What Is Endometrial Cancer?
Endometrial cancer is a malignant tumor that develops in the endometrium — the inner lining of the uterus (womb). It is the most common cancer of the female reproductive organs in high-income countries and ranks among the most frequently diagnosed cancers in women worldwide.
The uterus is a hollow, pear-shaped muscular organ where a pregnancy develops. It consists of three layers:
- Endometrium – the inner lining, which thickens and sheds each month during the menstrual cycle under the influence of hormones (estrogen and progesterone)
- Myometrium – the middle muscular layer
- Serosa (perimetrium) – the thin outer covering
Each month, estrogen stimulates the endometrium to grow in preparation for a possible pregnancy, while progesterone matures and stabilizes it. When pregnancy does not occur, hormone levels fall and the lining is shed as menstrual bleeding. When this delicate hormonal balance is disturbed — particularly when estrogen acts without sufficient progesterone to oppose it — the cells of the endometrium can multiply excessively and, over time, transform into cancer.
How Common Is It?
- Globally, approximately 420,000 new cases are diagnosed each year, and the incidence is rising, largely due to increasing rates of obesity and aging populations.
- It typically affects postmenopausal women, with the average age at diagnosis being around 60–63 years.
- About 75% of cases are diagnosed at an early stage (confined to the uterus), mainly because the disease produces a clear and early warning sign — abnormal vaginal bleeding.
- Although more common in white women, women of African ethnicity are more likely to be diagnosed at a later stage and with more aggressive tumor subtypes.
Because around 90% of women with endometrial cancer experience abnormal vaginal bleeding, most tumors are caught early — which is one of the reasons it generally has a favorable prognosis compared with other gynecological cancers.
Types of Endometrial Cancer
Doctors have traditionally divided endometrial cancer into two broad categories based on how the tumor develops and behaves.
Type 1 (Estrogen-Dependent) – About 80% of Cases
These tumors are driven by prolonged, “unopposed” estrogen stimulation of the endometrium. They usually develop slowly, passing through a precancerous stage called atypical hyperplasia (endometrial intraepithelial neoplasia), and are generally low-grade with a good prognosis. The most common form is endometrioid adenocarcinoma.
Type 2 (Non-Estrogen-Dependent) – About 10–20% of Cases
These tumors are not linked to estrogen excess. They tend to arise in older women, often within a thin, atrophic endometrium, and are more aggressive, with a higher likelihood of spreading beyond the uterus. Examples include serous carcinoma, clear cell carcinoma, and carcinosarcoma.
Table 1. Comparison of Type 1 and Type 2 endometrial cancers
| Feature | Type 1 | Type 2 |
|---|---|---|
| Proportion of cases | ~80% | ~10–20% |
| Hormone dependence | Estrogen-driven | Not estrogen-driven |
| Typical patient | Younger, often with obesity or metabolic disorders | Older, often with thin/atrophic endometrium |
| Precursor lesion | Atypical hyperplasia | Serous endometrial intraepithelial carcinoma |
| Grade | Usually low-grade (1–2) | High-grade (3) |
| Genetic profile | PTEN, KRAS, PIK3CA mutations; microsatellite instability | TP53, HER2 mutations |
| Prognosis | Generally favorable | More aggressive, poorer outcome |
Histological Subtypes
Table 2. Main microscopic (histological) types of endometrial cancer
| Subtype | Approx. frequency | Behavior |
|---|---|---|
| Endometrioid adenocarcinoma | 75–80% | Usually low-grade, favorable prognosis |
| Serous carcinoma | 5–10% | High-grade, aggressive, spreads early |
| Clear cell carcinoma | 2–5% | High-grade, aggressive |
| Carcinosarcoma | ~5% | Contains both gland and connective tissue components; very aggressive |
| Mucinous carcinoma | ~1–2% | Generally behaves like endometrioid type |
| Undifferentiated/dedifferentiated | ~2% | Poorly defined, aggressive |
| Neuroendocrine, mixed, other rare types | <2% | Variable, often aggressive |
In recent years, molecular (genetic) testing has added a four-group molecular classification that helps predict behavior more precisely: POLE-ultramutated (excellent prognosis), mismatch-repair deficient/dMMR (intermediate, often linked to Lynch syndrome and responsive to immunotherapy), p53-abnormal (aggressive), and no specific molecular profile (NSMP).
Causes and Risk Factors
The exact cause of endometrial cancer is not fully understood, but scientists agree that long-term unopposed estrogen exposure and metabolic disturbances play a central role in most cases. Anything that increases the lifetime exposure of the endometrium to estrogen without the balancing effect of progesterone raises the risk.
Table 3. Major risk factors
| Risk factor | Approximate increase in risk | Explanation |
|---|---|---|
| Obesity | 2–4× higher | Fat tissue converts other hormones into estrogen |
| Estrogen-only hormone therapy (without progestin) | 2–10× (depends on duration) | Unopposed estrogen stimulates the lining |
| Tamoxifen (breast cancer drug) | 2–3× | Acts like estrogen on the uterus |
| Never having given birth (nulliparity) | up to 2–3× | More lifetime ovulatory cycles |
| Early first period / late menopause | ~2× | Longer total estrogen exposure |
| Diabetes and metabolic syndrome | ~2× | Insulin resistance and hormonal effects |
| Lynch syndrome (hereditary) | Lifetime risk up to 40–60% | Inherited DNA-repair gene defect |
| PCOS (polycystic ovary syndrome) | 2–3× | Chronic lack of ovulation → unopposed estrogen |
| Age over 50 | Risk rises steadily with age | Most cases occur after menopause |
| Previous pelvic radiation | Moderately increased | Cellular damage to uterine tissues |
| Estrogen-producing ovarian tumors | Increased | Continuous estrogen secretion |
| Family history of endometrial or bowel cancer | Increased | May indicate an inherited syndrome |
Protective Factors (Lower the Risk)
- Pregnancy and childbirth — progesterone predominates during pregnancy, giving the endometrium a “rest”
- Combined oral contraceptives — can reduce risk by up to 30–50%, with protection lasting years after stopping
- Breastfeeding
- Regular physical activity and maintaining a healthy body weight
- Progestin-containing intrauterine devices (IUDs), such as the levonorgestrel IUD
How Does It Look?
Understanding what endometrial cancer looks like — both to the naked eye and under the microscope — helps explain how it grows and why it behaves the way it does.
Macroscopic (Gross) Appearance — What the Eye Can See
When the uterus is examined (for example, after surgical removal), endometrial cancer typically appears in one of two growth patterns:
- Localized (polypoid/exophytic) form: The tumor grows as a single, mushroom- or cauliflower-like mass projecting from the wall into the uterine cavity. It may be attached by a broad or narrow stalk, similar to a polyp.
- Diffuse form: The tumor spreads broadly across the surface of the endometrium, involving large areas or even the entire lining, without forming a single distinct mass.
Typical visual characteristics include:
- Color: greyish-white to yellowish-tan, often distinguishable from the surrounding pinkish-tan normal tissue
- Texture: soft, fragile, friable (easily crumbled or broken), because tumor tissue lacks the structural support of healthy lining
- Surface changes: areas of bleeding (hemorrhage) and tissue death (necrosis) are common, giving the surface an uneven, ulcerated, or crusted appearance; these fragile areas are the source of the abnormal bleeding that characterizes the disease
- Uterine enlargement: in advanced tumors, the mass can fill and expand the uterine cavity, enlarging the whole uterus
- Invasion: as the tumor grows deeper, pale, yellow-white streaks or zones may be visible extending into the muscular wall (myometrium); in advanced disease the growth may reach the cervix, or even extend through the uterine wall toward the bladder, bowel, or abdominal cavity
Interestingly, aggressive (Type 2) cancers, such as serous carcinoma, may arise in a small, atrophic uterus, sometimes originating within a single small polyp — their behavior is dangerous despite an unimpressive appearance.
Microscopic Appearance — What the Pathologist Sees
Under the microscope, the appearance depends on the subtype:
- Endometrioid adenocarcinoma (most common): Abnormal glands that resemble (poorly organized versions of) normal endometrial glands. They are overcrowded, irregular in shape, and packed “back-to-back” with almost no supporting tissue (stroma) between them. The lining cells are enlarged, elongated, darker-staining, and show abnormal, disordered nuclei that pile on top of each other. Some tumors contain areas of squamous cells or branching villous (finger-like) structures.
- Serous carcinoma: Complex papillary (branching, finger-like) structures lined by markedly abnormal cells, sometimes with round, sand-like calcium deposits called psammoma bodies.
- Clear cell carcinoma: Cells with transparent (clear) cytoplasm, sometimes with the nucleus protruding into the gland space (“hobnail” cells).
- Carcinosarcoma: A mixture of malignant glandular tissue and malignant connective-tissue (sarcomatous) elements.
Pathologists also assign a grade to endometrioid tumors, based on how much of the tumor forms recognisable glands versus solid sheets of cells:
- Grade 1 (well differentiated): 5% or less solid growth — cells look close to normal
- Grade 2 (moderately differentiated): 6–50% solid growth
- Grade 3 (poorly differentiated): more than 50% solid growth — cells look highly abnormal and behave aggressively
How It Looks on Medical Imaging and Endoscopy
- Transvaginal ultrasound: the endometrium appears abnormally thickened, irregular, or heterogeneous, sometimes with a visible mass or altered blood flow on Doppler imaging
- Hysteroscopy (a camera inserted through the cervix into the uterus): the tumor may appear as an irregular, fleshy, polyp-like, or cauliflower-shaped mass, often with fragile surface vessels that bleed easily when touched, together with discoloration or necrotic areas
- MRI/CT scans: used after diagnosis to see how deeply the tumor invades the muscle wall and whether it has spread to nearby organs or lymph nodes
Symptoms
The hallmark of endometrial cancer is abnormal vaginal bleeding, which occurs in approximately 90% of patients. Because this warning sign appears while the disease is still at an early stage, many women are diagnosed when the cancer is highly curable. Any unusual bleeding — especially after menopause — must always be investigated.
The Cardinal Symptom: Postmenopausal Bleeding
Any vaginal bleeding after menopause (defined as 12 months without a period) is abnormal and requires medical evaluation, regardless of how light it is:
- Spotting or light staining
- Pink, brown, or watery discharge
- A single episode of fresh bleeding
It is important to know that only about 1 in 10 women with postmenopausal bleeding actually have cancer — most have benign causes such as polyps, thinning tissues, or hormone effects. However, only a medical examination can distinguish between them.
Symptoms in Women Who Have Not Yet Reached Menopause
- Periods that are heavier or longer than usual (menorrhagia)
- Bleeding between periods (metrorrhagia)
- Periods that become irregular or occur more frequently
- Spotting after intercourse
- Watery, pink, or blood-stained discharge
Other Possible Symptoms
- Pelvic pain, cramping, or a feeling of pressure in the lower abdomen — more common when the tumor is large or has spread
- Pain during sexual intercourse (dyspareunia)
- Pain or difficulty when urinating, or pain during bowel movements (if the tumor presses on or invades adjacent organs)
- Unexplained difficulty emptying the bladder or bowels
Symptoms of Advanced or Metastatic Disease
- Unintentional weight loss, loss of appetite, persistent fatigue
- Abdominal swelling or distension (due to fluid accumulation or tumor spread)
- Persistent lower back pain or bone pain
- Shortness of breath or chronic cough (if the cancer has spread to the lungs)
- Enlarged lymph nodes in the groin
When to seek medical attention urgently: See a doctor without delay if you experience any bleeding after menopause**, bleeding between periods that persists or recurs, unusually heavy periods that do not respond to usual management, or persistent watery/bloody discharge. Early evaluation dramatically improves outcomes.
How Is It Diagnosed?
The diagnostic pathway for suspected endometrial cancer usually involves several steps:
- Medical history and physical examination — including a pelvic examination and review of risk factors and family history.
- Transvaginal ultrasound (TVUS) — a first-line, painless test. If the endometrial lining measures more than about 4–5 mm in a postmenopausal woman with bleeding, tissue sampling is recommended.
- Endometrial biopsy (pipelle sampling) — a thin, flexible tube is inserted through the cervix in an outpatient setting to suction a small tissue sample. This detects the vast majority of cancers.
- Hysteroscopy with targeted biopsy — a thin camera is passed into the uterine cavity, allowing the doctor to see the lining directly and take samples from suspicious areas. This is the most accurate way to identify focal lesions and polyps.
- Dilation and curettage (D&C) — performed under anesthesia when outpatient sampling is impossible or results are inconclusive.
- Staging imaging — after cancer is confirmed:
- MRI of the pelvis — best for assessing how deeply the tumor invades the muscle wall and whether the cervix is involved
- CT of the chest, abdomen, and pelvis — to look for spread to lymph nodes or distant organs
- Chest X-ray — a basic check of the lungs
- Blood tests — general health assessment; the marker CA-125 may be elevated in advanced disease.
- Molecular/genetic testing of the tumor — now standard practice. This includes testing for mismatch-repair deficiency (dMMR/MSI), which can suggest Lynch syndrome (important for the patient’s family and for immunotherapy decisions), as well as p53 and POLE status, which affect prognosis and treatment planning.
Staging and Grading
Staging describes how far the cancer has spread and guides treatment. The current system is provided by FIGO (International Federation of Gynecology and Obstetrics), updated in 2023 to include molecular features.
Table 4. Simplified FIGO staging of endometrial cancer
| Stage | Description |
|---|---|
| Stage I | Cancer is confined to the body of the uterus (may invade the muscle wall but has not spread elsewhere) |
| Stage II | Cancer has spread to the cervix, or shows substantial spread into blood/lymph vessels, but remains within the pelvic region of the uterus |
| Stage III | Cancer has spread locally to the ovaries, fallopian tubes, vagina, tissues around the uterus, or pelvic/para-aortic lymph nodes |
| Stage IV | Cancer has invaded the bladder or bowel, or spread to distant organs (liver, lungs, bones, distant lymph nodes) |
Treatment
Treatment is individualized and depends on the stage and grade of the tumor, its molecular characteristics, and the patient’s age, general health, and personal wishes.
1. Surgery — The Cornerstone of Treatment
For most women, the standard operation includes:
- Total hysterectomy — removal of the uterus (and usually the cervix)
- Bilateral salpingo-oophorectomy — removal of both fallopian tubes and ovaries
- Sentinel lymph node biopsy or lymph node assessment — removal and examination of key lymph nodes to check for spread
Surgery is usually performed minimally invasively (laparoscopically or robotically), which allows faster recovery. Surgery alone cures the majority of early-stage, low-grade cancers.
2. Radiation Therapy
- Vaginal brachytherapy — internal radiation applied to the vagina after surgery; commonly used to reduce recurrence risk in intermediate-risk patients
- External beam radiation therapy (EBRT) — external radiation to the pelvis, used for patients at higher risk of local recurrence
- Can also be used as the main treatment for women unable to undergo surgery
3. Chemotherapy
- Usually a combination of carboplatin + paclitaxel
- Used for advanced, recurrent, or high-risk/aggressive subtypes (e.g., serous carcinoma)
- May be given alongside or after radiation
4. Hormone (Endocrine) Therapy
- Progestins (e.g., medroxyprogesterone, megestrol) or progestin-releasing intrauterine devices
- Effective for slow-growing, hormone-receptor-positive tumors
- Used in advanced low-grade disease and for fertility preservation
5. Immunotherapy and Targeted Therapy (Newer Options)
- Pembrolizumab and dostarlimab — immune checkpoint inhibitors, particularly effective for tumors with mismatch-repair deficiency (dMMR/MSI-high)
- Lenvatinib + pembrolizumab — a targeted/immune combination approved for advanced disease after prior chemotherapy
- Trastuzumab added to chemotherapy for HER2-positive serous carcinoma
6. Fertility-Sparing Treatment (Selected Cases Only)
Young women with early-stage (Stage IA, grade 1) endometrioid cancer without muscle invasion who wish to preserve fertility may be offered:
- High-dose progestin therapy (oral and/or via intrauterine device)
- Hysteroscopic removal of the tumor
- Very close monitoring with repeated biopsies
After completing childbearing, hysterectomy is generally recommended because of the risk of recurrence.
Table 5. Typical treatment approach by stage (simplified)
| Situation | Usual approach |
|---|---|
| Stage I, low-risk | Surgery alone; possible vaginal brachytherapy |
| Stage I–II, intermediate/high-risk | Surgery + radiotherapy and/or chemotherapy |
| Stage III | Surgery (if feasible) + chemotherapy and radiotherapy |
| Stage IV / recurrent | Chemotherapy ± immunotherapy/targeted therapy; hormonal therapy for selected low-grade tumors; surgery if suitable |
| Unable to have surgery | Radiation therapy ± systemic treatment |
Prognosis and Survival
Endometrial cancer has a favorable prognosis overall, largely because of early detection. Survival depends mainly on the stage at diagnosis, tumor grade and type, the woman’s age, and molecular features.
Table 6. Approximate 5-year relative survival rates by extent of disease*
| Extent of disease | Approx. 5-year survival |
|---|---|
| Confined to the uterus (localized) | ~95% |
| Spread to nearby tissues/lymph nodes (regional) | ~70% |
| Spread to distant organs (distant/metastatic) | ~20% |
| All stages combined | ~80–85% |
Figures are population averages based on recent registry data; individual outcomes may differ, and treatments are continually improving.*
Favorable prognostic factors: early stage, low grade, endometrioid type, younger age, POLE-mutated molecular profile.
Unfavorable prognostic factors: high grade, serous/clear cell/carcinosarcoma histology, deep muscle invasion, lymph node involvement, p53-abnormal profile.
Can Endometrial Cancer Be Prevented?
There is no guaranteed way to prevent the disease, and no routine population screening test exists (the Pap smear detects cervical, not endometrial, cancer). However, risk can be meaningfully reduced:
- ✅ Maintain a healthy body weight — obesity is the strongest modifiable risk factor
- ✅ Exercise regularly — even moderate activity lowers risk
- ✅ Manage diabetes and blood pressure effectively
- ✅ Discuss hormonal therapy carefully — estrogen for menopausal symptoms should be combined with progestin in women who still have a uterus
- ✅ Consider genetic counseling and testing if close relatives have had endometrial or bowel cancer (possible Lynch syndrome); carriers may be offered risk-reducing surgery or enhanced surveillance
- ✅ Do not ignore abnormal bleeding — prompt evaluation of postmenopausal or irregular bleeding enables early diagnosis, which is the single most important factor for successful treatment
Living With and After Endometrial Cancer
A cancer diagnosis affects every area of life. Important aspects of care after treatment include:
- Regular follow-up visits — typically every 3–6 months for the first 2–3 years, then less frequently, to detect any recurrence early
- Managing menopausal symptoms — removal of the ovaries causes immediate surgical menopause; survivorship care teams can help with hot flushes, bone and heart health
- Pelvic floor and sexual health — recovery after surgery or radiation may require specialist physiotherapy and open discussion with your care team
- Emotional support — psychological counseling, patient support groups, and peer communities make a demonstrated difference to quality of life
- Healthy lifestyle — balanced nutrition, physical activity, and weight management support recovery and overall wellbeing
Many women treated for early-stage endometrial cancer go on to live long, full lives. Being informed, attending follow-up appointments, and communicating openly with your healthcare team are the best tools for long-term wellbeing.
Key Takeaways
📌 Endometrial cancer is the most common gynecological cancer in developed countries and usually affects women after menopause.
📌 Its hallmark symptom — abnormal vaginal bleeding, especially after menopause — appears early, making most cases highly curable when evaluated promptly.
📌 Obesity, unopposed estrogen exposure, and hereditary syndromes such as Lynch syndrome are major risk factors.
📌 Diagnosis relies on transvaginal ultrasound and endometrial biopsy; treatment usually starts with surgery, supported by radiation, chemotherapy, hormonal therapy, immunotherapy, or targeted drugs as needed.
📌 A healthy lifestyle and rapid medical assessment of unusual bleeding are the most powerful tools women have against this disease.
Disclaimer: This article provides general information and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider with any questions regarding a medical condition.
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