Mediastinal re-staging

Inspired by a controversy session at ELCC 2025, Dr Elena Prisciandaro and Prof Paul Van Schil, both thoracic surgeon respectively at the Hôpital Erasme in Brussels and at the Antwerp University Hospital, discuss the role of invasive mediastinal restaging for patients with non-small-cell lung cancer (NSCLC) following neoadjuvant chemo-immunotherapy.

The interest for mediastinal restaging stems in older clinical trials showing a very poor prognosis for patients with persistent N2 disease on mediastinoscopy in NSCLC patients who received neoadjuvant chemotherapy, or chemoradiotherapy. Unfortunately, however, the the different clinical trials evaluating neoadjuvant or perioperative (chemo)immunotherapy in these patients, only used CT scans to assess the mediastinum after the neoadjuvant treatment. By now, however, it is has become clear that excessive inflammation and pseudoprogression after neoadjuvant chemoimmunotherapy makes CT a very insensitive technique to evaluate persistent nodal involvement. A further consequence of this is that many medical oncologists no longer appreciate the importance of mediastinal restaging. 

Most thoracic surgeons, however, still see invasive mediastinal restaging as a standard of care. In fact, data clearly indicate that patients with a truly negative mediastinum on invasive restaging generally have a good prognosis, while patients with persistent N2 disease tend to do very bad. Interestingly, patients with a false negative result on a second mediastinoscopy (i.e., no involvement on mediastinoscopy, but positive nodes found during surgery) have an intermediate prognosis. Based on this, Prof Van Schil urges for a thorough baseline mediastinal evaluation using EBUS, followed by a mediastinoscopy after the neoadjuvant therapy. 

Exactly what to do in patiens with persistent N2 disease is currently subject to debate. For patients with persistent N2B disease (i.e., multilevel nodal involvement) there seems to be a consensus that surgery will probably not improve the prognosis. In patients with single station involvement, however, surgery may still be an option as long as an R0 resection is deemed feasible. The exact role for radiotherapy and adjuvant immunotherapy in both these groups is yet to be elucidated. 

On a final note, Prof Van Schil indicates that the classification into N2A and N2B disease has only recently been introduced, following the publication of the 9th TNM edition for lung cancer staging. This staging system is based on patients treated between 2011 and 2019 and as a result, only a minority of them received neoadjuvant chemoimmunotherapy. For more detailed information on the prognostic relevance of these stages in the current chemo-immunotherapy era we will therefore have to wait for the updated 10th edition of the TNM classification.