可切除食管鳞状细胞癌新辅助治疗中同步与序贯免疫检查点抑制的比较：一项系统评价和荟萃分析

摘要(中文译文)

免疫检查点抑制剂（ICI）正日益被纳入可切除食管鳞状细胞癌（ESCC）的新辅助治疗，然而ICI给药的最佳时机仍未明确。我们开展了首个直接比较这两种策略的系统评价与荟萃分析。检索了PubMed、Embase和Scopus自建库至2026年4月的数据。纳入标准为：前瞻性研究，入组接受新辅助ICI联合化疗或放化疗的非转移性可切除ESCC成年患者。采用随机效应模型分析汇总的病理完全缓解（pCR）率和主要病理缓解（MPR）率。共纳入53项前瞻性研究（2937例患者）。在主要分析中，巩固性ICI与同步ICI相比，pCR率显著更高（48% vs. 31%；= 0.0005）。然而，当限定于两组均使用放化疗的研究时，这一差异失去了统计学意义（48% vs. 41%；= 0.18），提示初始的优势在很大程度上归因于序贯治疗亚组中放化疗使用比例更高，而非ICI时机本身。MPR也观察到类似的模式。在治疗骨架匹配的情况下，同步与巩固ICI时机在可切除ESCC中产生的病理缓解率相当。有必要开展预先设定时机分组和生物标志物分层的随机试验。

Abstract

Immune checkpoint inhibitors (ICIs) are increasingly integrated into the neoadjuvant treatment of resectable esophageal squamous cell carcinoma (ESCC), yet the optimal timing of ICI administration remains undefined. We conducted the first systematic review and meta-analysis directly comparing these two strategies. PubMed, Embase, and Scopus were searched from inception through April 2026. Prospective studies enrolling adult patients with non-metastatic resectable ESCC who received neoadjuvant ICI alongside chemotherapy or chemoradiotherapy were eligible. Pooled pathological complete response (pCR) and major pathological response (MPR) were analyzed using random-effects models. Fifty-three prospective studies (2937 patients) were included. In the primary analysis, consolidation ICI was associated with significantly higher pCR than concurrent ICI (48% vs. 31%; = 0.0005). However, when restricted to studies using chemoradiotherapy in both arms, this difference lost statistical significance (48% vs. 41%; = 0.18), suggesting the initial advantage was largely attributable to a greater use of chemoradiotherapy in the sequential subgroup rather than ICI timing per se. A parallel pattern was observed for MPR. When matched for treatment backbone, concurrent and consolidation ICI timing produce comparable pathological response rates in resectable ESCC. Randomized trials with pre-specified timing arms and biomarker stratification are warranted.

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