Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial
Authors: Bousema Jelle E. , Dijkgraaf Marcel G.W. , van der Heijden Erik H.F.M. , Verhagen Ad F.T.M. , Annema Jouke T. , van den Broek Frank J.C. , Papen-Botterhuis Nicole E. , Youssef-El Soud Maggy , van Boven Wim J. , Daniels Johannes M.A. , Heineman David J. , Zandbergen Harmen R. , Brocken Pepijn , Horn Thirza , Steup Willem H. , Braun Jerry , Ramai Rajen S.R.S. , Beck Naomi , Hoeijmakers Fieke , Barlo Nicole P. , van Dorp Martijn , Schreurs W. Hermien , Dingemans Anne-Marie C. , Sprooten Roy T.M. , Maessen Jos G. , Claessens Niels J.M. , Lardenoije Jan-Willem H.P. , Hiddinga Birgitta I. , Van De Wauwer Caroline , van der Wekken Anthonie J. , Hanselaar Wessel E. , ThJ Kortekaas Robert , Bard Martin P. , Rijna Herman , Bootsma Gerben P. , Vissers Yvonne L.J. , Veen Eelco J. , van der Leest Cor H. , Citgez Emanuel , van Duyn Eino B. , Marres Geertruid M.H. , van Thiel Eric R. , van Schil Paul E. , van Meerbeeck Jan P. , Wener Reinier , Smakman Niels , van der Meer Femke , Saboerali Mohammed D. , Bosch Anne Marie , de Jong Wouter K. , van Rossem Charles C. , Lie W. Johan , Kouwenhoven Ewout A. , Staal-van den Brekel A. Jeske , Hanneman Nike M. , Heller-Baan Roxane , Noyez Valentin J.J.M. 
Published: April 2023

PURPOSE Resectable non–small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking. METHODS Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior < .0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality. RESULTS Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior = .0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first ( P = .4940). CONCLUSION On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.