MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy

Rationale: NSCLC patients with increased risk of mediastinal lymph node metastases should undergo cervical mediastinoscopy to rule out mediastinal nodal spread, despite negative endobronchial and/or endoscopic ultrasound (EBUS/EUS-B). It is unknown whether additional mediastinoscopy can be omitted without compromising important outcomes.



Research question: Will omitting cervical mediastinoscopy in patients with negative staging by EBUS/EUS-B be non-inferior to the strategy with additional mediastinoscopy regarding the occurrence of unforeseen N2 disease after definite surgery and be superior regarding cost-effectiveness?



Study design: Multicenter parallel randomized trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in patients with suspected NSCLC. All randomized patients will be followed up for 2 years.



Study population: Patients are eligible for inclusion in this trial when they meet the following eligibility criteria:

1. Diagnosed (pathological proof) or suspected (based on CT and FDG-PET) with NSCLC.

2. CT and FDG-PET scan have excluded distant metastasis or an irresectable primary tumour.

3. One of the criteria defining the need for mediastinal staging are met according to the European and Dutch guidelines:

- PET/CT of the chest demonstrates CT-enlarged or FDG-PET avid hilar or mediastinal lymph nodes.

- CT demonstrates central location of the primary tumour

- FDG-PET demonstrates a PET non avid primary tumour

- Peripheral lung tumours larger than 3cm on CT

Mediastinal staging of NSCLC by EBUS/EUS-B with and without additional cervical mediastinoscopy are both effective diagnostic strategies for assessment of mediastinal lymph node metastases. However, omitting mediastinoscopy comprises no extra waiting time until definite surgery, no additional required 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.

Baseline, 1 week after mediastinoscopy (as performed), 2 weeks, 4 weeks, 3 months, 6 months, 12 months and 24 months after start treatment.

Intervention: After negative EBUS/EUS-B patients will undergo immediate anatomic resection of the primary tumour.



Usual care: According to current national and international guidelines, patients will first undergo cervical mediastinoscopy after negative EBUS/EUS-B.