Clinical Impact of Recurrence Beyond the Milan Criteria After Curative Resection of Hepatocellular Carcinoma

ABSTRACT Aim Curative resection is possible for hepatocellular carcinoma (HCC) if the disease is detected early. However, recurrence patterns are variable, and it is difficult to control recurrent lesions in some cases. Methods We identified patients with HCC who underwent curative resection as their initial treatment between January 2011 and December 2020 and divided them into three groups according to recurrence pattern. Treatment of recurrent lesions and patient outcomes were compared between groups, and predictors of recurrence beyond the Milan criteria were identified. Results Data for 351 patients were analyzed. During a median observation period of 69.0 months, 132 patients (37.6%) had no recurrence, 90 (25.6%) had recurrence within the Milan criteria, and 129 (36.8%) had recurrence beyond the Milan criteria. Patient outcomes were comparable between the group with recurrence within the Milan criteria and the group without recurrence (hazard ratio 1.019 and P = 0.95). However, outcomes were significantly worse in the group with recurrence beyond the Milan criteria than in the group without recurrence (hazard ratio 5.059 and p < 0.01). Male sex, alfa fetoprotein > 500 ng/mL, PIVKA‐II > 400 mAU/mL, two or more tumors, portal vein invasion, and liver cirrhosis were identified as risk factors for recurrence beyond the Milan criteria after curative resection for HCC. Overall survival was stratified by number of risk factors. Conclusions This study suggests that the recurrence pattern determines the outcome after curative resection of HCC rather than recurrence itself. Further investigations are needed to develop perioperative treatment for patients with risk factors for recurrence beyond the Milan criteria.