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

Abstract

BackgroundIn case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. 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.Methods/designThis 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 ‘bulky N2-N3’ 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 years after start of treatment.DiscussionResults 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.Trial registrationThe trial is registered at the Netherlands Trial Register on July 6th, 2017 (NTR 6528).Electronic supplementary materialThe online version of this article (10.1186/s12893-018-0359-6) contains supplementary material, which is available to authorized users.

Predictive Value of Endobronchial Ultrasound Strain Elastography in Mediastinal Lymph Node Staging: The E-Predict Multicenter Study Results

“…This is already a major step forward when compared to a 10-mm cutoff, which would equal to as much as 25.6% of malignant lymph nodes being missed. Ideally, lymph nodes smaller than 8 mm should also be considered for aspiration, but the more recent large multicenter trials have used this 8-mm cut-off value successfully [7,19]. We recommend further research on this subject to enable adjustment of the guidelines accordingly.…”

Unforeseen N2 Disease after Negative Endosonography Findings with or without Confirmatory Mediastinoscopy in Resectable Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…The MEDIASTrial, a multicenter randomized trial evaluating the impact on unforeseen N2 disease by comparing mediastinal staging strategies with or without confirmatory mediastinoscopy might shed light on this issue (MEDIASTrial, NTR6528). 62…”

B Cells and Tertiary Lymphoid Structures Influence Survival in Lung Cancer Patients with Resectable Tumors

“…In case of negative results, a surgical exploration of the mediastinum: cervical video-assisted mediastinal lymphadenectomy (VAMLA) and/or anterior mediastinotomy were performed, the latter depending on the location of the suspected nodes. Notwithstanding, in all surgical cases, intra-operative systematic hilar and mediastinal lymphadenectomy (at least, ipsilateral paratracheal, subcarinal, and ipsilateral pulmonary ligament) was performed as previously recommended [40,41]. Standard clinical guidelines were used to establish the selection of patients and contraindications for thoracic surgery as previously described [42].…”