To characterize the comparative effectiveness and harms of various local hepatic therapies for patients with unresectable primary hepatocellular carcinoma (HCC) who are not candidates for surgical resection or liver transplantation. Local hepatic therapies include those related to ablation, embolization, and radiotherapy.
We searched MEDLINE® and Embase® from January 2000 to July 2012. We also searched for gray literature in databases with regulatory information, clinical trial registries, abstracts and conference papers, as well as information from manufacturers.
We sought studies reporting two final health outcomes—overall survival and quality of life—and various adverse events related to the different interventions. Data were dually abstracted by a team of four reviewers. A third reviewer resolved conflicts when necessary. We assessed the quality of individual studies and graded the strength of the body of evidence according to prespecified methods.
We identified 1,707 articles through the literature search, excluded 1,665 at various stages of screening, and included 42 articles. To these we added 6 hand-searched articles for a total of 48 articles included in this review. Our searches of gray literature sources did not yield any additional published studies. The included literature was comprised of 6 randomized controlled trials (RCTs), 4 nonrandomized comparative studies, 35 case series, and 3 case reports. One RCT was rated as good, three were rated as fair, and two were rated as poor quality. We included 13 local hepatic therapies in this review; however, there was sufficient comparative evidence (three RCTs) to assess only one direct comparison: radiofrequency ablation (RFA) versus percutaneous ethanol injection (PEI)/percutaneous acetic acid injection (PAI). Three-year survival when treated with RFA was superior to that for PEI/PAI for unresectable HCC, with a moderate grade of evidence. Time to progression (TTP) and local recurrence were better for RFA than PEI/PAI, but length of stay (LOS) was longer after RFA than PEI/PAI. Strength of evidence for all other comparisons was rated insufficient. There was a low level of evidence to support longer overall survival following RFA than PEI/PAI for the subgroup of patients with larger lesion size.
Of the 13 interventions included in this report, only 1 comparison had sufficient evidence to receive a rating above insufficient. There was moderate strength of evidence demonstrating better overall survival at 3 years, a low level of evidence supporting improved overall survival for patients with larger lesion sizes, and low strength of evidence for improved TTP and local control for RFA than PEI/PAI for the treatment of unresectable HCC. A low level of evidence also supports a longer LOS following RFA than PEI/PAI. For all other outcomes and comparisons, there is insufficient evidence to permit conclusions on the comparative effectiveness of local hepatic therapies for unresectable HCC. Additional RCTs are necessary for all comparisons. Focusing on comparisons with RFA may allow for the greatest integration of new data with the current body of evidence.