Systematic review and meta-analysis on neoadjuvant chemoimmunotherapy for resectable NSCLC

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Frontiers in Medicine Published May 22, 2026 Medically reviewed May 22, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that unfavorable post-treatment nodal status after neoadjuvant chemoimmunotherapy is associated with poorer survival in resectable NSCLC.

This is a systematic review and meta-analysis of evidence on neoadjuvant chemoimmunotherapy for patients with resectable non-small cell lung cancer. The authors synthesized findings from retrospective studies on post-treatment nodal status and survival outcomes. The meta-analysis found unfavorable post-treatment nodal status was associated with significantly poorer overall survival, with a pooled HR of 4.75 (95% CI 2.38 to 9.47; P < 0.00001; I² = 0%). Unfavorable nodal status was also associated with poorer disease-free survival, with a pooled HR of 3.54 (95% CI 1.71 to 7.33; P = 0.0007; I² = 0%). The review noted that combined major pathological response and ypN classification may further stratify prognosis, with the non-MPR ypN+ group showing the poorest outcome. The authors highlighted key limitations, including that pooled analyses for overall and disease-free survival each included only two retrospective studies. They concluded that findings should be interpreted cautiously pending prospective validation with standardized pathological classifications and uniform survival endpoints. Practice relevance was not reported.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundNeoadjuvant 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.MethodsIn 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.ResultsTwo 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.ConclusionsAcross 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 registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261353461.