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

Background/aim: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.