Long-Term Follow-up of Small Pulmonary Ground-Glass Nodules Stable for 3 Years: Implications of the Proper Follow-up Period and Risk Factors for Subsequent Growth

How long persistent and stable ground-glass nodules (GGNs) should be followed is uncertain, although a minimum of 3 years is suggested. Here, we evaluated a group of GGNs that had remained stable for an initial period of 3 years with the aim of determining the proportion of GGNs showing subsequent growth after the initial 3 years and identifying the clinical and radiologic factors associated with subsequent growth. We retrospectively analyzed patients who underwent further computed tomography (CT) after the initial 3-year follow-up period showing a persistent and stable GGN (at least 5 years of follow-up from the initial CT). Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of the 218 patients, 14 had 15 GGNs showing subsequent growth after the initial 3 years during the median follow-up period of 6.4 years. For the person-based analysis, the frequency of subsequent growth of GGNs that had been stable during the initial 3 years was 6.7% (14 of 218). For the nodule-based analysis, the frequency was 3.3% (15 of 453). In a multivariate analysis, age 65 years or older (OR = 5.51, p = 0.012), history of lung cancer (OR = 6.44, p = 0.006), initial size 8 mm or larger (OR = 5.74, p = 0.008), presence of a solid component (OR = 16.58, p = 0.009), and air bronchogram (OR = 5.83, p = 0.015) were independent risk factors for subsequent GGN growth. For the individuals with GGNs having the aforementioned risk factors, the longer follow-up period is required to confirm subsequent GGN growth.