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Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the “Italian VATS-Group” database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan–Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44–2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11–2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96–0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30–0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15–3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01–1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging.

Results of the univariate analysis on the factors associated with the development of postoperative hypercapnia. (DOCX 13 kb)

Figure S1. Visual analog scale for the assessment of patient’s dyspnea. Figure S2. Mean (standard deviation) FiO2 in the two study groups (p = 0.23 for the inter-group comparison). Figure S3. Kaplan–Meier plots of the cumulative incidence of moderate-to-severe postoperative hypoxemia, which was defined as a PaO2/FiO2 ratio lower than 200 mmHg. Figure S4. Postoperative dyspnea, as assessed by the visual analog scale, in the two study groups. No inter-group differences were detected (ANOVA p = 0.97). A part of these results is displayed in Table 1. (PPTX 200 kb)