Correspondence on Rajyaguru et al
Authors: Judit Boda-Heggemann, Eleni Gkika, Nicolaus Andratschke, Oliver Blanck, Matthias Guckenberger, Frank Lohr, Thomas B. Brunner
Journal: Journal of Clinical Oncology (2018)

Oncology, Rajyaguru et al 1 report on a retrospective comparison of two local ablative methods (stereotactic body radiotherapy [SBRT] and radiofrequency ablation [RFA]) for the management of localized hepatocellular carcinoma (HCC) using the National Cancer Database.The authors find that overall survival is better in the RFA than in the SBRT cohort, even when some parameters are matched.For the comparison of effectiveness of local ablative methods, prospective randomized studies are still missing, and hence, retrospective analyses of large databases such as the study by Rajyaguru et al are relevant as the best evidence at hand.This study is specifically impressive because it reports data on almost 4,000 patients.However, although some limitations are discussed by the authors, several major limitations remain unaddressed, which we would like to highlight.First, the major weakness of the study design is that information on the liver function of patients is missing (ie, Child-Turcotte-Pugh [CTP] score, which is the predominant prognostic factor, because a majority of patients die as a result of liver failure and portal hypertension).Moreover, data on Barcelona Clinic Liver Cancer stage and presence of portal vein invasion are also missing.The authors attempt to compensate for missing CTP score by providing the Ishak fibrosis score, although this information is available for few patients (SBRT, 16%; RFA, 29%).However, the prognostic value of the Ishak score is low compared with that of CTP score, 2 and comorbidity scores also cannot compensate for missing CTP score.Finally, clinical TNM stage I and II data are assumed to represent exclusively T stage, ignoring N stage, and not to represent prognostic stage groups I or II.Therefore, the authors' matched pair analysis explores only minor prognostic variables and thus cannot achieve properly matched patient cohorts.We suspect that the difference in survival reported is a result of selection bias, mainly resulting from imbalanced CTP scores and Barcelona Clinic Liver Cancer stages.Second, this analysis excludes patients receiving any form of adjuvant or neoadjuvant therapy or other forms of local ablative therapies.This is intriguing, because the typical course of the disease almost inadvertently requires further treatment, as discussed by the authors.This exclusion raises important uncertainties about patient selection, because it does not reflect common practice.Third, regarding patient numbers, there is a major imbalance between the two treatment arms (SBRT, n 5 296 v RFA, n 5 3,684), which underlines the risk of a major selection bias.One has to assume that only patients who were not candidates for other treatment options were referred for SBRT.Interestingly, patients receiving RFA were more likely to have private insurance, and they were younger compared with patients receiving SBRT.Both of these factors would have a direct impact on survival.Fourth, much of the authors' discussion focuses on local control (LC) after RFA and SBRT, and interestingly, the authors