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

Abstract

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 propensity-score 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.

Keywords: CoC, Commission on Cancer; NCDB, National Cancer Database; NSCLC, non–small cell lung cancer; SBRT, stereotactic body radiation therapy; instrumental variable; stage I lung cancer; stereotactic body radiation therapy.

Graphical abstract

Survival curve comparing overall survival after adjusting for the instrument.

Figure 1

Kaplan-Meier survival curve comparing overall survival between propensity-matched cohorts. Shading indicates 95% CI. SBRT, Stereotactic body radiation therapy.

Figure 2

Instrumental-variable–adjusted survival curve comparing overall survival after adjusting for the instrument. Shading indicates 95% CI.

Figure 3

Depiction of overall findings of our work. We performed an instrumental variable analysis comparing overall survival for patients with stage I non–small cell lung cancer treated with surgical resection versus stereotactic body radiation therapy (SBRT). To be valid, our instrument, facility-level SBRT utilization rate, must be correlated with the treatment of interest, but not with the outcome. In our instrumental–variable (IV)-adjusted survival analysis, both lobectomy and sublobar resection were associated with improved survival relative to SBRT. These findings have important implications regarding optimal shared decision making. NSCLC, Non-small ling cancer.