Impact of Residual Mediastinal Nodal Disease After Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer

Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58–69]). Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p < 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies.