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If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods\/design<\/jats:title>\n                <jats:p>This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET\/CT demonstrates \u2018bulky N2-N3\u2019 disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2\u00a0years after start of treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>The trial is registered at the Netherlands Trial Register on July 6th, 2017 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.trialregister.nl\/trialreg\/admin\/rctview.asp?TC=6528\">NTR 6528<\/jats:ext-link>).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12893-018-0359-6","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T04:17:26Z","timestamp":1526617046000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial"],"prefix":"10.1186","volume":"18","author":[{"name":"MEDIASTrial study group","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelle E.","family":"Bousema","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel G. 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All participating centers signed the research contract prior to start inclusion. Before randomization, written informed consent will be obtained from all patients.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"27"}}