Endometrial Cancer is malignant disease arising from the endometrium, the inner lining of the uterus. It is the most common type of uterine cancer and is predominantly composed of endometrioid adenocarcinoma, although other histological subtypes exist and can behave more aggressively. The disease is biologically heterogeneous, and modern classification increasingly incorporates molecular characteristics alongside traditional histopathology. Endometrial Cancer often presents with abnormal uterine bleeding at an early stage, which can facilitate diagnosis before extensive spread. It is distinct from cervical cancer, which arises from the cervix, and from uterine sarcomas, which originate from connective or muscular tissues and have different biology and treatment considerations.
A major risk factor is prolonged exposure to oestrogen without adequate opposing progesterone effect on the endometrium. Obesity can increase endogenous oestrogen exposure through peripheral conversion of androgens in adipose tissue and is strongly associated with risk. Other factors include older age, diabetes, metabolic disorders, certain reproductive histories and some forms of hormone therapy. Tamoxifen can increase endometrial cancer risk because of its effects on the uterine endometrium. Lynch syndrome substantially increases the risk of Endometrial Cancer and is an important inherited cause, particularly when cancer occurs at a younger age or alongside a suggestive family history. Risk therefore reflects hormonal, metabolic, reproductive and genetic factors.
Abnormal vaginal bleeding is the characteristic presenting feature, especially bleeding after menopause. Premenopausal patients may experience unusually heavy, prolonged or irregular menstrual bleeding. Pelvic discomfort, abnormal discharge or an enlarged uterus can occur but are less specific. Because postmenopausal bleeding can be an early sign of endometrial malignancy, it requires appropriate evaluation rather than being assumed to represent benign hormonal changes. The presence of bleeding does not establish cancer because polyps, endometrial atrophy and other conditions can cause similar symptoms, but persistent or postmenopausal bleeding warrants investigation.
Diagnosis generally involves assessment of the endometrium using endometrial biopsy, hysteroscopy or related sampling techniques. Transvaginal ultrasound can evaluate endometrial thickness and uterine structures, but tissue diagnosis is required to establish malignancy. Histology identifies the tumour type and grade, while staging determines the extent of disease. Modern molecular classification can identify categories such as mismatch-repair-deficient tumours, POLE-mutated tumours, p53-abnormal tumours and other molecular groups with prognostic and therapeutic relevance. This approach reflects a shift from treating all endometrial adenocarcinomas as biologically equivalent toward more precise risk classification.
Treatment for many localised Endometrial Cancer cases centres on hysterectomy, usually with removal of the fallopian tubes and ovaries, with the extent of lymph-node assessment determined by risk and disease characteristics. Minimally invasive surgery is commonly used when appropriate. Adjuvant radiotherapy or systemic therapy may be recommended for patients with higher-risk features to reduce recurrence risk. Fertility-sparing treatment can be considered in carefully selected younger patients with low-grade, hormone-responsive, uterine-confined disease who understand the need for close surveillance and the limitations of conservative treatment. Such management is specialised and not appropriate for every histological or molecular subtype.
Advanced or recurrent Endometrial Cancer can require systemic treatment. Hormone therapy may be useful for selected hormone-receptor-positive tumours, while chemotherapy has an important role in higher-risk or advanced disease. Immune checkpoint inhibitors have become important, particularly for tumours with mismatch-repair deficiency or microsatellite instability, and are also used in other selected advanced settings. Molecular classification increasingly helps determine prognosis and treatment selection. Abnormal p53 signalling, POLE mutations and mismatch-repair status can divide tumours into biologically distinct groups with different expected behaviour and responses to treatment.
Endometrial Cancer differs biologically from cervical cancer because its principal causal and risk pathways are not centred on persistent high-risk HPV infection. It also differs from ovarian cancer because the primary site is the uterine lining, although advanced disease can involve ovaries, fallopian tubes or other pelvic structures. Lynch syndrome is particularly important because endometrial cancer can be an early manifestation of inherited mismatch-repair deficiency. Obesity-related metabolic dysfunction is another major population-level risk factor, making prevention research closely connected with weight, metabolic health and hormonal exposure. Nevertheless, risk factors do not determine individual outcomes, and Endometrial Cancer can occur in people without obvious risk factors.
Prognosis is generally favourable when Endometrial Cancer is diagnosed while confined to the uterus, but outcomes vary substantially by stage, histology, grade and molecular subtype. There is no equivalent population screening programme for average-risk asymptomatic women because routine testing has not demonstrated sufficient benefit. Prompt evaluation of abnormal uterine bleeding is therefore central to early detection.
A common misconception is that Endometrial Cancer occurs only after menopause; although risk increases with age, younger people can develop it, particularly in the presence of inherited or hormonal risk factors. Advances in molecular classification, minimally invasive surgery, radiotherapy, systemic treatment and immunotherapy continue to refine management and allow treatment intensity to be better matched to tumour biology and recurrence risk.
