• Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115.

Background: Lung-RADS version 1.1 (v1.1) classifies all solid nodules <6 mm as category 2. Lung-RADS v1.1 also classifies solid intermediate-size (6 to <10 mm) nodules as category 2 if perifissural and having triangular, polygonal, or ovoid shape (indicative of intrapulmonary lymph nodes). Additional category 2 criteria could reduce false-positive results of screening examinations. Objective: To evaluate the impact of proposed strategies to reduce false-positive results for intermediate-size nodules on lung cancer screening CT evaluated using Lung-RADS v1.1. Methods: This retrospective study entailed secondary analysis of National Lung Screening Trial (NLST) data. Of 1387 solid nodules measuring 6.0-9.5 mm on baseline screening CT examinations in NLST, all 38 nodules in patients who developed cancer, and a random sample of 200 nodules in patients who did not develop cancer, were selected for further evaluation. Cancers were required to correspond with the baseline nodule on manual review. After exclusions, the sample included 223 patients (median age, 62 years; 143 men, 53 women; 196 benign nodules, 27 malignant nodules). Two thoracic radiologists independently reviewed baseline examinations to record nodule diameter and volume using semiautomated software and classify whether nodules had perifissural location, other subpleural location, and triangular, polygonal, or ovoid shape. Different schemes for category 2 assignment were compared. Results: Across readers, Lung-RADS v1.1 had sensitivity of 89-93% and specificity of 26-31%. A modification assigning nodules <10 mm with triangular, polygonal, or ovoid shape in other subpleural locations (vs only perifissural location) as category 2 had sensitivity of 85-93% and specificity of 47-51%. Using volume cutoffs in Lung-RADS v1.1 had sensitivity of 89-93% and specificity of 37% (both readers). Both schemes' sensitivity was not significantly different from Lung-RADS v1.1 (all p>.05). Both schemes' specificity was significantly better than Lung-RADS v1.1 (all p<.05). Combining the two strategies yielded sensitivity of 85-93% and specificity of 58-59%. Conclusion: Classifying intermediate-size nodules with triangular, polygonal, or ovoid shape in any subpleural location (not just perifissural) as category 2, and use of volume- rather than diameter-based measurements, improves Lung-RADS specificity without decreased sensitivity. Clinical Impact: The findings can help reduce false-positives results, reducing 6-month follow-up examinations for benign findings.