引用文本：徐元亮, 熊文俊, 陈静, 等. 局部晚期直肠癌全程新辅助治疗联合免疫治疗的Meta分析[J/CD]. 消化肿瘤杂志（电子版）, 2026, 18(2): 264-274.

作者：徐元亮1，熊文俊2，陈静3，王伟2，张子敬2，李金2，陈妍2

单位：1. 广州中医药大学第一临床医学院，广东 广州 510405；2. 广州中医药大学第一附属医院胃肠外科，广东省中医临床研究院，广东 广州 510405；3. 广州中医药大学第一附属医院放射治疗科，广东省中医临床研究院，广东 广州 510405

Authors：Xu Yuanliang1, Xiong Wenjun2, Chen Jing3, Wang Wei2, Zhang Zijing2, Li Jin2, Chen Yan2

Unit：1. The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China；2. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405, Guangdong, China；3. Department of Radiation Oncology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510405, Guangdong, China

摘要：

目的 探讨全程新辅助治疗联合免疫治疗在局部晚期直肠癌中的疗效与安全性。方法 系统检索PubMed、EMBASE、Cochrane Library、ClinicalTrials.gov及中国知网数据库，筛选出2015年1月至2025年12月发表的全程新辅助治疗联合免疫治疗用于局部晚期直肠癌的随机对照试验文献。采用Cochrane偏倚风险评估工具评价纳入文献的质量，通过Review Manager 5.4.1软件进行Meta分析，主要结局指标为病理完全缓解率，其他结局指标包括临床完全缓解率、R0切除率、保肛率、3级及以上不良反应发生率，同时开展亚组分析[基于放射治疗（简称放疗）策略]、敏感性分析（逐一剔除法）及发表偏倚分析。结果 最终纳入7篇随机对照试验文献，共979例患者，其中试验组（全程新辅助治疗+免疫检查点抑制剂）528例，对照组（单纯全程新辅助治疗）451例。Meta分析结果显示，试验组病理完全缓解率（OR=2.27，95%CI 1.67~3.08，P<0.000 01）和R0切除率（OR=2.66，95%CI 1.42~4.97，P=0.002）均高于对照组；两组的临床完全缓解率（OR=1.90，95%CI 0.81~4.47，P=0.14）、保肛率（OR=1.49，95%CI 0.75~2.98，P=0.26）、3级及以上不良反应发生率（OR=1.35，95%CI 1.00~1.83，P=0.05）差异均无统计学意义。亚组分析和敏感性分析未发现临床完全缓解率的明确异质性来源，而保肛率的异质性主要来源于Rahma等的研究。此外，长程（OR=1.69，95%CI 1.12~2.56，P=0.01）与短程放疗（OR=2.77，95%CI 1.47~5.21，P=0.002）联合免疫检查点抑制剂均能提升病理完全缓解率。敏感性分析显示病理完全缓解率的合并结果稳定，发表偏倚分析提示无明显发表偏倚。结论 全程新辅助治疗联合免疫检查点抑制剂治疗局部晚期直肠癌可提高患者的病理完全缓解率和R0切除率，且不增加严重不良反应发生风险，安全性良好，但对临床完全缓解率和保肛率无明显改善；放疗策略不影响该联合方案的病理完全缓解率获益，临床可根据患者情况灵活选择。

关键词：直肠癌；全程新辅助治疗；免疫检查点抑制剂；Meta分析；病理完全缓解

Abstract：

Objective To explore the efficacy and safety of total neoadjuvant therapy (TNT) combined with immunotherapy for locally advanced rectal cancer (LARC). Method Randomized controlled trials (RCTs) on TNT combined with immunotherapy for LARC published from January 2015 to December 2025 were retrieved from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and China National Knowledge Infrastructure (CNKI) databases. The quality of included studies was evaluated using the Cochrane Risk of Bias tool, and Meta-analysis was performed using Review Manager 5.4.1 software. The primary outcome was pathological complete response (pCR) rate, while other outcomes included clinical complete response (cCR) rate, R0 resection rate, sphincter-preservation rate, and incidence of grade 3 or above adverse events. Subgroup analysis (according to radiotherapy regimens), sensitivity analysis (by leave-one-out method), and publication bias analysis were also conducted. Result A total of 7 RCTs involving 979 patients were finally included, with 528 patients in the experimental group (TNT plus immune checkpoint inhibitors) and 451 patients in the control group (TNT alone). Meta-analysis showed that the pCR rate (OR=2.27, 95%CI 1.67-3.08, P<0.000 01) and the R0 resection rate (OR=2.66, 95%CI 1.42-4.97, P=0.002) in the experimental group were higher than those in the control group. There were no statistically significant differences in the cCR rate (OR=1.90, 95%CI 0.81-4.47, P=0.14), the sphincter-preservation rate (OR=1.49, 95%CI 0.75-2.98, P=0.26), or the incidence of grade 3 or above adverse events (OR=1.35, 95%CI 1.00-1.83, P=0.05) between the two groups. Subgroup and sensitivity analyses identified no clear source of heterogeneity for the cCR rate, and the study by Rahma et al. was the main source of heterogeneity for the sphincter-preservation rate. Besides, both long-course (OR=1.69, 95%CI 1.12-2.56, P=0.01) and short-course (OR=2.77, 95%CI 1.47-5.21, P=0.002) radiotherapy combined with immune checkpoint inhibitors improved the pCR rate. Sensitivity analysis verified the stability of the combined pCR rate result, and publication bias analysis showed no obvious publication bias. Conclusion TNT combined with immune checkpoint inhibitors can improve the pCR rate and R0 resection rate in patients with LARC without increasing the risk of severe adverse events, demonstrating favorable safety. However, it has no significant improvement in cCR rate and sphincter-preservation rate. The radiotherapy course does not affect the pCR rate benefit of the combined regimen, and clinical selection can be flexibly made according to patients' conditions.

Key words：Rectal cancer; Total neoadjuvant therapy; Immune checkpoint inhibitors; Meta-analysis; Pathological complete response

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