Characterizing Lung-RADS category 4 lesions in a university lung cancer screening program

To assess the prevalence of lung cancer in Lung-RADS category 4 patients, and to elucidate if clinical or imaging features help differentiate benign lesions from lung cancer. A retrospective review of lung cancer screening (LCS) studies at a single university screening program between January 2018 and December 2021 identified all patients with Lung-RADS category 4 lesions. Patient demographics, symptoms within the prior 6 months, and imaging features were recorded. During the defined period, 4819 baseline and annual LCS exams were performed; 7.6 % (n = 368) of exams had category 4 nodules and 59 (1.2 %) patients had biopsy-proven lung cancer. Distribution of Lung-RADS category 4 lesions and lung cancer diagnosis were as follows: 4A - 223 nodules, 6.3 % malignant; 4B - 114 nodules, 20.2 % malignant; and 4X - 31 nodules, 71.0 % malignant. Symptoms were reported in 9.0 % (n = 20) of category 4A (2 were malignant), 15.8 % (n = 18) category 4B (1 was malignant) and 22.6 % (n = 7) category 4X (5 were malignant). Imaging features associated with malignancy included endobronchial obstruction with distal atelectasis, pleural tethering, irregular shape, cavitation, and heterogeneous cystic appearance. Twenty-four nodules increased in size, however, only 7 were biopsy proven. Relative to the risk seen with 4A disease, multivariable logistic analyses showed that the odds of a malignancy increased significantly by 3.8 fold (95 % CI: 1.9, 7.9) and 39.2 fold (95 % CI: 14.9, 103.0) with 4B and 4X disease, respectively (p