A comparative study of surgery versus radiation therapy on the risk of cardiovascular disease mortality in patients with early-stage non-small cell lung cancer

Objective: Non-small cell lung cancer (NSCLC) lung cancer continues to be a substantial issue in public health, and cardiovascular disease (CVD) is also an important cause of death in NSCLC patients. There is a lack of studies comparing the effects of surgery and radiation therapy on the risk of CVD-mortality in patients with early-stage NSCLC. This study planned to compare the effects of surgery alone and radiation therapy alone on the risk of CVD-mortality in patients with early-stage NSCLC. Methods: In this cohort study, the data of 32896 participants with NSCLC at stage I or stage II in 2010-2015 were retrieved from the surveillance, epidemiology, and end results (SEER) database. The primary endpoint of this study was CVD mortality, indicating patients died of CVDs and the follow-up was ended in 2020. Univariable Cox regression model was applied to identify covariates. The associations of surgery or radiation therapy with CVD-mortality in in patients with early-stage NSCLC were evaluated via univariable and multivariable Cox regression models and Fine-Gray competitive risk model. Hazards ratio (HR) and confidence interval (CI) were computed. Results: The median follow-up time was 48.00 (17.00, 60.00) months. There were 854 (6.45%) participants died of CVD in the radiation therapy group and 729 (5.35%) participants died of CVD in the surgery group. After adjusting for confounding factors, the elevated risk of CVD mortality in patients with early-stage NSCLC was observed in patients receiving radiation therapy compared to those receiving surgery (HR=2.33, 95%CI: 2.02-2.69). In the competing risk model, the risk of CVD mortality in patients with early-stage NSCLC was also increased in patients receiving radiation therapy (HR=1.37, 95%CI: 1.2.6-1.55). In the PSM group, the risk of CVD mortality in patients with early-stage NSCLC was also increased in patients who underwent radiation therapy (HR=2.62, 95%CI: 2.12-3.24). Subgroup analysis also revealed that radiation therapy was correlated with increased risk of CVD mortality in NSCLC patients with tumor size ≥50 mm or <50 mm, the original primary site in the left or right, histologic types of squamous cell NSCLC or adenocarcinoma NSCLC, stage I and II, and patients ≥ 65 years or < 65 years. Conclusions: Radiation therapy was associated with elevated risk of CVD mortality compared to surgery in patients with early-stage NSCLC.