Microvascular Invasion and a Size Cutoff Value of 2 cm Predict Long-Term Oncological Outcome in Multiple Hepatocellular Carcinoma: Reappraisal of the American Joint Committee on Cancer Staging System and Validation Using the Surveillance, Epidemiology, and End-Results Database

Abstract

Introduction: For prognostication of hepatocellular carcinoma (HCC), the optimal size cutoff value and the significance of microvascular invasion (mvi) remain inconclusive. Objective: This study sought to revisit the inconclusive components of current American Joint Committee on Cancer (AJCC) staging system and to develop a new practical prognostication model for patients with HCC based on 2 large cohorts. Method: In 1,175 patients who underwent resection for HCC (training cohort), prognostic significance of mvi, and optimal size cutoff value were revisited and a new staging model was established. Then, its performance was validated using 5,249 patients derived from a population-based database (validation cohort). Results: The optimal size cutoff value was 2 cm in multiple HCC, similar to that for solitary HCC. Multivariate analyses confirmed that mvi, a size >2 cm, and multiple lesions were independent predictors with similar weights for disease-specific survival. Based on these results, earlier stages of HCC were reclassified according to the number of the following factors: multiple tumors, >2 cm in diameter, and presence of mvi. Also, given the similar prognosis of Stages IIIB and IVA according to the AJCC 8th edition, these groups were reclassified into the same stage. This new staging model had a better performance than the AJCC 8th edition in both training cohort (c-statistics, 0.648 vs. 0.629) and the validation cohort (c-statistics, 0.646 vs. 0.645) regardless of the presence of cirrhosis. Conclusions: Inclusion of a size cutoff value of 2 cm and mvi could reclassify the current version of the AJCC staging system and offer an alternative prognostication model using a single size-cutoff value of HCC.