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The exclusion of pathological involvement of mediastinal lymph nodes in patients affected by NSCLC plays a central role in assessing their prognosis and operability. Ceron et al. developed a software - called M.E.S.S.i.a (Mediastinal Evaluation with Statistical Support; instan approach) - that allows the calculation of the residual probability of lymph node involvement after a certain number of tests has been done, by integrating every test result with the pre-test prevalence. M.E.S.S.i.a. bridges a gap of current American College of Chest Physicians (ACCP) guidelines, providing probability values of mediastinal metastasis for a correct clinical decision. We conducted a preliminary retrospective study in a series of 108 patients affected by non small cell lung cancer (NSCLC). Pathological staging was compared to the probability of nodal involvement calculated by M.E.S.S.i.a. software. Forty-two out of 108 subjects (39%) had a calculated post-test probability <8%; none of these had proven N2/N3 metastasis at surgical staging (negative predictive value, NPV: 100%). In 12/41 cases M.E.S.S.i.a. was able to avoid invasive procedures. The remaining 66 (61%) patients did not reach the surgical threshold; among these, 11 displayed N2 positivity at pathological staging. Receiving operator curve (ROC) analysis produced an area under curve (AUC) value of 0.773 (p<0.001). These preliminary data show high accuracy of M.E.S.S.i.a. software in excluding N2/N3 lymph node involvement in NSCLC. We have therefore promoted a prospective multicenter study in order to to get a validation of the calculator at different levels of probability of lymph node involvement. The recruitable subjects are potentially operable NSCLC patients; the gold standard for detection of mediastinal disease is the surgical lymph node dissection.