Diagnostic value of clinical biomarkers (CA125, HE4) combined with MRI for lymph node metastasis in endometrial cancer: a meta-analysis

Accurate preoperative identification of lymph node metastasis (LNM) in endometrial cancer (EC) remains challenging. This systematic review and meta-analysis primarily aimed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) combined with serum carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) for identifying LNM in EC, while assessing the CA125+HE4 dual-marker strategy as a secondary analysis. PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, CQVIP, and SinoMed were systematically searched through March 2026. Eligible studies evaluated the diagnostic accuracy of MRI+CA125+HE4 and/or CA125+HE4 using postoperative histopathological assessment as the reference standard. Study quality was assessed using QUADAS-2, and diagnostic accuracy measures were synthesized separately for each strategy. Eleven studies involving 1,341 unique patients provided 13 diagnostic datasets. Four studies involving 418 patients evaluated the MRI+CA125+HE4 strategy, with a pooled sensitivity of 0.94 (95% CI: 0.87–0.98), specificity of 0.69 (95% CI: 0.52–0.82), and summary receiver operating characteristic curve area under the curve (SROC AUC) of 0.95 (95% CI: 0.92–0.96). Substantial heterogeneity was observed in specificity (I² = 92.17%). As a secondary analysis, nine studies evaluated the CA125+HE4 strategy, yielding a pooled sensitivity of 0.84 (95% CI: 0.76–0.90), specificity of 0.72 (95% CI: 0.60–0.78), and SROC AUC of 0.87 (95% CI: 0.84–0.90). The two strategies were analyzed separately without inferring comparative superiority. MRI combined with CA125 and HE4 showed promising diagnostic accuracy for identifying LNM in EC. However, the limited number of triple-test studies, substantial heterogeneity in specificity, and variations in diagnostic thresholds and positivity rules warrant cautious interpretation. The secondary CA125+HE4 analysis provides complementary evidence, while further prospective studies using standardized diagnostic criteria are needed to validate the clinical applicability of these findings. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261556800.