Urine CA125 and HE4 for the Triage of Symptomatic Women with Suspected Endometrial Cancer

Simple Summary Women with suspected endometrial cancer undergo investigations that can be painful and anxiety-provoking. These tests are avoidable, as only 5-10% of symptomatic women have underlying cancer. A simple and accurate urine-based test to triage symptomatic women in the community will improve patient care. In this study, we evaluated the performance of two proteins (CA125 and HE4) for the detection of endometrial cancer in urine samples of 153 symptomatic women. We discovered that both proteins were significantly elevated in the urine of women with cancer compared to those without cancer. Urine CA125 performed better than HE4 in detecting endometrial cancer. When we combined urine CA125 and endometrial thickness measurement by transvaginal ultrasound scan, there was improvement in the detection of endometrial cancer. This is the first study to evaluate the performance of these proteins in urine for endometrial cancer detection. Confirmation in a larger sample is needed. A simple, noninvasive and accurate detection tool that can triage women with suspected endometrial cancer for definitive testing will transform patient care. The aim of this study was to evaluate urine CA125 and HE4 levels for the detection of endometrial cancer in symptomatic women. This was a cross-sectional diagnostic accuracy study of 153 symptomatic women who underwent urgent diagnostic investigations for suspected endometrial cancer at a large gynecological cancer center. Urine samples were collected prior to routine clinical procedures. Urine CA125 and HE4 levels were determined using automated chemiluminescent enzyme immunoassays. Univariate and multivariable receiver operating characteristic (ROC) curve analyses were performed. Urine CA125 and HE4 were discovered to be significantly elevated in women with endometrial cancer, compared to controls (p < 0.001 and p = 0.01, respectively). Urine CA125 and HE4 detected endometrial cancer with an area under the ROC curve (AUC) of 0.89 (0.81, 0.98) and 0.69 (0.55, 0.83), respectively. CA125 exhibited good discriminatory potential for Type I and early-stage tumors (AUC 0.93 and 0.90, respectively). A diagnostic model that combined urine CA125 and transvaginal ultrasound-measured endometrial thickness predicted endometrial cancer with an AUC of 0.96 (0.91, 1.00). Urine CA125 displays potential as a diagnostic tool for symptomatic women with suspected endometrial cancer. When combined with transvaginal ultrasound-measured endometrial thickness, this patient-friendly, urine-based test could help triage women for invasive diagnostics or safe reassurance, reducing costs and improving patient experience.