Rethinking Invasive Mediastinal Staging in the Era of Neoadjuvant Immune-Checkpoint Inhibitors

Over the past several decades, the management of nonmetastatic nonsmall cell lung cancer (NSCLC) has centered on identifying patients eligible for upfront surgical treatment. This selection has traditionally relied on multidisciplinary assessments of clinical operability and oncologic resectability, with the latter depending primarily on mediastinal lymph node evaluation, a key prognostic factor in determining whether patients should be directed toward upfront surgery or definitive chemoradiotherapy. The recent incorporation of immune checkpoint inhibitors (ICIs) into standard neoadjuvant therapy has transformed this paradigm. By significantly enhancing pathologic response and improving survival across the full spectrum of N2 disease, neoadjuvant ICI therapy is reshaping the prognostic weight traditionally assigned to mediastinal nodal involvement, challenging long-standing staging practices. Rather than serving primarily to exclude patients from surgery, mediastinal assessment in the immunotherapy era may play a more selective role in baseline risk stratification while also potentially gaining new roles, such as in the evaluation of treatment response and nodal downstaging, which could support broader refinements in clinical decision-making. This update synthesizes emerging evidence and evolving clinical concepts to re-examine mediastinal assessment in the immunotherapy era, with implications for clinical decision-making and future trial design in nonmetastatic NSCLC.