The Value of Surgical Mediastinal Staging in Clinical N1 Lung Cancer

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for mediastinal staging of 38% (ITT analysis), while the prevalence of mediastinal nodal disease was 24% (unpublished data Aster 2) 2.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.

Inclusion criteria

(Suspected) NSCLC Medical operable and surgical resectable cT1, cT2 selected cT3 (i.e. intraparenchymal tumour >7cm, T3 chest wall, or T3 based on additional nodule in the lobe of the primary tumour) cN1 based on CT or PET 18 years or older Informed Consent

Exclusion criteria

History of mediastinoscopy No integrated FDG PET/CT available No videomediastinoscopy available EBUS/EUS for mediastinal staging of present N1 disease cN2: mediastinal nodes enlarged on CT or Pet positive invasion of mediastinal pleura invasion of phrenic nerve invasion of parietal pericardium tumour in main bronchus less than 2cm form the main carina cT4 cM1 former therapy for lung cancer (chemotherapy, radiotherapy, surgery) technical contraindication for videomediastinoscopy ( eg extreme kyphosis, cutaneous tracheostomy, extreme goiter) pregnancy inability to consent