Stereotactic Ablative Radiotherapy versus Video-Assisted Lobectomy for Operable Stage I Non-small-cell Lung Cancer: Study Protocol for an Emulated Target Trial

Abstract Background: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 upon 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 randomized 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:Data on NSCLC patients will be collected from German cancer registry data linked with university hospital records. This study protocol was developed using the target trial methodology outlined by Hernan et al. 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 multicenter open-label two-parallel arm superiority randomized 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 three months of diagnosis, on survival, through the difference in restricted mean survival times, using weighted nonparametric Kaplan-Meier curves. Discussion:By using retrospective data and emulating RCT principles, our study aims to overcome limitations of previous research and provide more reliable insights into the effectiveness of SABR versus VATS.