The Value of Surgical Mediastinal Staging in Clinical N1 Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Observational

Summary: 
      In case of PET or CT based cN1 (suspected) NSCLC, ESTS guidelines propose mediastinal staging
      by echo-endoscopy OR mediastinoscopy. Recent data show a sensitivity of less than 50% for
      echo-endoscopy to detect N2 disease in cN1 NSCLC patients, while prevalence of mediastinal
      nodal disease was 24% (unpublished data Aster II).2 The investigators plan to perform a
      prospective multicentric observational study to measure the sensitivity of mediastinal
      staging by video-assisted mediastinoscopy (VAM) in cN1 operable and resectable (suspected)
      NSCLC patients.
    

Detailed description: 
      Few reports in the literature evaluated the final pathological stage distribution of patients
      with resectable and operable non-small cell lung cancer (NSCLC) with clinical stage cN1.
      These retrospective series demonstrated that patients with computed tomography (CT) based cN1
      often had clinically occult mediastinal lymph node metastases (N2/3 disease). Hishida et al.
      reported that 30% of 143 patients with cN1 were diagnosed N2/3 by mediastinoscopy3. Watanabe
      et al. reported that 37% of 168 patients with cN1 were diagnosed N2/3 by mediastinoscopy 4.
      Adding FDG-positron emission tomography (PET) to CT might enable the detection of N2/3
      disease among these cN1 patients, but negative PET findings do not necessarily exclude N2/3
      disease. Kim et al reported that 19,2 % of 99 patients with cN1, in whom cN2 was ruled out by
      PET-CT scan, were found to have pathologic N2 disease at pulmonary resection with mediastinal
      lymph node dissection.5 In conclusion, 20-30% of patients with cN1 nodes on imaging, and
      normal sized FDG-negative mediastinal lymph nodes on CT and PET have malignant involvement in
      their mediastinal nodes.

      The ACCP guidelines state that invasive preoperative mediastinal staging should be performed
      in these cN1 patients 6. The updated ESTS guidelines recommend mediastinal staging by
      echo-endoscopic or mediastinoscopy.1 Non-randomized trials suggested the potential of linear
      endosonography for mediastinal staging 7-9. However, the patients with cN1 disease form only
      a minority in these studies. A recently performed prospective ASTER 2 trial (N=100) showed a
      sensitivity of echo-endoscopic for mediastinal staging of 38% (ITT analysis), while the
      prevalence of mediastinal nodal disease was 24% (unpublished data Aster 2) 2. The conclusion
      made by ASTER 2 is that a negative endosonography must be followed by a VAM. However, the
      investigators consider such double approach not cost-effective in a setting with N2
      prevalence <30%. Therefore, it seems reasonable to perform a VAM instead of an endosonography
      in cN1 patients, which is one of the proposed strategies in the recent ESTS guidelines.1
      However, there is no prospective study to date that assessed the sensitivity, NPV and
      accuracy of VAM in a well-defined group of cN1 patients.

      Several publications have demonstrated a lobe-specific mediastinal nodal drainage for upper
      versus lower lobe NSCLC. Shapiro et al conclude that in early lung cancer, including cN1
      disease, lobe-specific mediastinal dissection is warranted 10. However, in this study the
      only patient with a positive subcarinal node, upper lobe tumour, and negative superior
      mediastinal nodes had positive N1 nodes. To the investigators knowledge there is no study
      focussing on mediastinal nodal dissemination patterns in cN1 patients.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with operable and resectable cT1-2- selectedT3 cN1 (suspected) NSCLC. (selected T3
        = intraparenchymal tumour >7cm or T3 chest wall or T3 additional nodule, excluding
        mediastinal invasion or invasion of the main bronchus < 2cm from the carina)
      
Keywords: Lung cancer; Surgery; Videomediastinoscopy