A NEW study suggests that the pattern of recurrence, rather than recurrence itself, is the key determinant of long-term outcomes following curative resection for hepatocellular carcinoma (HCC).
HCC can be effectively treated with surgical resection when detected at an early stage, but postoperative recurrence remains common and clinically challenging. In particular, recurrence beyond the Milan criteria, used to guide liver transplantation eligibility, is associated with limited treatment options and poor prognosis. However, the clinical impact of different recurrence patterns after resection has not been fully clarified.
In this retrospective analysis, researchers evaluated 351 patients who underwent curative resection for HCC as their initial treatment between January 2011 and December 2020. Patients were stratified into three groups based on recurrence pattern during follow-up: no recurrence, recurrence within the Milan criteria, and recurrence beyond the Milan criteria. Treatments for recurrent disease and long-term outcomes were compared, and predictors of recurrence beyond the Milan criteria were assessed.
Recurrence Patterns After Curative Resection for Liver Cancer
Over a median follow-up period of 69 months, 37.6% of patients experienced no recurrence, 25.6% had recurrence within the Milan criteria, and 36.8% developed recurrence beyond the Milan criteria. Survival outcomes differed markedly between groups. Notably, patients with recurrence within the Milan criteria had overall survival comparable to those with no recurrence, suggesting that these recurrences can often be managed effectively with available treatments.
In contrast, patients with recurrence beyond the Milan criteria had significantly worse outcomes, with a more than fivefold increase in mortality risk compared with those without recurrence. These findings highlight the aggressive nature and limited treatability of disease that recurs outside transplant eligibility criteria.
Risk Factors for Aggressive Recurrence After HCC Resection
The study also identified several risk factors associated with recurrence beyond the Milan criteria, including male sex, elevated alfa-fetoprotein levels (>500 ng/mL), high PIVKA-II levels (>400 mAU/mL), the presence of two or more tumours, portal vein invasion, and underlying liver cirrhosis. Overall survival declined progressively as the number of these risk factors increased, indicating their potential value for postoperative risk stratification.
The authors conclude that recurrence pattern is a more meaningful predictor of prognosis after curative resection for HCC than recurrence alone. They emphasise the need for further research into perioperative and adjuvant treatment strategies for patients at high risk of recurrence beyond the Milan criteria, with the goal of improving long-term survival in this vulnerable population.
Reference
Terashima T et al. Clinical Impact of Recurrence Beyond the Milan Criteria After Curative Resection of Hepatocellular Carcinoma. Hepatol Res. 2025;doi: 10.1111/hepr.70099
