Transarterial Chemoembolization in Combination with Local Therapies for Hepatocellular Carcinoma: A Meta-Analysis

Background: In previous randomized trials, transarterial chemoembolization (TACE) has shown an improvement of survival rate in hepatocellular carcinoma (HCC) when combined with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT), three-dimensional conformal radiation therapy (3D-CRT) or High-Intensity Focused Ultrasound (HIFU). Methods: Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies. Results: 10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs). Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR)(1-)year=1.10, 95% CI=0.99-1.22, p=0.073; (RR)(3-)year=2.32, 95% CI=1.52-3.53, p<0.001), TACE+RT ((RR)(1-)year=1.37, 95% CI=1.11-1.70, p=0.004; (RR)(3-)year=2.32, 95% CI=1.44-3.75, p=0.001) were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR)(1-)year=1.22, 95% CI=1.06-1.41, p=0.005; (RR)(3-)year=2.05, 95% CI=1.48-2.84, p<0.001) and TACE plus HIFU ((RR)(1-)year=1.16, 95% CI=1.01-1.33, p=0.033; (RR)(3-)year=1.66, 95%CI=1.12-2.45, p=0.011) have introduced marked survival benefit when pooling results from observational studies. Conclusions: This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.