Epidemiological characteristics and risk factors of lung cancer in a population with incidental pulmonary nodules in China: a prospective multicenter study of 10,560 cases

Background: Lung cancer incidence and mortality continue to rise in China, highlighting the need for a deeper understanding of its epidemiology and optimal screening targets. Methods: A total of 10,560 participants with 5-30 mm pulmonary nodules incidentally detected via low-dose computed tomography (LDCT)/CT were enrolled from 23 hospitals (October 2018-May 2021) and followed for 2-3 years for evaluation of circulating tumor DNA (ctDNA) biomarkers to distinguish malignant and benign nodules. Demographic, clinical, and imaging data were collected and analyzed. Lung cancer risk factors were assessed using stepwise single and multiple-factor binary logistic regression. This study reports only the baseline epidemiological characteristics of the population and the associated risk factors of lung cancer. While 97.1% of females and 37.8% of males were non-smokers, and 68.65% of participants had no occupational exposure, 71.10% had a history of second-hand smoke exposure. Most nodules were solitary (81.24%), sub-centimeter (78.22%), and non-solid (62.49%). Malignancy was identified in 17.33% of nodules, with 97.32% classified as early-stage lung adenocarcinoma (AJCC stage 0-I: 90.35%). The malignant rate increased with age and nodule size and was also associated with multiple nodules, ground-glass nodules (GGNs), upper lobe location, and female sex. Proportion of patients with malignant nodules was similar between non-high-risk (21.04%) and high-risk (17.92%) groups based on current Chinese screening guidelines, while proportions of benign nodules were notably high for solid nodules (37.21%) and small nodules (20.15%). Conclusion: Our large-scale investigation provides updated data to guide future precise clinical management of pulmonary nodules, with a particular focus on younger females and reducing overtreatment.