Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the management of several malignancies, including melanoma, non-small cell lung cancer, and urothelial carcinoma. However, these therapies frequently cause endocrine immune-related adverse events (irAEs), such as thyroid dysfunction, hypophysitis, or autoimmune diabetes, and may carry important prognostic implications. This systematic review and meta-analysis aimed to determine the incidence, spectrum, and clinical significance of endocrine irAEs across major tumor types. Methods: Following PRISMA guidelines and PROSPERO registration (CRD42025646504), we systematically searched PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus for studies reporting endocrine irAEs in ICI-treated patients. Random-effects meta-analyses estimated pooled hazard ratios (HRs) for overall (OS) and progression-free survival (PFS) and odds ratios (ORs) for adverse events. Subgroup and meta-regression analyses explored associations by cancer type, ICI class, and event severity. Results: Forty-three studies comprising 17,399 patients were included. Endocrine irAEs occurred in 11–30% of patients and were associated with improved OS (HR: 0.60, 95% CI: 0.54–0.67;p< 0.001) and PFS (HR: 0.61, 95% CI: 0.54–0.68;p< 0.001). Severe events were most frequent with pembrolizumab in melanoma and non-small cell lung cancer and with anti-programmed death-ligand 1 therapy in urothelial carcinoma. In exploratory meta-regression analyses accounting for cancer type, ICI subclass, and irAE severity, no statistically significant correlation was observed between the occurrence of endocrine irAEs (OR) and survival benefit (PFS HR: 0.20, 95% CI −0.10 to 0.51;p= 0.19; OS HR: 0.14,p> 0.05). Conclusions: The development of endocrine irAEs coincides with favorable long-term survival outcomes but may represent surrogate markers of immune activation rather than direct predictors of ICI efficacy. However, the lack of consistent ≥ 3-year follow-up across studies warrants cautious interpretation. Routine endocrine monitoring and interdisciplinary management are essential to optimize the safety and effectiveness of immunotherapy.
背景/目的：免疫检查点抑制剂（ICIs）已彻底改变了包括黑色素瘤、非小细胞肺癌和尿路上皮癌在内的多种恶性肿瘤的治疗模式。然而，此类疗法常引发内分泌免疫相关不良事件（irAEs），如甲状腺功能异常、垂体炎或自身免疫性糖尿病，并可能具有重要的预后意义。本系统综述与荟萃分析旨在明确主要肿瘤类型中内分泌irAEs的发生率、谱系及临床意义。方法：遵循PRISMA指南并在PROSPERO平台注册（CRD42025646504），我们系统检索了PubMed、Embase、Cochrane CENTRAL、Web of Science和Scopus数据库中报道ICI治疗患者内分泌irAEs的研究。采用随机效应模型进行荟萃分析，计算总生存期（OS）和无进展生存期（PFS）的合并风险比（HRs）以及不良事件的比值比（ORs）。通过亚组分析和荟萃回归分析探讨肿瘤类型、ICI类别及事件严重程度之间的关联。结果：共纳入43项研究，涉及17,399例患者。内分泌irAEs发生率为11–30%，且与OS（HR: 0.60, 95% CI: 0.54–0.67; p<0.001）和PFS（HR: 0.61, 95% CI: 0.54–0.68; p<0.001）改善相关。严重事件最常见于帕博利珠单抗治疗的黑色素瘤和非小细胞肺癌患者，以及抗程序性死亡配体1疗法治疗的尿路上皮癌患者。在考虑肿瘤类型、ICI亚类和irAE严重程度的探索性荟萃回归分析中，未观察到内分泌irAEs发生（OR）与生存获益之间存在统计学显著相关性（PFS HR: 0.20, 95% CI −0.10至0.51; p=0.19; OS HR: 0.14, p>0.05）。结论：内分泌irAEs的发生与良好的长期生存结局相关，但其可能作为免疫激活的替代标志物，而非ICI疗效的直接预测指标。然而，由于各研究缺乏一致的≥3年随访数据，需谨慎解读结果。常规内分泌监测及多学科协同管理对优化免疫治疗的安全性和有效性至关重要。
肿瘤(癌症)患者之家