可切除非小细胞肺癌新辅助化疗免疫治疗后ypN状态的预后意义：系统综述与荟萃分析

摘要(中文译文)

新辅助化学免疫治疗已成为可切除非小细胞肺癌（NSCLC）的重要治疗策略，但术后复发仍较为常见。尽管病理缓解越来越多地用于预后判断，但治疗后淋巴结状态的预后价值仍不明确。因此，我们开展了一项系统评价和荟萃分析，以评估可切除NSCLC患者接受新辅助化学免疫治疗后ypN状态与生存结局之间的关联。按照PRISMA 2020指南，检索了PubMed、Web of Science、Scopus、Embase和Cochrane Library自建库至2026年2月26日的文献。纳入报告可切除NSCLC患者接受新辅助化学免疫治疗后按病理淋巴结缓解分层的生存结局的研究。总生存期（OS）被预设为主要结局。无病生存期（DFS）被视为次要结局，而当无法进行定量合并时，无复发生存期（RFS）以描述性方式总结。根据异质性采用固定效应或随机效应模型合并风险比（HR）及其95%置信区间（CI）。主要OS荟萃分析纳入了两项研究。在预设的临床可比但不完全相同的淋巴结缓解对比中，不利的治疗后淋巴结状态与显著更差的OS相关（合并HR 4.75，95% CI 2.38-9.47；P < 0.00001；I² = 0%）。DFS也观察到类似的关联（合并HR 3.54，95% CI 1.71-7.33；P = 0.0007；I² = 0%）。敏感性分析显示结果一致。对于RFS，仅有一项研究提供了可提取的数据，提示主要病理缓解（MPR）与ypN分类联合可能进一步对预后进行分层，其中非MPR的ypN+组结局最差。在预设的临床可比但不完全相同的淋巴结缓解对比中，不利的治疗后淋巴结状态与可切除NSCLC更差的生存结局相关。由于合并的OS和DFS分析各自仅纳入两项回顾性研究，这些发现应谨慎解读，尚待采用标准化病理分类和统一生存终点进行前瞻性验证。https://www.crd.york.ac.uk/prospero/，注册号CRD420261353461。

Abstract

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. 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. 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. 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. https://www.crd.york.ac.uk/prospero/, identifier CRD420261353461.

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