Impact of Anatomical Resection on Non-transplantable Recurrence Among Patients with Hepatocellular Carcinoma: An International Multicenter Inverse Probability of Treatment Weighting Analysis

Background: Among patients with hepatocellular carcinoma (HCC), the impact of anatomic resection (AR) versus non-anatomic resection (NAR) on non-transplantable recurrence (NTR) remains poorly defined. We sought to compare the risk of NTR among patients treated with AR versus NAR as the primary surgical strategy for HCC. Patients and Methods: Patients with HCC within Milan criteria who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. The inverse probability of treatment weighting (IPTW) method was utilized to compare short- and long-term outcomes among patients undergoing AR versus NAR. Results: Among 1038 patients, 747 (72.0%) patients underwent AR, while 291 (28.0%) patients underwent NAR. After IPTW adjustment, patients who underwent AR had better 5-year recurrence-free survival than individuals treated with NAR (63.9 vs. 52.0%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.62–0.99); however, there was no difference in 5-year overall survival (80.2 vs. 75.6%; HR 0.76; 95% CI 0.55–1.05). Notably, individuals who underwent AR were less likely to have a NTR versus individuals treated with NAR (3-year NTR 9.8 vs. 14.4%; HR 0.62; 95% CI 0.40–0.96). In particular, AR was associated with a lower risk of NTR among patients with a medium tumor burden score (TBS) (HR 0.53; 95% CI 0.28–0.99), while the benefit among patients with a low TBS was less pronounced (HR 0.73; 95% CI 0.40–1.32). Conclusions: AR was associated with a lower risk of NTR and improved recurrence-free survival (RFS) among patients with HCC, especially individuals with higher TBS. An anatomically defined surgical approach should be strongly considered in patients with a higher HCC tumor burden.