Thorough Lymphadenectomy Impairs Immunotherapy Outcomes for Postoperative Intrathoracic Recurrence of Non-small Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for recurrent non-small cell lung cancer (NSCLC). However, the factors predicting their efficacy in postoperative recurrence remain unclear. We retrospectively analyzed 30 patients who underwent complete surgical resection of NSCLC and subsequently received ICI monotherapy for recurrence. Clinicopathological factors, including the programmed death ligand 1 (PD-L1) expression and number of dissected lymph nodes (DLNs), were evaluated for their association with the treatment response and prognosis. The high expression of PD-L1 (≥50%) in surgical specimens was significantly associated with higher response rates, prolonged progression-free survival (PFS), and overall survival (OS) after the initiation of ICI therapy. In contrast, patients with ≥15 DLNs had a significantly shorter PFS than those with <15 DLNs, particularly in patients without extrathoracic recurrence. A multivariate analysis identified the expression of PD-L1, the number of DLNs, and the presence of extrathoracic metastasis as independent prognostic factors for ICI-PFS. Extensive lymphadenectomy may worsen the prognostic outcomes of ICI monotherapy, possibly by impairing tumor-draining lymph node-mediated immunity. These findings highlight the importance of lymphatic preservation and support the clinical rationale for neoadjuvant ICI therapy for resectable NSCLC.