Transcatheter Arterial Chemoembolization (TACE) in Hepatocellular Carcinoma (HCC): The Role of Angiogenesis and Invasiveness

OBJECTIVE Although transcatheter arterial chemoembolization (TACE) is effective in hepatocellular carcinoma (HCC), it is not considered a curative procedure. Among the factors potentially interfering with its effectiveness is a hypothetical neoangiogenic reaction due to ischemia. In our study, we evaluated the changes in the levels of two angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [b-FGF]) and one parameter of invasiveness (urokinase-type plasminogen activator [uPA]) in patients treated with TACE. METHODS Three blood samples were provided from 71 HCC patients undergoing TACE: before TACE (t0), after 3 days (t1), and after 4 wk, when they had spiral computed tomography (sCT) scanning (t2). The referring radiologists blindly evaluated tumor burden and vascularization at t0 and residual activity at t2. The choice of TACE as treatment was based on the American Association for the Study of Liver Diseases (AASLD) guidelines. RESULTS Complete response at sCT was recorded in 27% of patients; mean survival was 35 months (confidence interval [CI] 31–40) and the 4-yr survival was 57%. VEGF levels were significantly correlated with the number of nodes and were higher in nonresponders at t2 (P= 0.01); below-median VEGF levels predicted a longer survival (P= 0.008). b-FGF correlated with VEGF, tumor size, vascularization, and residual activity, showing a borderline correlation with survival. uPA correlated with tumor size and VEGF. VEGF was singled out in the Cox multivariate analysis as an independent predictor of survival. CONCLUSIONS When TACE is not totally effective, it may induce a significant neoangiogenetic reaction, as suggested by an increase in VEGF and b-FGF following treatment; this affects patient survival. VEGF emerges as the most reliable prognostic parameter, so it could be measured for judging TACE efficacy. Finally, antiangiogenic drugs may be indicated in TACE-treated HCC.