However,the considerable recurrence rates of postoperative recurrence negatively impact patients’ survival time.Microvascular invasion(MVI)was widely recognized as a significant factor that has a substantial impact on postoperative recurrence and long-term survival in HCC.For patients with HCC with MVI,there was a lack of sufficient evidencebased medical data supporting postoperative adjuvant therapy.Therefore,this study aimed to explore the efficacy and safety of adjuvant transarterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptor-1(PD-1)inhibitors after hepatectomy to prevent postoperative recurrence in HCC patients with MVI.Methods: From January 2018 to May 2022,patients who were clinically diagnosed with HCC and underwent R0 resection at Nanchang University’s First Affiliated Hospital were included in the study.These patients were screened to identify those with postoperative pathologically confirmed HCC with MVI.The selected patients received either adjuvant TACE(PA-TACE)or adjuvant TACE combined with tyrosine kinase inhibitors(TKIs)and programmed cell death protein 1(PD-1)inhibitors(PA-TTP)after surgery.Confounding variables between the two groups were balanced using Propensity Score Matching(PSM).The Kaplan-Meier method and Log-Rank test were used to compare recurrence-free survival(RFS)between the two groups,overall survival(OS)with different relapse patterns,and other treatment modalities after recurrence.The COX proportional risk model was used to identify factors affecting RFS,and subgroup analysis was done for factors that might affect RFS.In addition,the differences in adverse events(AEs)between the two groups were compared.Results: The median RFS before PSM was 17.0 months [95% confidence interval(CI)7.3-26.7 months] in the PA-TACE group and not reached in the PA-TTP group(95% CI not reached),with no significant difference between the two groups(p =0.072).The recurrence-free rates at 6,12,and 24 months were 82.5%,60.7%,and 44.6%in the PA-TACE group and 95.2%,81.0%,and 68.3% in the PA-TTP group,respectively.After PSM,the median RFS in the PA-TACE group was 14.8 months(95%CI 7.7-21.8 months)and not reached in the PA-TTP group(95% CI not reached),and the RFS was better in the PA-TTP group than the PA-TACE group(p = 0.047).The recurrence-free rates at 6,12,and 24 months in the PA-TACE group were 88.2%,58.3%,and 44.7%,respectively,compared to 100%,87.5%,and 72.2% in the PA-TTP group.The COX multivariate analysis showed age < 50 years [hazard ratio(HR)3.086,95%CI 1.267-7.519,p = 0.013),number of tumors of 2(HR 5.854,95% CI 1.228-27.914,p = 0.027)and not combined with TKIs plus PD-1 inhibitors(HR 3.826,95% CI 1.242-11.793,p = 0.019)were independent risk factors for RFS.The results of the subgroup analysis showed that PA-TTP could provide better clinical benefits for patients with tumors ≥5cm in maximum diameter compared to the PA-TACE group.Regarding safety,although the PA-TTP group had more TKIs and PD-1 inhibitor-related AEs than the PA-TACE group,both were tolerable,and none were observed to have fatal-related AEs.Conclusion: For patients with HCC with MVI after radical resection,PA-TTP resulted in improved RFS,lower 6-,12-,and 24-month recurrence-free survival rates,and was more acceptable regarding AEs than PA-TACE.