Comparative effectiveness of stereotactic body radiation therapy versus surgery for stage I lung cancer in otherwise healthy patients: An instrumental variable analysis

Objectives: Stereotactic body radiation therapy (SBRT) is an established primary treatment modality in patients with lung cancer who have multiple comorbidities and/or advanced-stage disease. However, its role in otherwise healthy patients with stage I lung cancer is unclear. In this context, we compared the effectiveness of SBRT versus surgery on overall survival using a national database. Methods: We identified all patient with clinical stage I non-small cell lung cancer from the National Cancer Database from 2004 to 2016. We defined otherwise healthy patients as those with a Charlson-Deyo comorbidity index of 0 and whose treatment plan included options for either SBRT or surgery. We further excluded patients who received SBRT due to a contraindication to surgery. We first used propensity score matching and Cox proportional hazard models to identify associations. Next, we fit 2-stage residual inclusion models using an instrumental variables approach to estimate the effects of SBRT versus surgery on long-term survival. We used the hospital SBRT utilization rate as the instrument. Results: Of 25,963 patients meeting all inclusion/exclusion criteria, 5465 (21%) were treated with SBRT. On both Cox proportional hazards modeling and propensityscore matched Kaplan-Meier analysis, surgical resection was associated with improved survival relative to SBRT. In the instrumental-variable-adjusted model, SBRT remained associated with decreased survival (hazard ratio, 2.64; P < .001). Both lobectomy (hazard ratio, 0.17) and sublobar resections (hazard ratio, 0.28) were associated with improved overall survival compared with SBRT (P < .001). Conclusions: In otherwise healthy patients with stage I NSCLC, surgical resection is associated with a survival benefit compared with SBRT. This is true for both lobar and sublobar resections. (JTCVS Open 2022;9:249-61)