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

Abstract

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.

Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features

“…No studies have evaluated the serum markers in combination with endometrial thickness for endometrial cancer detection; however, urine CA125 and HE4 in combination with ET has been investigated, with a reported improvement in AUC with the addition of urine CA125 to ET compared with ET alone (AUC 0.97 vs. 0.94, respectively) [ 33 ].…”

HE4 Tissue Expression as A Putative Prognostic Marker in Low-Risk/Low-Grade Endometrioid Endometrial Cancer: A Review

“…In 2022, Njoku et al [ 72 ] for the first time focused on the diagnostic accuracy of urine CA125 and HE4 levels for the triage of women with postmenopausal abnormal uterine bleeding. Overall, 153 women participated in the study and they were divided into two cohorts.…”

“…The discovery cohort included 61 women (30 endometrial cancer cases and 31 controls). The validation cohort included 92 (33 cases and 59 controls) [ 72 ]. Urine samples were collected prior to any clinical procedures.…”

“…Urine CA125 predicted endometrial cancer with a sensitivity of 72% while HE4 sensitivity was 32%. The small sample size and the lack of data on the molecular classification of endometrial cancer are the two limitations of this study [ 72 ].…”

Advances on Prevention and Screening of Gynecologic Tumors: Are We Stepping Forward?

“…TVS screening for endometrial cancer has good sensitivity in postmenopausal women, as shown by a case–control study within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) cohort [ 20 ]. Recent studies have shown that urine CA125 displays potential as a diagnostic marker for symptomatic women with suspected endometrial cancer [ 21 ], but more robust molecular markers are still to be implemented in the clinical practice [ 22 ].…”