Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial
Jelle E. Bousema, Marcel G. W. Dijkgraaf, Erik H.F.M. van der Heijden, Ad F. T. M. Verhagen, Jouke T. Annema, Frank J.C. van den Broek, Nicole E. Papen‐Botterhuis, Maggy Youssef-El Soud, Wim Jan van Boven, Johannes M. A. Daniels, David J. Heineman, H. Reinier Zandbergen, Pepijn Brocken, Thirza Horn, Willem H. Steup, Jerry Braun, Rajen Ramai, Naomi Beck, Fieke Hoeijmakers, Nicole P. Barlo, Martijn van Dorp, W. Hermien Schreurs, Anne‐Marie C. Dingemans, Roy T.M. Sprooten, Jos G. Maessen, Niels Claessens, Jan-Willem H.P. Lardenoije, Birgitta I. Hiddinga, Caroline Van De Wauwer, Anthonie J. van der Wekken, Wessel Hanselaar, Robert ThJ Kortekaas, Martin Bard, Herman Rijna, Gerben Bootsma, Yvonne L. J. Vissers, Eelco J. Veen, Cor H. van der Leest, Emanuel Citgez, Eino B. van Duyn, Geertruid M H Marres, Eric R. van Thiel, Paul Van Schil, Jan P. van Meerbeeck, Reinier Wener, Niels Smakman, Femke van der Meer, Mohammed D. Saboerali, Anne Marie Bosch, Wouter K. de Jong, Charles C. van Rossem, W. Johan Lie, Ewout A. Kouwenhoven, A.J. Staal-van den Brekel, Nike Hanneman, Roxane Heller-Baan, V.J. Noyez
Abstract
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, P noninferior < .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%; P noninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; P noninferior = .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.