Endometrial Cancer
Endometrial cancer arises from the lining of the uterus and is the most common gynaecological cancer in developed countries. It has an unusual and fortunate characteristic among cancers: it usually announces itself early, through abnormal bleeding, at a stage when treatment is highly effective. Most women are diagnosed with disease still confined to the uterus, and outcomes at that stage are very good. That advantage depends entirely on bleeding being reported and investigated—particularly any bleeding after menopause, however slight. Incidence has been rising steadily, largely in parallel with obesity, which is the single most significant modifiable risk factor and the mechanism behind a substantial share of cases.
What is it?
The endometrium is the lining of the uterine cavity, a tissue that during reproductive years is rebuilt and shed with every menstrual cycle under hormonal control. Endometrial cancer arises when cells in this lining acquire genetic changes allowing uncontrolled growth and invasion into the underlying muscle.
The condition is sometimes called uterine cancer, though that term is broader: it also encompasses uterine sarcomas, which arise from the muscle or supporting tissue rather than the lining and are far less common, behave more aggressively, and are treated differently.
Endometrial cancer has traditionally been divided into two types based on appearance under the microscope and hormonal dependence.
Type 1 accounts for the large majority. These are endometrioid carcinomas, usually low grade, typically driven by oestrogen stimulation, often preceded by endometrial hyperplasia, and generally associated with a favourable outlook. They tend to occur in women with the classic risk profile of obesity and excess oestrogen exposure.
Type 2 is less common but accounts for a disproportionate share of deaths. These include serous carcinoma, clear cell carcinoma, and carcinosarcoma. They are not oestrogen-driven, occur in older and often thinner women, and behave more aggressively, spreading earlier and more widely.
This two-type framework remains useful but has been substantially refined by molecular classification, which has become one of the most significant developments in the field. Analysis of tumour DNA identifies four groups with strikingly different behaviour: tumours with POLE mutations, which have an excellent prognosis and may be safely undertreated relative to past practice; mismatch repair deficient tumours, which are intermediate in outlook and respond particularly well to immunotherapy; tumours with abnormal p53, which behave aggressively regardless of how they look under the microscope; and a remaining group with no specific molecular profile. These categories sometimes contradict the impression given by appearance alone, and they are now used to guide whether additional treatment after surgery is necessary. Molecular testing has become part of routine assessment rather than a research tool.
The dominant mechanism behind most endometrial cancer is unopposed oestrogen—oestrogen stimulating the lining without progesterone to balance it. Progesterone normally limits endometrial proliferation, and without it the lining is driven to grow continuously, accumulating genetic errors.
This explains the risk factors coherently.
Obesity is the most important modifiable factor and accounts for a substantial share of cases. Fat tissue converts circulating hormones into oestrogen, producing continuous low-level stimulation of the lining that persists long after the ovaries have stopped functioning. Risk rises steeply with increasing body weight, and this relationship is one of the strongest between obesity and any cancer.
Polycystic ovary syndrome causes infrequent ovulation and therefore infrequent progesterone exposure, leaving the lining under prolonged oestrogen influence.
Oestrogen-only hormone therapy in a woman who still has a uterus produces the same effect, which is why progestogen is always included unless the uterus has been removed.
Tamoxifen, used in breast cancer treatment, acts as an oestrogen blocker in breast tissue but has a stimulating effect on the endometrium, modestly increasing risk.
Diabetes, never having been pregnant, early first period, late menopause, and oestrogen-producing ovarian tumours all contribute. Increasing age is the strongest non-modifiable factor.
Lynch syndrome deserves separate emphasis. This inherited condition, caused by faults in DNA mismatch repair genes, carries a substantially elevated lifetime risk of endometrial cancer—comparable to or exceeding its risk of bowel cancer—along with risks of ovarian, colorectal, and other cancers. For many women with Lynch syndrome, endometrial cancer is the first cancer to appear, which makes recognising it an opportunity to prevent others. Tumour tissue is now routinely tested for features suggesting Lynch syndrome, and identifying it changes surveillance and has significant implications for relatives.
Certain factors reduce risk, and they operate through the same mechanism. Combined hormonal contraception substantially reduces risk, with protection persisting for many years after stopping. The levonorgestrel-releasing intrauterine system reduces risk. Pregnancy and breastfeeding reduce risk. Physical activity and maintaining a healthy weight are protective.
Symptoms are what makes this cancer distinctive among gynaecological malignancies.
Abnormal bleeding is the presenting symptom in the great majority of cases, and it tends to occur early—often while disease is still confined to the uterus. This is fundamentally different from ovarian cancer, which produces vague symptoms and is usually advanced at diagnosis, and it is the reason endometrial cancer has generally good outcomes despite there being no screening programme.
After menopause, the rule is simple and absolute: any bleeding warrants investigation. This includes a single episode, light spotting, pink or brown discharge, staining noticed only on wiping, and bleeding a woman assumes must come from elsewhere. Most women investigated will have a benign explanation—atrophic changes are the most common—but the only way to establish that is to check.
Before menopause, the picture is harder, because abnormal bleeding is common and usually benign. Patterns warranting assessment include bleeding between periods, bleeding after intercourse, a clear change to markedly heavier or longer periods, and persistently irregular cycles—particularly in women with obesity, polycystic ovary syndrome, diabetes, or a family history suggesting Lynch syndrome. Younger women with these risk factors are the group in whom diagnosis is most often delayed, because symptoms are attributed to hormonal irregularity.
Persistent watery or blood-tinged discharge can occur, sometimes before frank bleeding. Pelvic pain, pressure, abdominal swelling, weight loss, and urinary or bowel symptoms tend to indicate more advanced disease.
Diagnosis and staging follow a defined pathway.
Transvaginal ultrasound is usually the first test. In a postmenopausal woman with bleeding, an endometrial thickness at or below approximately 4 millimetres makes cancer very unlikely, while a thicker lining prompts sampling. This threshold applies specifically to postmenopausal women who are bleeding. Persistent or recurrent bleeding warrants further investigation regardless of the measurement.
Endometrial biopsy provides tissue diagnosis and can usually be taken in clinic using a fine suction device, without anaesthetic. Its main limitation is that it samples blindly and can miss a focal lesion, so a normal result in a woman with continuing symptoms does not close the matter.
Hysteroscopy allows the cavity to be inspected directly and a targeted biopsy taken, and is used when biopsy is inconclusive or non-diagnostic, when bleeding persists, or when a focal lesion is suspected. It is frequently performed as an outpatient procedure.
MRI of the pelvis is the key staging investigation, defining how deeply the cancer has invaded the muscular wall, whether it involves the cervix, and whether lymph nodes are enlarged. Depth of invasion is one of the strongest predictors of nodal spread and directly influences surgical planning.
CT of the chest, abdomen, and pelvis assesses spread beyond the pelvis, and PET-CT is used in selected situations.
Molecular and mismatch repair testing of the tumour is now routine, informing both treatment decisions and the identification of Lynch syndrome.
Staging is surgical, based on what is found at operation and on examination of the removed tissue, and incorporates depth of muscle invasion, cervical involvement, spread to ovaries or other structures, lymph node status, and increasingly molecular features.
Important to Know
The central practical message is that endometrial cancer is usually curable when found early, and that finding it early depends on abnormal bleeding being reported and investigated rather than waited out. Care is coordinated by gynaecological oncology teams, with input from radiology, pathology, medical and radiation oncology, genetics, and specialist nursing.
Most women are diagnosed with disease confined to the uterus, and survival at that stage is high—commonly cited five-year survival for early-stage disease exceeds 90%. This is a genuinely favourable position relative to most cancers, and it is worth stating plainly to women facing the diagnosis, who often assume the worst on hearing the word.
Surgery is the primary treatment and for most women is curative on its own. It involves removal of the uterus, cervix, fallopian tubes, and ovaries. A minimally invasive approach—laparoscopic or robotic—is standard for early-stage disease, with equivalent cancer outcomes to open surgery alongside less pain, shorter hospital stay, and faster recovery. Lymph node assessment is guided by risk, and sentinel node mapping—identifying and removing only the first draining nodes—has largely replaced full pelvic lymph node dissection in appropriate cases, substantially reducing the risk of lymphoedema while providing the same staging information.
Removal of the ovaries in premenopausal women causes immediate surgical menopause, and this is an important conversation before surgery. In carefully selected young women with early low-grade disease, ovarian preservation may be considered.
Additional treatment after surgery depends on the risk of recurrence. Vaginal brachytherapy—radiotherapy delivered internally to the top of the vagina—is commonly used for intermediate-risk disease and is well tolerated. External beam pelvic radiotherapy and chemotherapy are used for higher-risk disease. Molecular classification now informs these decisions directly: some tumours previously treated aggressively based on appearance are now recognised as low risk, while others that looked reassuring are known to behave aggressively and are treated accordingly.
Advanced and recurrent disease has seen substantial change. Immunotherapy has become an important option, particularly effective in mismatch repair deficient tumours, and combination approaches with targeted therapy have improved outcomes in several settings. Hormonal therapy with progestogens is effective in some low-grade oestrogen-driven cancers. This is a rapidly evolving area, and asking about current options and clinical trials is worthwhile.
Fertility-sparing treatment is possible for a carefully selected group—young women with early-stage, low-grade endometrioid cancer confined to the lining without evidence of muscle invasion. Treatment uses high-dose progestogen, often delivered by intrauterine system, with close surveillance and repeated sampling. It requires specialist assessment, careful counselling about the risks involved, and a plan for definitive surgery once childbearing is complete. It is an option rather than an expectation, and not all women are suitable.
Weight and metabolic health deserve direct attention rather than being treated as background. Obesity contributes to developing this cancer, complicates surgery, increases the risk of complications, and is associated with poorer outcomes and higher risk of recurrence and of other diseases. Support for weight management after treatment is a legitimate and valuable part of care, and where relevant, bariatric surgery has been shown to reduce endometrial cancer risk substantially.
Genetic assessment matters. All endometrial cancers are now routinely tested for mismatch repair abnormalities, and women whose tumours show relevant features are referred for genetic counselling. Identifying Lynch syndrome allows targeted surveillance for bowel and other cancers and enables testing of relatives, for whom the information can be preventive.
Follow-up after treatment involves clinical review, with attention to symptoms—particularly vaginal bleeding, which is the most common sign of recurrence—rather than routine intensive imaging in most protocols. Women are advised on what to look for and encouraged to report symptoms between appointments rather than waiting.
Managing the effects of treatment matters alongside cancer control. Surgical menopause in younger women warrants discussion of hormone therapy, which can be appropriate in selected low-risk cases. Lymphoedema, sexual function, vaginal changes after radiotherapy, and psychological impact are all legitimate concerns deserving active management rather than acceptance.
Care is coordinated by gynaecological oncology, and treatment at centres with specific expertise is associated with better outcomes. Imaging, pathology, molecular findings, and clinical assessment are interpreted together alongside a woman’s age, health, and priorities.
Patient education plays an important role. Understanding that postmenopausal bleeding always warrants investigation, that most cases are found early and are curable, that surgery alone suffices for many women, that molecular testing now refines who needs additional treatment, that fertility-sparing options exist for a small selected group, and that recurrence most often signals itself through bleeding all contribute to appropriate care.
Red flag symptoms include any vaginal bleeding after menopause, including a single episode of spotting or pink or brown discharge; bleeding between periods or after intercourse; periods that have become markedly heavier, longer, or irregular, particularly with risk factors present; persistent watery or blood-stained vaginal discharge; new pelvic pain or pressure; abdominal swelling; unexplained weight loss; new leg swelling; difficulty passing urine or a change in bowel habit; and, after treatment for endometrial cancer, any new vaginal bleeding or discharge. These warrant prompt medical evaluation.