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Defining the role of radiofrequency ablation and stereotactic ablative radiotherapy in patients with high‐risk, early‐stage non‐small cell lung cancer

We read with interest the report by Dupuy et al describing 2-year outcomes in patients with medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC) who were treated with computed tomography-guided radiofrequency ablation (RFA). Their data add to the growing body of evidence demonstrating a low incidence of regional disease recurrence in patients with ES-NSCLC after local ablative therapy without any invasive lymph node staging procedures. It is questionable, however, whether their data support the overarching suggestion that RFA is a reasonable first-line alternative to stereotactic ablative radiotherapy (SABR) for patients with medically inoperable ES-NSCLC. The authors argue that the 2-year overall survival (OS) between RFA and SABR is similar, “even in an older and sicker [RFA] cohort.” Although competing risks have a clear impact on survival in these high-risk patients, details regarding comorbidities were lacking. The importance of comorbidity in any survival comparison with historical SABR data is highlighted by the example of a 2-year actuarial OS rate of 100% noted among in potentially operable patients from 2 randomized trials who were undergoing lung SABR. A purported benefit of RFA over SABR is the preservation of lung function, and the authors cite the Radiation Therapy Oncology Group 0236 trial as reporting a 12% reduction in the diffusing capacity for carbon monoxide after SABR. We would like to point out that the article cited by Dupuy et al did not report any analysis of pulmonary function. In fact, a subsequent report on the Radiation Therapy Oncology Group 0236 trial noted a nonsignificant decline in the diffusing capacity for carbon monoxide of 6% at 2 years. The authors argue that local recurrence rates of 40% were acceptable in their study because of the ability to salvage failures with either SABR or repeat RFA, and because local failures did not appear to impact on OS. This finding needs to be considered within the context of the study’s small sample size and risk of making a type II error (ie, failure to reject a false null hypothesis). It would be particularly enlightening if the authors had provided the number of patients at risk in the Kaplan-Meier analyses. Nonetheless, any perceived acceptability of local recurrence rates should be tempered by the psychological impact of recurrent disease, as well as the morbidity and resource implications of salvage treatments. We concur with the editorial accompanying the article that the high local recurrence rates after RFA decrease enthusiasm for its use as a first-line option for high-risk patients who are also eligible for SABR or surgery. RFA may have a role in previously irradiated, frail patients, although determining the efficacy of RFA versus best supportive care in a clinical trial would be challenging. Modeling studies can be helpful in such situations; for example, we previously constructed a Markov model to simulate quality-adjusted life years in extremely comorbid patients with ES-NSCLC who were receiving either SABR or best supportive care. Combining such data with robust cost information, which can differ greatly from reimbursement rates, is crucial to inform costeffectiveness in the era of increasing awareness of the financial burdens associated with cancer treatment.