Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma

Background and Aim: Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization (TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE. Methods: We evaluated 264 patients with intermediate-stage HCC who underwent TACE between January 2006 and September 2009. We designated the development of vascular invasion or extrahepatic spread during follow up as "stage progression" (SP), and hypothesized that SP might be the surrogate end-point for TACE refractoriness. Results: The median follow up was 18.2months, and median number of TACE was 3.0 (range, 1-13). Median time-to-progression was 5.5months (95% confidence interval, 4.8-6.2), and median overall survival was 25.3months (95% confidence interval, 21.6-29.0). We classified the patients according to disease course as: no progressive disease (PD(-); n=33); PD without SP (PD(+)SP(-); n=113); PD followed by SP (PD→SP; n=47); and simultaneous PD and SP (PD&SP; n=64). PD(-) and PD(+)SP(-) groups showed no difference in overall survival, PD→SP group had worse overall survival than PD(-) and PD(+)SP(-) groups, and PD&SP group had the worst overall survival. The significant prognostic factors for SP-free survival were development of PD and need for three sessions of TACE during the first 6months. Conclusions: SP-free survival can be regarded as an end-point for TACE refractoriness. Development of progression or need for three sessions of TACE within the first 6months could be predictive of TACE refractoriness.