Adjuvant immunotherapy in resectable non-small cell lung cancer with nodal downstaging.

OBJECTIVES: To determine whether prognosis after neoadjuvant chemo-immunotherapy is better predicted by pretreatment clinical nodal stage or post-treatment pathological nodal status, and whether patients downstaged to ypN0 have outcomes comparable to those with primary N0. METHODS: We conducted a multicenter retrospective cohort study of patients with resectable NSCLC treated with neoadjuvant chemo-immunotherapy followed by curative-intent surgery between January 2020 and December 2024. Patients were categorized as Natural N0 (cN0/ypN0), Downstaged N0 (cN+/ypN0), or ypN + according to baseline clinical and postoperative pathological nodal status. RFS and OS were analyzed using Kaplan-Meier and Cox regression methods. Subgroup analyses were performed in ypN0 patients to assess the association of adjuvant immunotherapy with survival. RESULTS: A total of 413 patients were included, and 207 (67.0%) with clinical nodal metastasis achieved nodal downstaging to ypN0. The overall MPR and pCR rates were 62.5% and 35.8%, respectively. After a median follow-up of 29.2 months, 2-year RFS and OS rates were 78.0% and 93.3%. Downstaged N0 had survival comparable to Natural N0, whereas ypN + was associated with worse RFS. In multivariable analysis, ypN + independently predicted poor recurrence-free survival (HR 2.86, 95% CI 1.40-5.84). Among ypN0 patients, adjuvant immunotherapy was not associated with improved RFS or OS. CONCLUSIONS: Post-treatment nodal status is a key prognostic marker after neoadjuvant chemo-immunotherapy in resectable NSCLC. Patients with ypN0 had comparable outcomes regardless of clinical nodal stage, and selected ypN0 patients may not require adjuvant immunotherapy.