Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database

Abstract

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.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery

“…In our series, in the group without invasive testing the unexpected N2 was 9.6% while in the group with invasive testing with a 13.8% of unexpected N2, a half of them were discovered prior to surgery. These rates are similar to that in the Danish Registry (7.8%) with stage I and the Italian Registry (8.5%) with cN0 patients and tumour sizes >3 cm ( 17 , 19 ). Rates of unexpected pN2 tend to vary, ranging between 5% and 15% in the series published, and above all depend on patient selection ( 11 - 13 , 17 , 19 - 23 ).…”

“…These rates are similar to that in the Danish Registry (7.8%) with stage I and the Italian Registry (8.5%) with cN0 patients and tumour sizes >3 cm ( 17 , 19 ). Rates of unexpected pN2 tend to vary, ranging between 5% and 15% in the series published, and above all depend on patient selection ( 11 - 13 , 17 , 19 - 23 ).…”

“…In our study, we observed a significant difference in the rate of pN2 associated with cN1: 16.8% vs. 7.3% in patients with cN0. Nonetheless, there are other factors, such as histological type and SUVmax on PET, that have been shown to influence unexpected pN2 and should be taken into account ( 8 , 19 , 20 ). In a recent study based on the same GEVATS database, SUVmax on PET was an independent risk factor for unexpected lymph node involvement ( 27 ).…”

“…Despite the numerous articles on risk factors for unexpected pN2 ( 7 , 9 , 12 , 15 , 19 , 21 , 23 , 24 ), there is a paucity of evidence concerning the consequences in terms of survival when clinical mediastinal staging is less exhaustive or guidelines are not followed ( 13 , 16 ). Thornblade et al showed great variability in mediastinal staging between centres but did not provide data on long-term outcomes ( 16 ).…”