Comparison of Milan versus up-to-seven criteria for liver resection in hepatocellular carcinoma: a multi-center study on risk factors and long-term outcomes.

PURPOSE: This multi-center study aimed to evaluate the clinical validity of the "up-to-seven" criteria (sum of tumor number and largest diameter ≤ 7) as an expanded threshold for curative liver resection in hepatocellular carcinoma (HCC), comparing its outcomes with the established Milan criteria and identifying independent prognostic factors.

METHODS

A retrospective analysis was conducted on 264 consecutive HCC patients who underwent R0 resection. Patients were stratified into up-to-seven compliant (n = 219) and non-compliant (n = 45) cohorts. The compliant group was further divided into Milan compliant (n = 167) and "Milan non-compliant" (beyond Milan but within up-to-seven, n = 52) subgroups for comparative survival analysis. Overall survival (OS) and recurrence-free survival (RFS) were compared using Kaplan-Meier analysis. Cox regression was used to identify independent prognostic factors within the up-to-seven compliant cohort.

RESULTS

Patients within the up-to-seven criteria had significantly superior median OS (64.0 vs. 14.0 months, P = 0.020) and RFS (28.0 vs. 9.0 months, P = 0.023) compared to those beyond it. Critically, among up-to-seven compliant patients, there was no significant difference in OS (77.4 vs. 64.4 months, P = 0.648) or RFS (45.5 vs. 27.0 months, P = 0.883) between the Milan compliant and "Milan non-compliant" subgroups. Multivariate analysis identified age ≤ 60 years, open resection (vs. laparoscopic), and high histologic differentiation as independent prognostic factors for both OS and RFS. Recurrence analysis revealed distinct prognoses based on pattern: intrahepatic distant recurrence was associated with favorable median OS (81.2 months), while extrahepatic recurrence predicted poor outcomes (median OS: 28.0 months).

CONCLUSION

The up-to-seven criteria can safely expand surgical eligibility for HCC resection, offering long-term survival comparable to the Milan criteria. Laparoscopic resection and high tumor differentiation are associated with significantly improved outcomes. These findings advocate for the adoption of the up-to-seven criteria as a pragmatic surgical threshold, complemented by tailored risk stratification based on patient age, surgical approach, and tumor biology.