Associations between CT characteristics of lung cancer lesions and histologic subtypes in lung cancer screening

Abstract Objectives To assess the associations between imaging characteristics and histologic subtype in screen-detected lung cancers. Materials and methods We retrospectively analyzed histologically confirmed lung cancers from the NELSON trial. Radiological features (location, margins, nodule type, size, volume, volume doubling time (VDT), pleural distance) were annotated using standardized protocols. Logistic regression adjusted for age, sex, smoking, and stage assessed associations with adenocarcinoma (ADC) versus non-ADC. Sensitivity analyses included models with VDT and were restricted to stage I–II disease. Results Among 213 cancers, 67.5% were ADC and 32.5% non-ADC. Participants were predominantly male (82.4%), with a mean age of 64 years; 73.7% had stage I–II disease. ADCs were more often early stage (86.1% vs 47.8%), smaller (14.6 vs 17.3 mm), and more frequently located in the right upper lobe (49.3% vs 31.9%). In multivariable analysis, larger lesion size was associated with lower odds of ADC (odds ratio (OR) = 0.92, 95% CI 0.85–0.99), while pleural attachment increased the odds (OR = 6.67, 95% CI 1.20–33.33). Compared with the right upper lobe, lesions in the left lower (OR = 0.28), right lower (OR = 0.24), and right middle lobes (OR = 0.17) had lower odds. Model discrimination was acceptable (Area under the curve (AUC) = 0.75), with sensitivity 96% and specificity 29%. In sensitivity analyses, higher VDT was associated with ADC (OR = 5.65), with consistent findings in stage I–II disease. Conclusion In low-dose computed tomography screening, ADCs are smaller, slower-growing, and more often upper-lobe or pleural-based. These patterns may support improved diagnostic interpretation and personalized nodule management. Key Points Question Radiological features guide malignancy risk, but their association with histologic subtype in screen-detected lung cancers remains unclear, limiting subtype-specific diagnostic interpretation. Findings Compared to non-adenocarcinomas, adenocarcinomas were smaller, more often pleural-based, and predominantly located in upper lobes, while lower and middle lobe lesions showed lower odds. Clinical relevance Recognizing imaging patterns associated with histologic subtype may improve understanding of tumor biology and inform future multimodal diagnostic approaches.