Multicenter evaluation of blood‐based biomarkers for the detection of endometriosis and adenomyosis: A prospective non‐interventional study
Stefanie Burghaus, Predrag Drazic, Monika Wölfler, Sylvia Mechsner, Magdalena Zeppernick, Ivo Meinhold‐Heerlein, Michael D. Mueller, Ralf Rothmund, Paola Viganò, Christian M. Becker, Krina T. Zondervan, Matthias W. Beckmann, Peter A. Fasching, Sibylle Berner‐Gatz, Felix S. Grünewald, Martin Hund, Peter Kastner, Martin Klammer, Ruediger P. Laubender, Heike Wegmeyer, Ursula‐Henrike Wienhues‐Thelen, Stefan P. Renner
Abstract
OBJECTIVE: To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS: This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS: CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION: This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.