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Prognostic significance of ypN status after neoadjuvant chemoimmunotherapy in resectable NSCLC: a systematic review
Huan Shao1, Lingyun Zou2, Xiaojiao Zhu1
1Department of Oncology, The First People's Hospital of Jiande, Jiande, China.
Background:
Neoadjuvant chemoimmunotherapy has become an important treatment strategy for resectable non-small cell lung cancer (NSCLC), yet postoperative relapse remains common. Although pathological response is increasingly used for prognostication, the prognostic value of post-treatment nodal status remains unclear. We therefore conducted a systematic review and meta-analysis to evaluate the association between ypN status and survival outcomes after neoadjuvant chemoimmunotherapy in resectable NSCLC.
Methods:
In accordance with PRISMA 2020 guidelines, PubMed, Web of Science, Scopus, Embase, and the Cochrane Library were searched from inception to February 26, 2026. Studies reporting survival outcomes stratified by pathological nodal response in patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy were included. Overall survival (OS) was prespecified as the primary outcome. Disease-free survival (DFS) was considered a secondary outcome, while recurrence-free survival (RFS) was summarized descriptively when quantitative pooling was not feasible. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models according to heterogeneity.
Results:
Two studies were included in the primary meta-analysis of OS. Across prespecified clinically comparable but non-identical nodal-response contrasts, unfavorable post-treatment nodal status was associated with significantly poorer OS (pooled HR 4.75, 95% CI 2.38 - 9.47; P < 0.00001; I² = 0%). A similar association was observed for DFS (pooled HR 3.54, 95% CI 1.71-7.33; P = 0.0007; I² = 0%). Sensitivity analyses showed consistent results. For RFS, only one study provided extractable data, suggesting that combined major pathological response (MPR)-ypN classification may further stratify prognosis, with the non-MPR ypN+ group showing the poorest outcome.
Conclusions:
Across prespecified clinically comparable but non-identical nodal-response contrasts, unfavorable post-treatment nodal status was associated with poorer survival outcomes in resectable NSCLC. Because the pooled OS and DFS analyses each included only two retrospective studies, these findings should be interpreted cautiously pending prospective validation with standardized pathological classifications and uniform survival endpoints.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/, identifier CRD420261353461.
