Deeper into the Mediastinum: Topographical Distribution and Histological Patterns of Occult Pn2 Disease in NSCLC Patients

Backround: The aim of the study is to assess the incidence and predictor factors of occult N2 mediastinal lymph node involvement in NSCLC patients with negative FDG uptake PET-CT. Methods: We completed a retrospective review of patient9s data with NSCLC from 2010- 2019, who had no 18FDG uptake on PET-CT and underwent anatomical surgical resection with curative intent. Multivariate statistical analysis was performed to evaluate any association between pathological variables and occult N2 involvement. No invasive mediastinal staging was carried out in the study population. Results: The pN2 incidence was 8.9% (n=89). The majority of patients were older than 57 years [ avg. 61(16±30)]. Notably, there was a 4-fold male predominance (83%), while the most frequent histological type in both sexes was adenocarcinoma (53%). In univariate analysis, lesions of left upper lobe [LUL (39%)] and right upper lobe [RUL (32%)] were significant predictors of occult N2 disease (p=0.041 vs. p=0.048). Patients with poorly differentiated carcinoma (solid/micropapillary predominant type) had an 67% elevated risk of unforeseen N2 disease (Hazard Ratio 1.71, p=0.032), while location of the tumor (central vs peripheral), didn’t positively affect nodal involvement (p=0.28). Conclusions: Our results suggest that invasive mediastinal staging should be probably encouraged in NSLCL male patients, with poorly differentiated adenocarcinoma lesions of the upper lobes. Considering the current lack of well-designed randomized trials, further studies are warranted in order to validate these findings, thus eliminating occult N2 involvement that may influence treatment decision-making and survival.