DEveloping Tests for Endometrial Cancer deTection (DETECT): Protocol for a diagnostic accuracy study of urine and vaginal samples for the detection of endometrial cancer by cytology in women with postmenopausal bleeding

Introduction: Postmenopausal bleeding (PMB), the red flag symptom for endometrial cancer, triggers urgent investigation by transvaginal ultrasound scan, hysteroscopy and/or endometrial biopsy. These investigations are costly, invasive and often painful or distressing for women. In a pilot study, we found that voided urine and non-invasive vaginal samples from women with endometrial cancer contain malignant cells that can be identified by cytology. The aim of the DETECT study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB.

Methods and analysis: This is a multi-centre diagnostic accuracy study of women referred to secondary care with PMB. Eligible women will be asked to provide a self-collected voided urine sample and a vaginal sample collected with a Delphi screener before routine clinical procedures. Pairs of specialist cytologists, blinded to participant cancer status, will assess and classify samples independently, with differences settled by consensus review or involving a third cytologist. Results will be compared with clinical outcomes from standard diagnostic tests. A sample size of 2,000 women will have 80% power to establish a sensitivity of vaginal samples for endometrial cancer detection by cytology of ≥85% ±7%, assuming 5% endometrial cancer prevalence. The primary objective is to determine the diagnostic accuracy of vaginal samples for endometrial cancer detection by cytology. Secondary objectives include the diagnostic accuracy of urine and combined urogenital cytology, and the acceptability of urine and vaginal sampling to women.