Huo and colleagues 1 appropriately note that the low complete response rate to radiofrequency ablation (RFA) in our study contrasts markedly with much of the published literature. Their surprise regarding this finding originates from the commonly held belief that RFA effectively ablates hepatocellular carcinoma. While it is possible that a steep learning curve for RFA may have contributed to the heterogeneity of ablation in our study, it is important to recognize that the medical community's faith in the success of radiofrequency ablation is not supported by pathologic tumor response data. In fact, the papers cited by Huo and colleagues provide excellent examples of the literature that has supported the concept that RFA is a "curative" treatment, without pathologic proof. What should be noted is that these papers do not correlate radiographic tumor response with actual pathologic tumor destruction, and none of these papers provide histologic tumor response data as rigorous as our explant evaluation.
We do agree with Huo and colleagues that our provocative finding of inferior outcomes in complete responders may be the result of selection bias in our retrospective study, as patients with radiographically advanced or sinister tumors may have received more aggressive and complete locoregional therapy. Selection bias in all of its forms cannot be controlled in any retrospective study, and our paradoxical data indeed suggest that a randomized, prospective trial is required to resolve these issues. It is unfortunate that such a trial is unlikely to be performed, however, and we must therefore rely on imperfect but available retrospective data to guide our decision making with respect to pretransplant neoadjuvant therapy. We also suggest that the main benefit of pretransplant locoregional therapy may be the ability to control tumor growth, or even downstage tumors, while awaiting transplantation, rather than hoping to improve posttransplant outcome. We eagerly await the publication of additional data regarding this topic to help clarify whether invasive locoregional therapies benefit, harm, or have no effect on transplant recipient outcomes.