Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer

Lung cancer is the number one cause of death due to cancer worldwide. According to the World Health Organization, it accounted for 1.69 million new cases in 2015, whereas in Europe, 20.8% of all deaths due to cancer (>266 000 cases) were attributable to lung cancer in 2011 [1, 2].

Accurate lung cancer staging is fundamental to plan optimum individualised therapy. Extensive mediastinal staging is recommended before surgical resection for patients with non-small cell lung cancer (NSCLC) and clinical/radiological stage I or II disease [3]. Previous guidelines published by European Society of Gastrointestinal Endoscopy in cooperation with the European Respiratory Society and the European Society of Thoracic Surgeons recommend that endosonography should be performed over surgical staging as the initial procedure for mediastinal nodal staging in patients with suspected or proven NSCLC and abnormal mediastinal and/or hilar nodes at computed tomography (CT) and/or fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT, (recommendation grade A) [4]. However, recent studies report relatively low sensitivity for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to detect mediastinal disease in clinical N0 PET-CT, while others report a significant risk of mediastinal nodal involvement in patients classified as clinical N1 by PET-CT [5–10].

This article reports the findings of a prospective clinical trial by Decaluwé et al. [11]. Investigators attempted to evaluate preoperatively the sensitivity of video-assisted mediastinoscopy (VAM) or VAM–lymphadenectomy (VAM(LA)) in mediastinal staging of operable and resectable suspected NSCLC and clinical N1 disease (cN1).

Conventional mediastinoscopy has been considered the gold-standard method for preoperative mediastinal staging in NSCLC patients. Its sensitivity depends on the number of lymph nodes and the amount of lymph node tissue resected; this results in false-negative rates that have been reported to be as high as 10% [12]. VAM(LA) is a minimally invasive technique of systematic mediastinal lymph node dissection. Optic fibres are integrated to conventional mediastinoscopes, and further modifications are made in the mediastinoscope's working channel allowing bimanual surgery, optimum visualisation and access to lymph nodes. The technique was developed in an attempt to achieve maximum accuracy and radical lymph node excision in a minimally invasive manner, thus reducing the high false-positive rates of conventional mediastinoscopy. In VAM, lymph nodes of different stations are assessed and sampled, but not necessarily removed completely, as during VAM(LA) [13, 14].

Patients, methods, study design and end-points

For this prospective non-randomised multicentre clinical trial, inclusion criteria were age ≥18 years, operable suspected NSCLC and cN1 disease based on FDG-PET-CT. cN1 disease was defined as enlarged lymph nodes (≥10 mm on the largest short axis on CT) or a FDG-PET-positive lymph node in an N1 position, as described in the International Association for the Study of Lung Cancer lymph node map [15]. FDG-PET-CT lymph node positivity was defined as FDG uptake higher than background uptake in the mediastinal blood pool. Conversely, patients with unresectable neoplasia, known medical history of cancer with previous treatment, cT3 or cT4 disease based on TNM classification or previous endobronchial ultrasound of mediastinal lymph nodes were excluded from the study.

Sensitivity in detecting mediastinal nodal involvement (N2 disease) by VAM(LA) was the primary end-point. Sensitivity was defined as the proportion of patients with positive mediastinal staging by VAM(LA) out of all patients with mediastinal nodal disease. Secondary endpoints were negative predictive value (NPV), accuracy, negative post-test probability and assessment of the prevalence of N2/3 disease.