Prognostic value of CT-defined ground-glass opacity in early-stage lung adenocarcinomas: a single-center study and meta-analysis

Objectives The prognostic value of ground-glass opacity at preoperative chest CT scans in early-stage lung adenocarcinomas is a matter of debate. We aimed to clarify the existing evidence through a single-center, retrospective cohort study and to quantitatively summarize the body of literature by conducting a meta-analysis. Methods In a retrospective cohort study, patients with clinical stage I lung adenocarcinoma were identified, and the prognostic value of ground-glass opacity was analyzed using multivariable Cox regression. Commercial artificial intelligence software was adopted as the second reader for the presence of ground-glass opacity. The primary end points were freedom from recurrence (FFR) and lung cancer-specific survival (LCSS). In a meta-analysis, we systematically searched Embase and OVID-MEDLINE up to December 30, 2021, for the studies based on the eighth-edition staging system. The pooled hazard ratios (HRs) of solid nodules (i.e., absence of ground-glass opacity) for various end points were calculated with a multi-level random effects model. Results In a cohort of 612 patients, solid nodules were associated with worse outcomes for FFR (adjusted HR, 1.98; 95% CI: 1.17–3.51; p = 0.01) and LCSS (adjusted HR, 1.937; 95% CI: 1.002–4.065; p = 0.049). The artificial intelligence assessment and multiple sensitivity analyses revealed consistent results. The meta-analysis included 13 studies with 12,080 patients. The pooled HR of solid nodules was 2.13 (95% CI: 1.69–2.67; I 2 = 30.4%) for overall survival, 2.45 (95% CI: 1.52–3.95; I 2 = 0.0%) for FFR, and 2.50 (95% CI: 1.28–4.91; I 2 = 30.6%) for recurrence-free survival. Conclusions The absence of ground-glass opacity in early-stage lung adenocarcinomas is associated with worse postoperative survival. Clinical relevance statement Early-stage lung adenocarcinomas manifesting as solid nodules at preoperative chest CT, which indicates the absence of ground-glass opacity, were associated with poor postoperative survival. There is room for improvement of the clinical T categorization in the next edition staging system. Key Points • In a retrospective study of 612 patients with stage I lung adenocarcinoma, solid nodules were associated with shorter freedom from recurrence (adjusted hazard ratio [HR], 1.98; p = 0.01) and lung cancer-specific survival (adjusted HR, 1.937; p = 0.049). • Artificial intelligence-assessed solid nodules also showed worse prognosis (adjusted HR for freedom from recurrence, 1.94 [p = 0.01]; adjusted HR for lung cancer-specific survival, 1.93 [p = 0.04]). • In meta-analyses, the solid nodules were associated with shorter freedom from recurrence (HR, 2.45) and shorter overall survival (HR, 2.13).