Microvascular invasion does not predict long-term survival in hepatocellular carcinoma up to 2 cm: reappraisal of the staging system for solitary tumors

Abstract

Background: Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm.

Methods: In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed.

Results: In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27-1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11-1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01-1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups-HCC ≤2, >2 cm without MVI, and HCC >2 cm with MVI-significant between-group survival difference was observed (p < 0.0001).

Conclusions: Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm).

FIG. 1

Survival of patients with solitary hepatocellular carcinoma according to current staging systems. a American Joint Committee on Cancer 7th edition. b Liver Cancer Study Group of Japan 5th edition. c Barcelona Clinic Liver Cancer staging system

FIG. 2

Survival of patients with solitary hepatocellular carcinoma according to presence of microvascular invasion (MVI). a Tumor size 0–2 cm. b Tumor size >2 cm

FIG. 3

Survival of patients with solitary hepatocellular carcinoma according to tumor size and microvascular invasion (MVI) and new classification of hepatocellular carcinoma (HCC). a Comparison of survival according to size cutoff value of 2 cm and MVI. b Comparison of new classification for solitary tumor and current classification of multiple HCC. c Proposed new classification by stage (stages as outlined in Table 3)