CT-Detected Subsolid Nodules: A Predictor of Lung Cancer Development at Another Location?

SIMPLE SUMMARY: The risk assessment of pulmonary nodules on chest computed tomography (CT) is key to the early detection of lung cancer. Whereas a nodule’s morphological characteristics are strong predictors of malignancy for that individual nodule, it remains unclear whether the frequency and CT features of pulmonary nodules contribute to the prediction accuracy of future development of LC in another location. This was found by performing risk prediction modelling using age, sex, and CT measures from lung-cancer-free scans as predictors. We found that a greater number of part-solid and ground-glass nodules in the earliest scan was linearly associated with a higher risk of lung cancer developing in another location in the future. There were also indications that CT biomarkers of other pulmonary and heart diseases are risk factors for lung cancer. Our findings endorse the utilization of information from the entire scan to improve the accuracy of lung risk assessment. ABSTRACT: The purpose of this case–cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.