Stereotactic ablative radiotherapy versus video-assisted lobectomy for operable stage I non-small-cell lung cancer: study protocol for an emulated target trial.

[INTRODUCTION] Video-assisted thoracoscopic surgery (VATS) lobectomy is a commonly employed surgical technique for the management of operable early stage non-small cell lung cancer (NSCLC). This procedure, however, is dependent on the patient's ability to tolerate surgery. In light of this, stereotactic ablative radiotherapy (SABR) has emerged as a viable alternative treatment strategy for patients who are inoperable or who refuse surgery. Considering the lack of randomised controlled trials and the increased risk of bias in observational cohort studies, this study protocol proposes an emulated target trial design to investigate the causal effect of SABR, in comparison to VATS, on overall survival in operable early stage NSCLC patients.

[METHODS AND ANALYSIS] Data on NSCLC patients will be collected from routinely collected university hospital records linked with German cancer registry data. This study protocol was developed using the target trial methodology outlined by Hernan . The protocol establishes specific parameters for key trial components in order to mitigate bias in the analysis of observational data and to facilitate the calculation of causal estimands. The target trial design that would be emulated is a multicentre open-label two-parallel arm superiority randomised trial. Mediators and confounding variables were determined through the use of a directed acyclic graph. The statistical analysis aims to measure the per-protocol and intention to treat effect of SABR versus VATS within 3 months of diagnosis, on survival, through the difference in restricted mean survival times, using weighted non-parametric Kaplan-Meier curves.

[ETHICS AND DISSEMINATION] The Ethics Committee of the Medical Faculty of Martin Luther University Halle-Wittenberg with an approved addendum with Dnr 2023-112 has approved this study. The study uses anonymised routinely collected hospital and cancer registry data in accordance with applicable data protection regulations. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.