Tumor capsule status modifies the survival impact of anatomical versus non-anatomical hepatectomy in early-stage hepatocellular carcinoma: a multicenter retrospective study

BACKGROUND: The oncologic superiority of anatomical resection (AR) over non-anatomical resection (NAR) for hepatocellular carcinoma (HCC) remains controversial, and the extent to which tumor capsule integrity modifies the survival benefit of AR has not been well defined. METHODS: This multicenter retrospective study included 1,958 patients with early-stage HCC who underwent curative-intent hepatectomy across seven institutions. Patients were classified according to hepatectomy type (AR vs. NAR) and tumor capsule status (complete, incomplete, or absent). Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. Ordered interaction analyses were conducted to assess effect modification between hepatectomy method and tumor capsule status. RESULTS: In IPTW-weighted analyses, NAR was independently associated with worse OS (HR 1.46, 95% CI 1.27-1.67; P < 0.001) and RFS (HR 1.24, 95% CI 1.12-1.38; P < 0.001) compared with AR. Tumor capsule status showed a graded association with survival outcomes, with incomplete and absent capsules associated with progressively poorer OS and RFS. Importantly, a significant ordered interaction between hepatectomy method and tumor capsule status was observed for both OS (HR 1.65, 95% CI 1.35-2.01; P < 0.001) and RFS (HR 1.45, 95% CI 1.24-1.70; P < 0.001). Stratified analyses demonstrated no significant survival difference between AR and NAR in patients with complete capsule, whereas AR conferred a pronounced survival advantage in patients with absent capsule. CONCLUSIONS: Anatomical resection is associated with improved oncologic outcomes in early-stage HCC overall; however, this survival benefit is strongly modified by tumor capsule status. These findings suggest that tumor capsule status may serve as an important stratification factor when evaluating the extent of liver resection.