Synchronous Primary Early-Stage Non-Small Cell Lung Cancer: Trends in Management and Factors Associated with Improved Survival.

Background: Outcomes after multi-modality curative-intent treatment for patients with synchronous primary early-stage-I non-small cell lung cancer (SPELC) are inadequately understood.

Methods: We performed a retrospective study using the Veterans Health Administration database of patients diagnosed with two stage I SPELC who received treatment with either stereotactic body radiotherapy (SBRT) and/or surgery from 2006-2024. We evaluated utilization of SBRT and surgery as well factors associated with overall survival (OS) and disease-free survival (DFS) via Cox proportional hazard models.

Results: A total of 835 patients were included: 294 (35.2%) underwent SBRT-SBRT, 149 (17.8%) received SBRT-surgery, and 392 (47%) underwent surgery-surgery. Patients treated with SBRT had more comorbidities (p<0.0001) and were older (p<0.0001). Utilization of SBRT increased from <20% in 2008 to >60% of cases in 2024. The adjusted 5-year OS was 51.7% (SBRT-SBRT) versus 72% (SBRT-Surgery), versus 66.7% (surgery-surgery) (p<0.0001). Multivariable analysis demonstrated that patients who underwent SBRT-SBRT had worse OS (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.32-2.22) but those in the SBRT-surgery group and surgery-surgery group had similar OS. Adjusted 5-year DFS was 42.7% (SBRT-SBRT) versus 42.6% (Surgery-SBRT) versus 57.26% (surgery-surgery). On multivariable analysis, DFS was inferior in the SBRT-SBRT group (HR 1.525, 1.198-1.942, p=0.0006) and SBRT-Surgery group (HR 1.530, 1.011-2.314, p=0.04) than the surgery-surgery group.

Conclusions: Among Veterans with Stage I SPELC, there is heterogeneity in outcomes based on treatment modality among other factors. Patients who are selected for surgery for both lesions have the best DFS, but similar OS to those who undergo surgery-SBRT.