• 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.

      Jones, Eleanor R; Carter, Suzanne; O'Flynn, Helena; Njoku, Kelechi; Barr, Chloe E; Narine, Nadira; Shelton, David; Rana, Durgesh; Crosbie, Emma J; orcid: 0000-0003-0284-8630; email: emma.crosbie@manchester.ac.uk (2021-07-28)
      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 veloping ests for ndometrial ancer de ection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB. This is a multicentre 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 2000 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 urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women. This study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites. ISRCTN58863784. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
    • 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.

      Jones, Eleanor R; Carter, Suzanne; O'Flynn, Helena; Njoku, Kelechi; Barr, Chloe E; Narine, Nadira; Shelton, David; Rana, Durgesh; Crosbie, Emma J; orcid: 0000-0003-0284-8630; email: emma.crosbie@manchester.ac.uk (2021-07-28)
      <h4>Introduction</h4>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 <u>DE</u>veloping <u>T</u>ests for <u>E</u>ndometrial <u>C</u>ancer de<u>T</u>ection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB.<h4>Methods and analysis</h4>This is a multicentre 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 2000 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 urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women.<h4>Ethics and dissemination</h4>This study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites.<h4>Trial registration number</h4>ISRCTN58863784.
    • Synchronous uterine and bladder cancers detected in urine and vaginal samples by cytology

      Narine, Nadira; Rana, Durgesh; Shelton, David; Awad, Dina; O'Flynn, Helena; Jones, Eleanor R.; Ryan, Neil A. J.; Crosbie, Emma J.; orcid: 0000-0003-0284-8630; email: emma.crosbie@manchester.ac.uk (John Wiley & Sons, Inc., 2021-11-16)
      Abstract: Novel diagnostics for uterine cancer are urgently needed to reduce the burden of invasive testing for the majority of healthy women with postmenopausal bleeding. We have previously shown that uterine cancer cells can be detected by cytology in urine and vaginal samples with high diagnostic accuracy. Here, we demonstrate its potential to distinguish malignant cells of different aetiologies in the same urogenital biofluid sample according to their distinctive morphology and immunoprofiles. Synchronous tumours of the urogenital tract are uncommon but can cause diagnostic confusion, delays and poor outcomes. A 79‐year‐old woman presented to accident and emergency with postmenopausal bleeding. Voided urine and Delphi screener‐collected vaginal samples were assessed by cytology and immunocytochemistry. Two malignant cell populations with distinct morphology and immunophenotypes consistent with synchronous uterine and urothelial tumours were identified. Subsequent routine diagnostics confirmed concurrent uterine carcinosarcoma and high‐grade urothelial carcinoma of the bladder. This case demonstrates that cytology and adjunctive immunocytochemistry can simultaneously identify and phenotype cancers of different aetiologies from a single urogenital biofluid sample. This can help rationalise diagnostic pathways in complex, unusual cases of dual urogenital primaries.