The Growth of Screening-Detected Pure Ground-Glass Nodules Following 10 Years of Stability

Background: It remains uncertain for how long pure ground-glass nodules (pGGNs) detected on low-dose CT (LDCT) imaging should be followed up. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. Research Question: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? Study Design and Methods: This was a retrospective cohort study originating from participants with pGGNs detected on LDCT scans between 1997 and 2006 whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study participants were followed up per our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by ≥ 2 mm or the appearance of new solid portions within the nodules. Results: A total of 89 patients with 135 pGGNs were followed up for a median of 193 months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a size change was 71 months. Of the 135 pGGNs, 122 were detected on the first LDCT scan and 13 were newly detected on the follow-up CT scan. An increase in size was observed within 5 years in 8 nodules (34.8%), between 5 and 10 years in 12 nodules (52.2%), and after 10 years in three nodules (13.0%). Fifteen nodules were histologically confirmed as adenocarcinoma by surgery. Among the 76 pGGNs stable for 10 years, 3 (3.9%) increased in size. Interpretation: Among pGGNs that remained stable for 10 years, 3.9% eventually grew, indicating that some pGGNs can grow even following a long period of stability. We suggest that pGGNs may need to be followed up for > 10 years to confirm growth.