Transforming endometrial cancer diagnosis: the case for molecular triage in abnormal uterine and post-menopausal bleeding.

Abnormal uterine bleeding is the most common symptom of endometrial cancer, but due to the low prevalence of underlying malignancy (3%), clinicians must distinguish those who can be quickly reassured from those who require urgent diagnosis and cancer treatment. The current diagnostic pathway is limited by the low specificity of transvaginal ultrasound, which leads to large numbers of invasive follow-up tests (hysteroscopy and biopsy). Transvaginal ultrasound may also miss almost a quarter of serous cancers, which have the poorest prognoses, and overall performance of this test, particularly specificity, is much lower in Black women. Many approaches have been explored to develop simple, objective, molecular triage tests, of which quantitative polymerase chain reaction-based DNA methylation tests in cervicovaginal samples have made significant progress. These data call on clinicians, researchers, and policymakers to invest in innovative diagnostic solutions and to reshape the diagnostic landscape for a cancer whose incidence and mortality continue to rise.