Long-term surveillance of ground-glass nodules: Evidence from the MILD trial

Introduction: The purpose of this study was to evaluate the natural evolution of ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD) trial, which adopted a nonsurgical approach to this subset of lesions. Methods: From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs were identified from 1866 individuals who underwent baseline low-dose computed tomography. The features of GGNs were assessed and compared with the corresponding repeat low-dose computed tomographies after a mean time of 50.26 ± 7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs. The average of the maximum and the minimum diameters for both pGGNs and psGGNs and the maximum diameter of the solid portion of psGGNs were manually measured. At follow-up, GGNs were classified as follows: resolved, decreased, stable, or progressed (according to three defined growth patterns). Results: A total of 15 of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%) remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid component larger than 5 mm remained stable, and the other decreased in size. Four lung cancers were detected among the GGN subjects, but only one arose from a psGGN, and was resected in stage Ia. Conclusions: The progression rate of the GGNs toward clinically relevant disease was extremely low in the MILD trial and supports an active surveillance attitude.