Tyrosine kinase inhibitors combined with PD-1 inhibitors reduce peritoneal metastasis risk for patients with ruptured HCC receiving TACE/TAE: a multicenter retrospective study.

[PURPOSE] This study aimed to evaluate whether the combination of tyrosine kinase inhibitors (TKIs) and PD-1 inhibitors can reduce the risk of peritoneal metastasis (PM) in patients with ruptured hepatocellular carcinoma (HCC) after transcatheter chemoembolization/embolization (TACE/TAE).

[MATERIALS AND METHODS] This study included 163 patients with ruptured HCC who received TACE/TAE at 4 centers from June 2015 to June 2023. Patients were categorized into two groups based on their treatment: the combination group, which received TKIs plus PD-1 inhibitors, and the TACE/TAE group, which did not. Propensity score matching (PSM) analysis was performed in a ratio of 1:2 to reduce bias between the groups. The PM rate, overall survival (OS) and the occurrence of adverse events were analyzed and compared between the two groups. Moreover, the independent factors associated with PM were further evaluated.

[RESULTS] The median follow-up duration was 801 days [95% confidence interval (CI): 720.2-925.7]. After PSM, the combination and TACE/TAE groups comprised 45 and 90 patients, respectively. A significant difference was observed in the peritoneal PM rate (combination group: 6.7% vs. TACE/TAE group: 23.3%, P = 0.032). The corresponding 3-, 6-, 12-, and 24-month PM cumulative incidence was 5.6%, 15.7%, 22.5%, and 24.1% in the TACE/TAE group, and 0%, 0%, 4.9%, and 7.7% in the combination group, respectively (P < 0.001). The combination group exhibited a significantly longer median OS compared to the TACE/TAE group (OS:566 days vs. 120 days, P < 0.001). The multivariate competing risk analysis identified hepatitis B virus (HBV) infection [subdistribution hazard ratio (SHR), 0.420; 95% CI: 0.188-0.939; P = 0.035), Barcelona Clinic Liver Cancer stage C (BCLC C) (SHR, 0.228; 95% CI: 0.059-0.874; P = 0.031), and combination therapy (SHR, 0.267; 95% CI: 0.082-0.866; P = 0.028) as the independent factors for PM. More adverse events were witnessed in the combination group compared with the monotherapy group, most of which were tolerable and manageable.

[CONCLUSIONS] The combination of TKIs and PD-1 inhibitors reduced the risk of PM compared with TACE/TAE in patients with ruptured HCC. Also, PM was less likely to occur in patients with HBV-related and BCLC C ruptured HCC.