Anatomical resection is associated with reduced early recurrences in HCC: A machine learning analysis.

Background & Aims: Anatomical resection (AR) for hepatocellular carcinoma (HCC) could improve micrometastasis eradication and reduce their recurrence, but conflicting findings suggest heterogeneous treatment effects (HTEs). This study investigated the heterogeneity in the association between AR and decreased postoperative HCC recurrence. Methods: Between January 2014 and December 2021, preoperative imaging and clinicopathologic data from 1,859 patients with HCC were retrospectively reviewed from seven hospitals in China. Using data from six centers (the development set), causal forest modeling was performed to estimate subgroups with different HTEs after propensity score matching (PSM) for multiple clinical-radiological covariates. Differences in early recurrence risk (within 2 years) and recurrence-free survival (RFS) between AR and non-AR were evaluated in identified subgroups. Data from the remaining center were treated as the validation set. Results: The development set included 1,496 patients, of whom 1,266 were identified after PSM; the validation set included 363 patients. The causal forest model identified tumor size ≤5 cm and non-smooth tumor margins on preoperative imaging as effect modifiers distinguishing those who benefited differentially from AR in the development set. AR achieved a 16.76% absolute reduction in early recurrence risk (95% CI, 3.39-29.48) compared with non-AR in patients with tumors ≤5 cm and non-smooth margins (393/1,266; 31.0%), along with improved RFS (hazard ratio [NAR Conclusions: HTEs of AR occurred in patients with single HCC. Tumor size ≤5 cm and non-smooth tumor margin might could be used to identify patients with HCC who are likely to derive benefit from AR. Impact and implications: Causal forest modeling enables the detection of HTEs of AR in patients with HCC based on multiple clinical-radiological characteristics. Radiological tumor size ≤5 cm and non-smooth tumor margins were identified as significant modifiers and should be taken into consideration when selecting between AR and non-AR. Based on these findings, over 30% of the study population who underwent non-AR might have experienced a reduced risk of early recurrence and improved RFS if AR had been performed, thereby supporting the importance of personalized selection of the optimal hepatectomy type in patients with HCC.