Predictors of extrahepatic recurrence after transarterial chemoembolization as first-line therapy for hepatocellular carcinoma

Introduction The literature regarding the risk of progression to extrahepatic disease and clinical factors associated with the development of metastases in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is sparse. Aim We aimed to assess the incidence of extrahepatic recurrence and to identify clinically relevant risk factors for the development of metastases in patients with HCC undergoing TACE as first-line treatment. Materials and Methods From the Italian Liver Cancer (ITA.LI.CA) database, data of 981 HCC patients undergoing TACE as first-line treatment were retrieved and retrospectively analyzed. Incidence of extrahepatic recurrence was compared between two groups according to the diameter of the largest liver lesion at the time of TACE (HCC ≤ 3 cm vs. HCC > 3 cm). Multivariate Cox regression was used to identify predictor of extrahepatic recurrence. Results During a median follow-up of 27.0 months, the overall recurrence rate was 75.4%. Only 8.0% of patients had metastases at first recurrence (5.4% in the ≤3 cm group and 10.7% in the >3 group; p=0.002), while the overall extrahepatic recurrence rate was 26.0% (21.2% and 31.0% patients in the ≤3 cm and >3 cm groups, respectively; p=0.0006) (Figure 1). Compared to those with larger tumors, patients with HCC ≤ 3 cm had a significantly longer recurrence-free survival (12.0 [95% CI 10.7-13.3] vs. 9.7 [95% CI 8.2-11.2] months; p=0.02) and overall survival (52.5 [95% CI 45.5-59.4] vs. 34.7 [95% CI 30.7-38.7] months; p<0.0001). HCC size ≥ 3 cm, multifocality and AFP levels were independent predictors of extrahepatic recurrence. Conclusions Although the majority of patients treated with TACE do not develop extrahepatic recurrence, the incidence of early metastases (within one year) is not negligible at all (8%). The identification of the risk factors involved (HCC size, multifocality, AFP levels) may help to assess patient prognosis and to evaluate the opportunity of an adjuvant treatment, when this will be available.