Supplementary Material for: Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis

Background: The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. Objectives: This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. Methods: The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Results: Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. Conclusions: In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura.背景：癌胚抗原（carcinoembryonic antigen, CEA）、糖类抗原（carbohydrate antigens, CA）125、15-3、19-9以及细胞角蛋白19片段（CYFRA 21-1）等肿瘤标志物联合检测在恶性胸腔积液（malignant pleural effusion, MPE）诊断中的作用尚未明确。 目的：本荟萃分析旨在明确上述胸腔积液肿瘤标志物联合检测用于恶性胸腔积液诊断的整体诊断效能。 方法：检索PubMed、Ovid、Embase、Web of Science及Cochrane图书馆数据库，对英文文献进行系统回顾后，汇总胸腔积液CEA、CA125、CA15-3、CA19-9及CYFRA 21-1联合检测诊断恶性胸腔积液的灵敏度、特异度及其他诊断效能指标。 结果：共计20项研究符合纳入标准。针对纳入研究数≥3项的胸腔积液肿瘤标志物联合检测方案，其诊断恶性胸腔积液的汇总灵敏度/特异度如下：CEA+CA125为0.65/0.98；CEA+CA15-3为0.64/0.98；CEA+CA19-9为0.58/0.98；CEA+CYFRA 21-1为0.82/0.92；CA15-3+CYFRA 21-1为0.88/0.94。 结论：对于未明确诊断的胸腔积液患者，胸腔积液CEA+CA15-3及CEA+CA19-9联合检测阳性高度提示胸膜恶性病变，但此类检测的灵敏度较差。因此，此类联合检测在该类患者诊断流程中的常规应用价值尚存争议，临床诊疗决策应基于胸膜细胞学或活检的阳性结果。