Abstract
Background
Variability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature. Patients’ preferences on this topic have, however, been underexposed so far.
Methods
An internet-based questionnaire was distributed among MEDIASTrial participants (NTR6528, randomization of patients to mediastinoscopy or not in the case of negative endosonography). Literature, expert opinion and patient interviews resulted in five attributes: the risk of a futile lung resection (oncologically futile in case of unforeseen N2 disease), the length of the staging period, resection of the primary tumor, complications of staging procedures and the mediastinoscopy scar. The relative importance (RI) of each attribute was assessed by using adaptive conjoint analysis and hierarchical Bayes estimation. A treatment trade-off was used to examine the acceptable proportion of avoided futile lung resections to cover the burden of confirmatory mediastinoscopy.
Results
Ninety-seven patients completed the questionnaire (57%). The length of the staging period was significantly the most important attribute (RI 26.24; 95% CI: 25.05–27.43), followed by the risk of a futile surgical lung resection (RI 23.44; 95% CI: 22.28–24.60) and resection of the primary tumor (RI 22.21; 95% CI: 21.09–23.33). Avoidance of 7% (IQR 1– >14%) futile lung resections would cover the burden of confirmatory mediastinoscopy, with a dichotomy among patients always (39%) or never (38%) willing to undergo confirmatory mediastinoscopy after N2 and N3-negative endosonography.
Conclusion
Although a strong dichotomy among patients always or never willing to undergo confirmatory mediastinoscopy was found, the length of the staging period was the most important attribute in invasive mediastinal staging according to patients with resectable NSCLC.
Trial Registration
Not applicable.
Abbreviations
NSCLC, non-small cell lung cancer; RI, relative importance; EBUS, endobronchial ultrasonography; EUS, endoscopic ultrasonography; ACA, adaptive conjoint analysis; TTM, treatment trade-off method; IQR, interquartile range; CI, confidence interval.
List of Definitions
EBUS(-TBNA) endobronchial ultrasound guided transbronchial needle aspiration: Investigation of mediastinal and hilar lymph nodes with a linear ultrasound probe via the airways with the possibility of nodal sampling under real-time ultrasound control.
EUS(-FNA) endoscopic ultrasound guided fine needle aspiration: Investigation of mediastinal lymph nodes with a linear ultrasound probe via the esophagus with the possibility of nodal sampling under real-time ultrasound control.
Futile surgical lung tumor resection: A surgical lung tumor resection was deemed oncologically futile in case unforeseen N2 (macro-metastases or multi-level) disease was detected after surgery, as overall survival of these patients is generally not extended as a result of the surgery.
Mediastinal staging: Invasive mediastinal nodal staging to determine the nodal status of lung cancer by using EBUS, EUS and/or mediastinoscopy.
Mediastinoscopy: Surgical procedure under general anesthesia to examine mediastinal lymph nodes, located paratracheal and subcarinal, with the possibility to take surgical biopsies.
Negative endosonography: Endosonographic examination of mediastinal lymph nodes by using EBUS-TBNA and/or EUS-FNA showing no pathologically proven N2 or N3 lymph node metastases.
Unforeseen N2: Pathologically proven N2 disease resulting from mediastinal lymph node dissection at time of tumor resection, not detected by clinical staging including endosonography or mediastinoscopy (if performed).
Data Sharing Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ethics Approval and Consent to Participate
This study was performed in accordance with the declaration of Helsinki, 64th WMA General Assembly, Fortaleza, Brazil, October 2013 and in accordance with the Medical Research Involving Human Subjects Act (WMO, the Netherlands). The medical ethical committee of Máxima MC approved the study protocol, and written informed consent was obtained from all patients.
Acknowledgments
Beside the authors of this article the following steering group members and local investigators are members of the MEDIASTrial study group:
Nicole E Papen-Botterhuis
Department of Research and Innovation, Máxima MC, Veldhoven, the Netherlands
Maggy Youssef-El Soud
Department of Pulmonary Medicine, Máxima MC, Veldhoven, the Netherlands
Wim J van Boven
Department of Cardiothoracic Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Johannes MA Daniels
Department of Pulmonary Medicine, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
David J Heineman
Department of Surgery, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
Department of Cardiothoracic Surgery, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
Harmen R Zandbergen
Department of Cardiothoracic Surgery, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
Pepijn Brocken
Department of Pulmonary Medicine, HagaZiekenhuis, Den Haag, the Netherlands
Thirza Horn
Department of Surgery, HagaZiekenhuis, Den Haag, the Netherlands
Willem H Steup
Department of Surgery, HagaZiekenhuis, Den Haag, the Netherlands
Jerry Braun
Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands
Rajen SRS Ramai
Department of Pulmonary Medicine, Leiden University Medical Center, Leiden, the Netherlands
Naomi Beck
Dutch Institute for Clinical Auditing, Leiden, the Netherlands
Nicole P Barlo
Department of Pulmonary Medicine, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands
Martijn van Dorp
Department of Surgery, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands
W Hermien Schreurs
Department of Surgery, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands
Anne-Marie C Dingemans
Department of Pulmonary Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
Jos G Maessen
Department of Cardiothoracic Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
Erik HFM van der Heijden
Department of Pulmonary Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
Ad FTM Verhagen
Department of Cardiothoracic Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
Niels JM Claessens
Department of Pulmonary Medicine, Rijnstate ziekenhuis, Arnhem, the Netherlands
Jan-Willem HP Lardenoije
Department of Surgery, Rijnstate ziekenhuis, Arnhem, the Netherlands
Birgitta I Hiddinga
Department of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Caroline van de Wauwer
Department of Cardiothoracic Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Anthonie J van der Wekken
Department of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Wessel E Hanselaar
Department of Pulmonary Medicine, Franciscus Gasthuis en Vlietland, Rotterdam, the Netherlands
Robert TJ Kortekaas
Department of Surgery, Franciscus Gasthuis en Vlietland, Rotterdam, the Netherlands
Martin P Bard
Department of Pulmonary Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands
Herman Rijna
Department of Surgery, Spaarne Gasthuis, Hoofddorp, the Netherlands
Gerben P Bootsma
Department of Pulmonary Medicine, Zuyderland Medical Center, Heerlen, the Netherlands
Yvonne LJ Vissers
Department of Surgery, Zuyderland Medical Center, Heerlen, the Netherlands
Eelco J Veen
Department of Surgery, Amphia, Breda, the Netherlands
Cor H van der Leest
Department of Pulmonary Medicine, Amphia, Breda, the Netherlands
Emanuel Citgez
Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
Eino B van Duyn
Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands
Geertruid MH Marres
Department of Surgery, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
Eric R van Thiel
Department of Pulmonary Medicine, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands
Paul E van Schil
Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Antwerp, Belgium
Jan P van Meerbeeck
Department of Pulmonary Medicine, Antwerp University Hospital, Antwerp, Belgium
Niels Smakman
Department of Surgery, Diakonessenhuis, Utrecht, the Netherlands
Femke van der Meer
Department of Pulmonary Medicine, Diakonessenhuis, Utrecht, the Netherlands
Mohammed D Saboerali
Department of Pulmonary Medicine, Beatrixziekenhuis, Gorinchem, the Netherlands
Anne Marie Bosch
Department of Surgery, Ziekenhuis Gelderse Vallei, Ede, the Netherlands
Wouter K de Jong
Department of Pulmonary Medicine, Ziekenhuis Gelderse Vallei, Ede, the Netherlands
Charles C van Rossem
Department of Surgery, Maasstad Ziekenhuis, Rotterdam, the Netherlands
W Johan Lie
Department of Pulmonary Medicine, Maasstad Ziekenhuis, Rotterdam, the Netherlands
Ewout A Kouwenhoven
Department of Surgery, ZiekenhuisGroep Twente, Almelo, the Netherlands
A Jeske Staal-van den Brekel
Department of Pulmonary Medicine, ZiekenhuisGroep Twente, Almelo, the Netherlands
Nike M Hanneman
Department of Surgery, Ikazia Ziekenhuis, Rotterdam, the Netherlands
Roxane Heller-Baan
Department of Pulmonary Medicine, Ikazia Ziekenhuis, Rotterdam, the Netherlands
Valentin JJM Noyez
Department of Vascular and Thoracic Surgery, Sint-Maarten General Hospital, Mechelen, the Netherlands
Author Contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.
Disclosure
Dr Bousema and Dr van den Broek report research grants from ZonMw and the Dutch Cancer Society, during the conduct of this study. Prof. Dr Annema reports non-financial support from Hitachi Medical systems and Pentax and a grant from Cook Medical, outside the submitted work. The authors report no other conflicts of interest in this work.