Diagnostic Accuracy of Liquid Biomarkers for the Non-Invasive Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Abstract

Simple SummaryEndometrial cancer is common amongst women and rates are increasing annually. The diagnosis of this condition for women with bleeding after the menopause is invasive and often painful with many more women undergoing investigation than needed. A simple, non-invasive blood or urine test for the diagnosis of endometrial cancer is being sought. This review summarizes the current research on blood and urine tests and their diagnostic accuracy for detecting endometrial cancer. Whilst many blood and urine tests have been assessed there is currently no test that has a similar accuracy to biopsy of the uterine lining. However, this review demonstrates that there are some potential candidates which need to be explored by larger studies and on bigger groups of women. Endometrial cancer rates are increasing annually due to an aging population and rising rates of obesity. Currently there is no widely available, accurate, non-invasive test that can be used to triage women for diagnostic biopsy whilst safely reassuring healthy women without the need for invasive assessment. The aim of this systematic review and meta-analysis is to evaluate studies assessing blood and urine-based biomarkers as a replacement test for endometrial biopsy or as a triage test in symptomatic women. For each primary study, the diagnostic accuracy of different biomarkers was assessed by sensitivity, specificity, likelihood ratio and area under ROC curve. Forest plots of summary statistics were constructed for biomarkers which were assessed by multiple studies using data from a random-effect models. All but one study was of blood-based biomarkers. In total, 15 studies reported 29 different exosomal biomarkers; 34 studies reported 47 different proteomic biomarkers. Summary statistic meta-analysis was reported for micro-RNAs, cancer antigens, hormones, and other proteomic markers. Metabolites and circulating tumor materials were also summarized. For the majority of biomarkers, no meta-analysis was possible. There was a low number of small, heterogeneous studies for the majority of evaluated index tests. This may undermine the reliability of summary estimates from the meta-analyses. At present there is no liquid biopsy that is ready to be used as a replacement test for endometrial biopsy. However, to the best of our knowledge this is the first study to report and meta-analyze the diagnostic accuracy of different classes of blood and urine biomarkers for detection of endometrial cancer. This review may thus provide a reference guide for those wishing to explore candidate biomarkers for further research.