Cancer Risk in Subsolid Nodules in the National Lung Screening Trial

Abstract

Background Subsolid pulmonary nodules, comprising pure ground-glass nodules (GGNs) and part-solid nodules (PSNs), have a high risk of indolent malignancy. Lung Imaging Reporting and Data System (Lung-RADS) nodule management guidelines are based on expert opinion and lack independent validation. Purpose To evaluate Lung-RADS estimates of the malignancy rates of subsolid nodules, using nodules from the National Lung Screening Trial (NLST), and to compare Lung-RADS to the NELSON trial classification as well as the Brock University calculator. Materials and Methods Subsets of GGNs and PSNs were selected from the NLST for this retrospective study. A thoracic radiologist reviewed the baseline and follow-up CT images, confirmed that they were true subsolid nodules, and measured the nodules. The primary outcome for each nodule was the development of malignancy within the follow-up period (median, 6.5 years). Nodules were stratified according to Lung-RADS, NELSON trial criteria, and the Brock model. For analyses, nodule subsets were weighted on the basis of frequency in the NLST data set. Nodule stratification models were tested by using receiver operating characteristic curves. Results A total of 622 nodules were evaluated, of which 434 nodules were subsolid. At baseline, 304 nodules were classified as Lung-RADS category 2, with a malignancy rate of 3%, which is greater than the 1% in Lung-RADS (P = .004). The malignancy rate for GGNs smaller than 10 mm (two of 129, 1.3%) was smaller than that for GGNs measuring 10-19 mm (11 of 153, 6%) (P = .01). The malignancy rate for Lung-RADS category 3 was 14% (13 of 67), which is greater than the reported 2% in Lung-RADS (P < .001). The Brock model predicted malignancy better than Lung-RADS and the NELSON trial scheme (area under the receiver operating characteristic curve = 0.78, 0.70, and 0.67, respectively; P = .02 for Brock model vs NELSON trial scheme). Conclusion Subsolid nodules classified as Lung Imaging Reporting and Data System (Lung-RADS) categories 2 and 3 have a higher risk of malignancy than reported. The Brock risk calculator performed better than measurement-based classification schemes such as Lung-RADS. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kauczor and von Stackelberg in this issue.

Graphical abstract

Figure 1:

Flowchart of the study shows the total number of nodules in the National Lung Screening Trial (NLST) CT arm and how many patients were excluded for this analysis. f/u = follow-up, GGN = ground-glass nodule, PSN = part-solid nodule.

Figure 2:

CT scan in 60-year-old man undergoing low-dose lung cancer screening. Scan shows a 6-mm solid polygonal nodule along the right minor fissure described as “mixed” in National Lung Screening Trial annotations. This nodule was stable over 2 years of follow-up and most likely represents an intrapulmonary lymph node.

Figure 3a:

CT scans in a 57-year-old man undergoing low-dose lung cancer screening. (a) Baseline scan shows a right upper lobe pure ground-glass nodule measuring 11 mm (arrow). Nodule was classified as Lung-RADS category 2. (b, c) CT scans obtained at second annual follow-up show that this nodule grew to 15 mm and developed a 3-mm solid component (arrows). Malignancy was subsequently diagnosed.

Figure 3b:

CT scans in a 57-year-old man undergoing low-dose lung cancer screening. (a) Baseline scan shows a right upper lobe pure ground-glass nodule measuring 11 mm (arrow). Nodule was classified as Lung-RADS category 2. (b, c) CT scans obtained at second annual follow-up show that this nodule grew to 15 mm and developed a 3-mm solid component (arrows). Malignancy was subsequently diagnosed.

Figure 3c:

CT scans in a 57-year-old man undergoing low-dose lung cancer screening. (a) Baseline scan shows a right upper lobe pure ground-glass nodule measuring 11 mm (arrow). Nodule was classified as Lung-RADS category 2. (b, c) CT scans obtained at second annual follow-up show that this nodule grew to 15 mm and developed a 3-mm solid component (arrows). Malignancy was subsequently diagnosed.

Figure 4a:

CT scans in a 60-year-old woman undergoing low-dose lung cancer screening CT. (a) Baseline scan shows a right lower lobe part-solid nodule measuring 11 mm with 5-mm solid component (arrows). Nodule was classified as Lung-RADS category 3. (b) Scan obtained at second annual follow-up shows that nodule grew to 17 mm with 7 mm solid component (arrows). Malignancy was subsequently diagnosed.

Figure 4b:

CT scans in a 60-year-old woman undergoing low-dose lung cancer screening CT. (a) Baseline scan shows a right lower lobe part-solid nodule measuring 11 mm with 5-mm solid component (arrows). Nodule was classified as Lung-RADS category 3. (b) Scan obtained at second annual follow-up shows that nodule grew to 17 mm with 7 mm solid component (arrows). Malignancy was subsequently diagnosed.