Chemoembolization for intermediate HCC: is there proof of survival benefit?

BACKGROUND: Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation(TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.
OBJECTIVES: To assess the beneficial and harmful effects of TACE or TAE. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Cancer Network register,The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Latin American Caribbean Health Sciences Literature(LILACS) from dates of inceptions up to September 2010. SELECTION CRITERIA: We considered for inclusion all randomised trials that compared TACE or TAE versus placebo, sham, or no intervention.Co-interventions were allowed if comparable between intervention groups. Trials with inadequate randomisation were excluded. DATA COLLECTION AND ANALYSIS: For all-cause mortality, we calculated the log hazard ratio (HR) with standard error as point estimate and pooled them for meta-analysis using the inverse variance method. Sub-group analyses were performed regarding intervention regimen, trial truncation, or co-interventions. We validated the results with trial sequential analyses. We used random-effects model in all meta-analyses in anticipation of statistical heterogeneity among the trials. MAIN
RESULTS: We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven trials had low risk of selection bias based on adequate generation of allocation sequence and concealment – but all these trials had other risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality,statistical heterogeneity between trials was low to moderate(I2) = 30%). Meta-analysis of trials with low risk of selection bias showed that TACE or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71–1.10). Two trials with low risk of selection bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival(hazard ratio 1.22, 95% confidence interval 0.82–1.83; P = 0.33). Trials equential analysis confirmed the absence of evidence for a beneficial effect of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. One trial investigated quality of life but did not detect any significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious complications were reported. AUTHORS’
CONCLUSIONS: There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-protected trials are needed.