Association of New and Growing Nodules With Malignancy in Follow-Up Screening for Lung Cancer: A Cohort Study

Pulmonary nodules frequently are detected on low-dose CT (LDCT) imaging screening for lung cancer, although most are benign. Nodules detected on follow-up scans may be new or may show interval growth since the baseline screening.

What is the magnitude of the risk of malignancy among new or growing nodules detected on follow-up LDCT imaging?

Participants in the LDCT imaging screening arm of the National Lung Cancer Screening Trial with a baseline screening and at least 1 follow-up screening were included. The primary exposure of interest was nodules that were new or growing on the first follow-up LDCT imaging screening (T1). Other covariates included age, sex, family history of lung cancer, presence of emphysema, nodule size, attenuation, lobe location, and spiculation. The primary outcome was lung cancer diagnosis within 2 years of T1.

Among 24,604 participants with baseline and T1 follow-up LDCT imaging, 6,952 participants showed nodules present on T1, from which lung cancer was diagnosed within 2 years in 208 participants. Compared with preexisting nodules with no growth, new nodules were associated with nearly 4-fold greater odds of a lung cancer diagnosis within 2 years (OR, 3.9; 95% CI, 2.51-6.05; P < .0001); preexisting nodules with growth were associated with nearly 20-fold increased odds (OR, 19.7; 95% CI, 13.6-28.4; P < .0001).

Our results show that new and growing nodules detected on follow-up LDCT imaging are associated strongly with the risk of malignancy. The magnitude of these risks is substantially greater than for most other well-established risk factors.