Definitions of Central Tumors in Radiologically Node-Negative, Early-Stage Lung Cancer for Preoperative Mediastinal Lymph Node Staging

Background Definitions for central lung cancer have been ambiguous in guidelines, causing difficulty in selecting candidates for invasive mediastinal staging among patients with radiologically node-negative, early-stage lung cancer. Research Question What is the optimal definition for central lung cancer, which is robust to inter-reader and institutional variation, to select candidates for invasive mediastinal staging among those with clinical T1N0M0 lung cancer? Study Design and Methods Two retrospective cohorts were evaluated for the associations of central lung cancer according to 13 definitions based on chest CT with occult nodal metastasis. Univariable and multivariable ordinal logistic regression analyses were performed with the pathological N category as an ordinal outcome. Robust definitions, which retained statistical significance across multi-reader, dual-institutional datasets, were identified. For these definitions, binary diagnostic performance and inter-reader agreement were investigated. Results In the two cohorts, 807 patients (median age, 63 years; interquartile range, 56-71 years; 410 women; 33 pN1, 48 pN2, and 1 pN3) and 510 patients (median age, 65 years; interquartile range, 58-71 years; 267 women; 33 pN1, 20 pN2, and no pN3) were included, respectively. Three definitions robust to inter-reader variation and dataset heterogeneity were identified: definition 7 (concentric lines arising from the midline, inner one-third, medial margin; adjusted odds ratio [OR], 2.01; 95% confidence interval [CI], 1.13-3.51; P=0.02), definition 10 (location index-based inner one-third, center; adjusted OR, 3.60; 95% CI, 1.49-8.25; P=0.003), and definition 12 (location index-based inner one-third, medial margin; adjusted OR, 3.57; 95% CI, 1.91-6.52; P Interpretation Three definitions exhibited robust associations with occult nodal metastasis. However, selecting candidates for invasive mediastinal staging solely based on a central tumor location would be suboptimal.