ABSTRACT
CONTEXT: Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) therapy has been used for patients with large hepatocellular carcinoma tumors, but the survival benefits of combined treatment are not known. OBJECTIVE: To compare rates of survival of patients with large hepatocellular carcinoma tumors who received treatment with TACE combined with RFA therapy (TACE-RFA), TACE alone, and RFA alone. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial conducted from January 2001 to May 2004 among 291 consecutive patients with hepatocellular carcinoma larger than 3 cm at a single center in China. INTERVENTION: Patients were randomly assigned to treatment with combined TACE-RFA (n = 96), TACE alone (n = 95), or RFA alone (n = 100). MAIN OUTCOME MEASURES: The primary end point was survival and the secondary end point was objective response rate. RESULTS: During a median 28.5 months of follow-up, median survival times were 24 months in the TACE group (3.4 courses), 22 months in the RFA group (3.6 courses), and 37 months in the TACE-RFA group (4.4 courses). Patients treated with TACE-RFA had better overall survival than those treated with TACE alone (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.33-2.63; P < .001) or RFA (HR, 1.88; 95% CI, 1.34-2.65; P < .001). In a preplanned substratification analysis, survival was also better in the TACE-RFA group than in the RFA group for patients with uninodular hepatocellular carcinoma (HR, 2.50; 95% CI, 1.42-4.42; P = .001) and in the TACE-RFA group than the TACE group for patients with multinodular hepatocellular carcinoma (HR, 1.99; 95% CI, 1.31-3.00; P < .001). The rate of objective response sustained for at least 6 months was higher in the TACE-RFA group (54%) than with either TACE (35%; rate difference, 0.19; 95% CI, 0.06-0.33; P = .009) or RFA (36%; rate difference, 0.18; 95% CI, 0.05-0.32; P = .01) treatment alone. CONCLUSION: In this patient group, TACE-RFA was superior to TACE alone or RFA alone in improving survival for patients with hepatocellular carcinoma larger than 3 cm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00479050.
