Assessment of Surgical sTaging vs Endoscopic Ultrasound in Lung Cancer: a Randomized Clinical Trial (ASTER Study)

Study Overview
=================
Brief Summary
-----------------
Lung cancer is one of the most prevalent cancers and has a very high mortality. Both treatment and prognosis depend on the staging. Surgical staging of the mediastinum mainly by means of a cervical mediastinoscopy is the gold standard. Mediastinal staging is however a field that undergoes a fast technological development. Transesophageal ultrasound guided fine-needled aspiration (EUS-FNA) and an endobronchial ultrasound guided transbronchial fine-needled aspiration (EBUS-TBNA) are two complementary endoscopic ultrasound techniques which together allow cytological analysis of all mediastinal lymph nodes. This means that the combination of both techniques enables a complete (bilateral) mediastinal investigation (N2 and N3, except para-aortal station 6). Hypothesis: complete endoscopic ultrasound staging identifies more patients with locally advanced disease compared to surgical staging (current standard of care). Study design: A randomized controlled multi-center double arm diagnostic phase III trial, in which patients are randomly assigned to either surgical staging (arm B) or endoscopic ultrasound staging with both EUS-FNA and EBUS-TBNA (arm A). Arm A: Examination by EUS-FNA and EBUS-TBNA. These techniques are performed in an outpatient one session setting under conscious sedation and take together about 30 to 60 minutes. If no metastasis are shown, the patient undergoes a surgical staging procedure (for confirmation). For reasons of convenience and patient-comfort, the EUS-FNA investigation is performed before the EBUS-TBNA. Arm B: Surgical staging with either cervical mediastinoscopy, parasternal mediastinoscopy, thorascopic mediastinal exploration or exploratory thoracotomy, performed according to institutional practice. Patients in whom no lymph node metastasis are found proceed to thoracotomy with systematic lymph node sampling to obtain an accurate intraoperative mediastinal staging. Primary outcome: The assessment of N2-N3 lymph node metastases.

Official Title
-----------------
Complete Echo-Endoscopic Staging of Lung Cancer vs Surgical Staging: a Randomized Clinical Trial

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Procedure: Endoscopic ultrasound staging
* Procedure: Surgical staging


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consecutive patients with NSCLC or with a clinical suspicion for lung cancer in whom mediastinal lymph node invasion (either N2 or N3) is suspected based on the available thoracic imaging Pending the results of the mediastinal staging, the patient is otherwise considered a candidate for a surgical treatment with the intention to cure (this is a resectable tumor) The patient is clinically fit for diagnostic surgery (this is an operable patient) No distant metastasis after routine clinical work up Provision of a written informed consent Exclusion Criteria: Former therapy (chemotherapy or radiotherapy or surgery) for lung cancer Reasons because of which the patient is unable to swallow the EUS-instrument (e.g. Zenker Divertikel, unexplained esophageal stenosis) or because of which the patient is unable to undergo a bronchoscopy Patients who, based on available thoracic imaging, are unlikely to be staged accurately by any surgical staging procedure (mediastinoscopy/ - tomy, VATS) Respiratory insufficiency or other contra-indications for bronchoscopy Concurrent other malignancies Uncorrected coagulopathy Study cannot be discussed with the patient (e.g. mental disorder)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Endoscopic ultrasound staging | Procedure: Endoscopic ultrasound staging<br>* Endoscopic ultrasound staging with both EUS-FNA and EBUS-TBNA<br>|
| Active Comparator: 2<br>Surgical staging | Procedure: Surgical staging<br>* Surgical staging<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| We hypothesize that the combination of EUS and EBUS in an out-patient one-session setting is more sensitive for the detection of locally advanced disease (N2/N3) compared to surgical staging (standard of care) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of mediastinal tumour invasion (T4) |  |  | 
| Assessment of the rate of avoided surgical procedures (arm A) |  |  | 
| Assessment of the negative predictive value |  |  | 
| Assessment of the difference in the cost for lymph node staging |  |  | 
| Assessment of the complication rates |  |  | 
| Assessment of the rate of futile thoracotomies |  |  | 
| Assessment of quality of life (EQ5D) |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
(suspected) Non Small Cell Lung Cancer