Abstract
BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with a high recurrence rate after resection. This study investigates the efficacy of postoperative anti-PD-1 antibody therapy on overall survival (OS) and recurrence-free survival (RFS) in HCC patients, with a particular focus on those positive for vessels encapsulating tumor clusters (VETC), a marker of aggressive disease behavior and high recurrence risk. METHODS: This prospective observational study analyzed data from HCC patients who underwent curative liver resection between June 2015 and June 2022. Patients were divided into two groups based on postoperative anti-PD-1 antibody treatment. Propensity score matching (PSM) was employed to balance baseline characteristics. Kaplan-Meier analysis was used to assess OS and RFS, while Cox regression models identified prognostic factors. Subgroup analyses focused on the impact of VETC status on treatment outcomes. RESULTS: A total of 388 patients were included, with 148 receiving anti-PD-1 therapy. Both OS and RFS were significantly improved in the anti-PD-1 group before and after PSM. Specifically, postoperative anti-PD-1 therapy yielded notably better survival outcomes in VETC-positive patients. In contrast, no significant difference in OS (HR = 0.74 [0.53-1.02], P = 0.069) or RFS (HR = 0.79 [0.56-1.12], P = 0.184) was observed between treatment groups among VETC-negative patients, indicating that VETC status may guide postoperative immunotherapy. Cox regression analysis identified VETC as a risk factor for OS and RFS in HCC patients, while anti-PD-1 therapy emerged as a protective factor for both outcomes, particularly for high-risk, VETC-positive patients. CONCLUSIONS: Postoperative anti-PD-1 therapy significantly improves OS and RFS in HCC patients, especially those with VETC positivity, highlighting its potential as an effective adjuvant treatment for high-risk patients. VETC may serve as a valuable prognostic biomarker, aiding in the development of postoperative immunotherapy strategies to improve long-term outcomes in HCC.