Invasive mediastinal nodal staging of resectable non-small cell lung cancer

Patients with resectable non-small cell lung cancer and increased risk of mediastinal nodal involvement require invasive staging to exclude patients with N2-3 metastases for surgical resection. The current guidelines recommend endosonography as initial staging procedure followed by confirmatory mediastinoscopy in case of absence of N2-3 metastases after endosonography. The role of confirmatory mediastinoscopy is however under debate due to its limited additional diagnostic value and its associated morbidity, hospital admission and delay in definite lung cancer treatment.
The first part of the thesis focusses on the daily practice of invasive mediastinal nodal staging and adherence to the (inter)national guidelines. We performed a multicenter retrospective analysis, a nationwide Dutch Lung Cancer Audit analysis and a nationwide Netherlands Cancer Registry analysis which showed poor adherence to the guidelines regarding performance of endosonography followed by confirmatory mediastinoscopy. The use of endosonography significantly increased over the years, while the use of mediastinoscopy decreased, despite these changes unforeseen N2 metastases after resection remained stable.
The second part focusses on the value of confirmatory mediastinoscopy after tumor negative endosonography. A patient preferences study showed that the length of the staging period was significantly the most important attribute. A meta-analysis showed comparable unforeseen N2 results after staging by endosonography with or without confirmatory mediastinoscopy. The randomised MEDIASTrial ultimately showed that on the basis of non-inferiority in unforeseen N2 (as surrogate marker of clinically relevant diagnostic accuracy) confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.