Endometrial cancer incidence is increasing worldwide, placing strain on diagnostic pathways for women presenting with abnormal uterine bleeding. Current assessment relies on transvaginal ultrasound (TVUS) followed by invasive endometrial visualisation and sampling, although most symptomatic women do not have malignant disease. Urine is an appealing non-invasive and repeatable biofluid that can capture tumour-associated material by both systemic renal filtration and local shedding from the uterus. Recent work has evaluated multiple urinary biomarkers for endometrial cancer detection, including somatic mutations, DNA methylation markers, proteins and peptides, vibrational spectroscopy signatures, microRNAs, metabolites and urine cytology. Collectively these assays map to biological processes implicated in endometrial carcinogenesis such as hormonal and metabolic alterations, immune activation, epithelial–stromal disruption, cellular proliferation and genomic instability. Some DNA methylation panels and mutation-based assays have reported sensitivities and specificities exceeding 80–90% in symptomatic populations. Proteomic, metabolomic and spectroscopy-based approaches remain promising but require greater standardisation and prospective validation. While not yet appropriate for population screening, urinary biomarkers could support risk stratification and triage to reduce unnecessary invasive investigations. Successful clinical implementation will need standardised protocols, multi-centre validation and incorporation into existing diagnostic pathways.
Endometrial cancer is among the most common malignancies affecting women globally. The source reports over 420,000 new cases and roughly 98,000 deaths in 2022. The global age-standardised incidence rate was estimated at 8.4 per 100,000 women, with substantial geographic variation. In the UK, incidence has risen markedly over recent decades; cases increased by 59% between 1993 and 2018, with more than 10,000 diagnoses annually. The rising burden is closely linked to demographic ageing and increasing prevalence of obesity. Obesity-related mechanisms cited include excess oestrogen exposure, hyperinsulinaemia and chronic inflammation, which together contribute substantially to endometrial carcinogenesis. Other established risk factors include polycystic ovary syndrome, diabetes, nulliparity, hypertension, tamoxifen exposure and genetic predisposition such as Lynch syndrome. Molecular subtypes (POLE-mutant, MMR deficient, copy-number low, and copy-number high/p53 abnormal) inform prognosis and treatment.
In the UK, TVUS is the first-line imaging test for women with abnormal uterine bleeding. TVUS is minimally invasive, avoids ionising radiation and allows measurement of endometrial thickness. Women with concerning imaging findings usually proceed to endometrial visualisation and sampling, which is invasive and resource intensive. Most symptomatic women ultimately have benign pathology, so there is clinical need for better triage tools to target invasive diagnostics to those at higher risk.
Urine offers practical advantages: it is non-invasive, easily collected and repeatable. Tumour-associated signals may be present in urine through two principal routes: systemic release of DNA, proteins and metabolites that are filtered or concentrated by the kidneys, and local shedding of uterine cells or molecular material that can reach urine. The combination of these routes allows urine to potentially reflect multiple aspects of tumour biology. These features make urine an attractive medium for developing triage tests for symptomatic women and for longitudinal monitoring, provided assays are sufficiently sensitive and specific.
The review summarises multiple classes of candidate urinary biomarkers:
Somatic mutation assays detecting tumour-specific DNA alterations.
DNA methylation panels targeting cancer-associated epigenetic changes.
Proteomic and peptide signatures identified by mass spectrometry or targeted assays.
Vibrational spectroscopy signatures that capture molecular composition patterns.
MicroRNAs and other small non-coding RNAs measured in urine.
Metabolomic profiles reflecting altered tumour and host metabolism.
Urine cytology assessing shed urogynecological cells for malignant features.
Each class maps to biological processes relevant to endometrial cancer, such as genomic instability, proliferative signalling, metabolic dysregulation and immune-related changes.
According to the source, DNA methylation panels and mutation-based urine assays have shown encouraging diagnostic performance in symptomatic cohorts, with some studies reporting sensitivities and specificities in the range of 80–90% or greater. Urine cytology also demonstrates diagnostic potential in selected cohorts. The review notes that metabolomic, proteomic and spectroscopy methods are promising but currently require further standardisation and prospective validation. The source does not provide exhaustive lists of individual assay names, study sizes or cohort characteristics in the provided sections; those details were not reported in the supplied excerpt.
Key barriers to implementation include variability in pre-analytical handling (collection, storage, processing), lack of standardised assay pipelines, heterogeneity in study designs and cohorts, and limited prospective multi-centre validation. Many candidate markers have been evaluated in single-centre or retrospective studies; reproducibility across laboratories and populations remains to be established. Integration into existing diagnostic pathways will demand evidence that urinary tests safely reduce invasive procedures without missing clinically significant disease.
The review highlights potential near-term applications of urinary biomarkers for triage of symptomatic women presenting with abnormal uterine bleeding. Well-validated urine tests could help prioritise women for TVUS and endometrial sampling, reduce unnecessary invasive investigations, and possibly support longitudinal monitoring in selected patients. The authors indicate that urinary biomarkers are not yet ready for population screening.
To advance clinical translation, the review calls for standardised pre-analytical protocols, harmonised assay platforms, larger prospective multi-centre validation studies and assessment of clinical utility within existing diagnostic pathways. Ultimately, urinary biomarkers show considerable promise as a non-invasive tool to detect endometrial cancer and to improve triage of symptomatic women, but evidence gaps remain and further rigorous validation is required before routine clinical adoption.