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

Abstract

Objectives: 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.

Materials/methods: 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.

Results: 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 < 0.0001). A separate analysis involving only category 4A and 4B patients jointly showed that disease category (OR = 3.0; 95 % CI: 1.5, 6.4) and additional imaging features (OR = 3.2; 95 % CI: 1.4, 7.0) were significant predictors of malignancy. The presence of clinical symptoms was not statistically associated with lung cancer.

Conclusions: Lung-RADS 4 nodules were found in 7.6% of LCS examinations and 16% of these nodules were lung cancer. The probability of lung cancer increases from category 4A to 4X, and imaging features may help differentiate benign from malignant nodules in this LCS category.

Keywords: Category 4 nodule; Lung cancer; Lung cancer screening; low dose CT; lung-RADS.