Pre- and postoperative predictors of extrahepatic recurrence after curative resection for hepatocellular carcinoma

Background: The factors associated with extrahepatic recurrence (EHR) after curative resection for hepatocellular carcinoma (HCC) have rarely been investigated. This study examined the pre- and postoperative predictors of EHR after curative resection in HCC patients over a ten-year follow-up period. Methods: A retrospective review was conducted on treatment-naïve HCC patients who underwent curative resection between 2004 and 2019 at four tertiary hospitals in South Korea. The cohort of 1,069 patients was divided into a derivation cohort (n = 683) and a validation cohort (n = 386) based on participating institutions. Results: In the derivation cohort, the mean age was 59.8 years, and 85.7% were male. The majority of patients (98.7%) had compensated liver cirrhosis, and chronic hepatitis B was the prevalent etiology (72.9%). EHR developed in 107 patients (15.7%) and was associated with younger age, advanced tumor stages, and histological features including larger tumor size, a higher number of tumors, the presence of microvascular invasion, serosal nvasion, intrahepatic metastasis, and necrosis. According to multivariable Cox regression analyses, younger age, a higher modified Union for International Cancer Control (UICC) stage, exceeding the Milan criteria, and an albumin–bilirubin (ALBI) grade ≥ 2 were independently significant preoperative factors associated with EHR. Similarly, age, tumor number, the presence of microvascular invasion, necrosis, exceeding the Milan criteria, and an ALBI grade ≥ 2 were independently significant postoperative factors. Kaplan–Meier plots clearly differentiated EHR-free survival among the risk groups stratified by our EHR-preop and EHR-postop models. The EHR-preop and EHR-postop models, developed in the derivation cohort, were applied to the validation cohort and showed clear separation among risk groups. Conclusion: Our study developed and validated predictive models (EHR-preop and EHR-postop) to identify the risk of EHR after curative HCC resection. The models could potentially enhance clinical decision-making by identifying patients at elevated EHR risk thus advancing personalized HCC care.