Central location and risk of imaging occult mediastinal lymph node involvement in cN0T2-4 non-small cell lung cancer

Background: Appropriate pre-operative staging is a cornerstone in the treatment of non-small cell lung cancer (NSCLC). Central location and size greater than 3 cm are amongst indications for pre-operative invasive mediastinal staging but the quality of the evidence behind this recommendation is low. Methods: We retrospectively reviewed all cases of cT2-4N0M0 NSCLCL after CT and TEP-CT which underwent surgical resection with lymph node dissection or had a positive invasive pre-operative mediastinal staging in our institution from 2014 to 2018. Results: Three hundred and ten patients met inclusion criteria, 79 (25.5%) central and 231 (74.5%) peripheral tumors. Central tumor location was associated with a higher prevalence of pN2-3 disease (17.7% vs. 6.1%, P<0.001). In a multivariate analysis, central tumor location remained the only factor statistically associated with imaging occult mediastinal disease (OR 3.23, 95% CI: 1.45-7.18). NPV of PET-CT for occult mediastinal disease was 0.83 (95% CI: 0.72-0.90) in central and 0.94 (95% CI: 0.90-0.97) in peripheral tumor. Central location was also associated with a higher prevalence of occult N1 to N3 disease (43.0% vs. 15.2%, P<0.001). Conclusions: This study suggests that invasive mediastinal staging is required in central cT2-4N0 NSCLC but can be questioned in peripheral one, especially in cT2N2 subgroup if the patient is a candidate for lobar resection.