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Published on: February 27, 2026
Adjuvant immunotherapy in resectable non-small cell lung cancer with nodal downstaging
Mengzhen You1, Yang Pan2, Cien Sun3
1Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China; School of Medicine, Zhejiang University, Hangzhou, PR China.
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.