Predicting the Invasiveness of Pulmonary Adenocarcinomas in Pure Ground-Glass Nodules Using the Nodule Diameter: A Systematic Review, Meta-Analysis, and Validation in an Independent Cohort

Abstract

The nodule diameter was commonly used to predict the invasiveness of pulmonary adenocarcinomas in pure ground-glass nodules (pGGNs). However, the diagnostic performance and optimal cut-off values were inconsistent. We conducted a meta-analysis to evaluate the diagnostic performance of the nodule diameter for predicting the invasiveness of pulmonary adenocarcinomas in pGGNs and validated the cut-off value of the diameter in an independent cohort. Relevant studies were searched through PubMed, MEDLINE, Embase, and the Cochrane Library, from inception until December 2022. The inclusion criteria comprised studies that evaluated the diagnostic accuracy of the nodule diameter to differentiate invasive adenocarcinomas (IAs) from non-invasive adenocarcinomas (non-IAs) in pGGNs. A bivariate mixed-effects regression model was used to obtain the diagnostic performance. Meta-regression analysis was performed to explore the heterogeneity. An independent sample of 220 pGGNs (82 IAs and 128 non-IAs) was enrolled as the validation cohort to evaluate the performance of the cut-off values. This meta-analysis finally included 16 studies and 2564 pGGNs (761 IAs and 1803 non-IAs). The pooled area under the curve, the sensitivity, and the specificity were 0.85 (95% confidence interval (CI), 0.82-0.88), 0.82 (95% CI, 0.78-0.86), and 0.73 (95% CI, 0.67-0.78). The diagnostic performance was affected by the measure of the diameter, the reconstruction matrix, and patient selection bias. Using the prespecified cut-off value of 10.4 mm for the mean diameter and 13.2 mm for the maximal diameter, the mean diameter showed higher sensitivity than the maximal diameter in the validation cohort (0.85 vs. 0.72, p < 0.01), while there was no significant difference in specificity (0.83 vs. 0.86, p = 0.13). The nodule diameter had adequate diagnostic performance in differentiating IAs from non-IAs in pGGNs and could be replicated in a validation cohort. The mean diameter with a cut-off value of 10.4 mm was recommended.

Keywords: computed tomography; diameter; invasive adenocarcinoma; meta-analysis; pure ground-glass nodule.

Figure 1

The flowchart of literature search and study selection. AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; mGGNs: mixed ground-glass nodules.

Figure 2

Forest plots on the sensitivity and specificity of the nodule size in predicting the invasiveness of pulmonary adenocarcinomas in pure ground-glass nodules. [20,22,23,29,30,31,32,33,34,40,44,45,46,47,48,49]. CI: confidence interval.

Figure 3

The summary receiver operating characteristic curve (SROC) plot on the diagnostic performance of the nodule size in predicting the invasiveness of pulmonary adenocarcinomas in pure ground-glass nodules.