Endometrial Cancer
Summary
Endometrial cancer is the most common gynaecological malignancy in developed countries, arising from the lining of the uterus. The majority (80%) are Type 1 (endometrioid adenocarcinoma), which are oestrogen-dependent and have a good prognosis. Type 2 cancers (serous, clear cell) are oestrogen-independent with poorer outcomes. The cardinal symptom is postmenopausal bleeding (PMB), which warrants urgent investigation. Risk factors relate to unopposed oestrogen exposure: obesity, PCOS, tamoxifen, nulliparity, and late menopause. Diagnosis is by transvaginal ultrasound (endometrial thickness >4mm suspicious) followed by endometrial biopsy. Treatment is primarily surgical (hysterectomy + BSO), with adjuvant therapy for high-risk cases.
Key Facts
- Most Common: Gynaecological cancer in developed countries
- Types: Type 1 (endometrioid, 80%, good prognosis); Type 2 (serous/clear cell, poorer)
- Key Symptom: Postmenopausal bleeding (PMB) - presents early
- Risk Factors: Obesity, PCOS, Tamoxifen, Nulliparity, Late menopause, Lynch syndrome
- Investigation: TVUS (thickness >4mm) → Pipelle/Hysteroscopy biopsy
- Treatment: Total hysterectomy + BSO
Clinical Pearls
"PMB = Endometrial Cancer Until Proven Otherwise": 10% of women with postmenopausal bleeding have endometrial cancer. Always investigate.
"Oestrogen Unopposed = Risk": Any cause of prolonged oestrogen without progesterone opposition increases risk - obesity (aromatase), PCOS, HRT (oestrogen-only), tamoxifen.
"4mm Rule": Endometrial thickness >4mm on TVUS in a woman with PMB requires biopsy. <4mm has high negative predictive value.
"Early Stage = Good Prognosis": 75% present at Stage I due to early bleeding, with 5-year survival >90%.
Incidence
- Most common gynaecological cancer in UK/USA
- ~9,700 cases/year in UK
- Incidence rising (linked to obesity epidemic)
Demographics
- Peak age: 60-70 years
- 75% are postmenopausal
- Increasing in younger women (obesity, PCOS)
Risk Factors
| Factor | Mechanism |
|---|---|
| Obesity | Adipose tissue converts androgens to oestrogen (aromatase) |
| PCOS | Anovulation → Unopposed oestrogen |
| Nulliparity | More lifetime menstrual cycles |
| Late menopause | Prolonged oestrogen exposure |
| Early menarche | Prolonged oestrogen exposure |
| Tamoxifen | Oestrogenic effect on endometrium |
| Oestrogen-only HRT | Unopposed oestrogen |
| Lynch syndrome (HNPCC) | 40-60% lifetime risk |
| Diabetes / Hypertension | Associated with metabolic syndrome |
Protective Factors
- Combined oral contraceptive pill (progesterone)
- Multiparity
- Breastfeeding
- Smoking (anti-oestrogenic - but not recommended!)
Types of Endometrial Cancer
| Type | Frequency | Features | Prognosis |
|---|---|---|---|
| Type 1 (Endometrioid) | 80% | Oestrogen-dependent; arises from hyperplasia; low grade | Good |
| Type 2 (Serous/Clear Cell) | 20% | Oestrogen-independent; arises from atrophic endometrium; high grade | Poor |
Molecular Subtypes (TCGA)
- POLE ultramutated (best prognosis)
- Microsatellite unstable (Lynch-like)
- Copy number low
- Copy number high (p53 mutant, worst prognosis)
Progression
- Normal endometrium
- Endometrial hyperplasia (without atypia)
- Atypical hyperplasia (precursor)
- Endometrial carcinoma
Symptoms
| Feature | Notes |
|---|---|
| Postmenopausal bleeding | 90% of cases; Any PMB needs investigation |
| Abnormal premenopausal bleeding | Heavy, irregular, intermenstrual |
| Vaginal discharge | May be blood-stained or purulent |
| Pelvic pain | Late symptom (advanced disease) |
| Abdominal distension | Advanced disease |
Why Early Presentation?
General
- Often normal in early disease
- Obesity common
Abdominal
- May be unremarkable
- Palpable mass (advanced)
- Ascites (advanced)
Pelvic/Speculum
- Bleeding from os
- Enlarged uterus (may be bulky)
First-Line
| Test | Notes |
|---|---|
| Transvaginal Ultrasound (TVUS) | Measure endometrial thickness; >mm in PMB = suspicious |
| Pipelle endometrial biopsy | Outpatient; first-line for tissue diagnosis |
Second-Line
| Test | Notes |
|---|---|
| Hysteroscopy + Biopsy | If Pipelle non-diagnostic or TVUS abnormal |
| MRI pelvis | Staging: Depth of myometrial invasion, nodal involvement |
| CT CAP | Staging: Distant metastases |
Histology
- Confirms adenocarcinoma
- Grade 1-3 (differentiation)
- Type (endometrioid vs serous/clear cell)
Staging (FIGO 2009)
| Stage | Description |
|---|---|
| I | Confined to uterus |
| II | Cervical stromal invasion |
| III | Local/regional spread (adnexa, vagina, nodes) |
| IV | Bladder/bowel mucosa or distant metastases |
Treatment Approach
┌──────────────────────────────────────────────────────────┐
│ ENDOMETRIAL CANCER MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ SURGERY (Mainstay for most): │
│ • Total Laparoscopic Hysterectomy (TLH) │
│ • Bilateral Salpingo-Oophorectomy (BSO) │
│ • +/- Pelvic/Para-aortic Lymphadenectomy │
│ • Peritoneal washings │
│ │
│ ADJUVANT THERAPY (Based on risk): │
│ • Low risk (Stage IA, G1-2): Observation │
│ • Intermediate risk: Vaginal brachytherapy │
│ • High risk: External beam radiotherapy +/- chemo │
│ • Type 2 (serous/clear cell): Chemotherapy │
│ │
│ INOPERABLE/ADVANCED: │
│ • Palliative radiotherapy │
│ • Chemotherapy (carboplatin/paclitaxel) │
│ • Hormonal therapy (progestins if ER+) │
│ │
│ FERTILITY-SPARING (Rare; highly selected): │
│ • Young women, Stage IA Grade 1 │
│ • High-dose progestins + close surveillance │
│ │
└──────────────────────────────────────────────────────────┘
Follow-Up
- Clinical examination every 3-6 months for 2 years
- Symptom-based imaging
- No role for routine imaging in asymptomatic patients
Of Disease
- Local invasion (bladder, bowel)
- Lymph node metastases
- Distant metastases (lung, liver)
Of Treatment
- Surgical: Bleeding, infection, lymphoedema, VTE
- Radiotherapy: Bowel/bladder toxicity, vaginal stenosis
- Chemotherapy: Myelosuppression, neuropathy
Survival by Stage
| Stage | 5-Year Survival |
|---|---|
| I | 90%+ |
| II | 75-80% |
| III | 40-60% |
| IV | 15-25% |
Prognostic Factors
| Good | Poor |
|---|---|
| Early stage | Advanced stage |
| Low grade | High grade |
| Endometrioid type | Serous/Clear cell |
| Superficial invasion | Deep myometrial invasion |
| ER/PR positive | p53 mutation |
Key Guidelines
- NICE NG88: Suspected Cancer Recognition and Referral
- BGCS: Uterine Cancer Guidelines
- ESMO Clinical Practice Guidelines
Key Evidence
Investigation
- TVUS + Pipelle as first-line is cost-effective
Treatment
- Laparoscopic surgery has equivalent oncological outcomes to open
What is Endometrial Cancer?
Endometrial cancer is cancer of the lining of the womb (uterus). It's the most common gynaecological cancer in the UK.
What Are the Symptoms?
The main symptom is vaginal bleeding after menopause. If you have any bleeding after your periods have stopped, see your GP straight away. In younger women, very heavy or irregular periods can also be a sign.
Who is at Risk?
- Being overweight
- Not having had children
- Taking tamoxifen
- Having a family history of certain cancers (Lynch syndrome)
How is it Diagnosed?
- An ultrasound scan to look at the womb lining
- A small sample (biopsy) to check for cancer cells
How is it Treated?
Most women have surgery to remove the womb and ovaries. Some may need radiotherapy or chemotherapy afterwards.
What Are the Chances of Recovery?
Because the cancer usually causes bleeding early on, most women are diagnosed at an early stage. The outlook is very good for early-stage disease - more than 9 out of 10 women are cured.
Primary Guidelines
- NICE Guideline [NG12]. Suspected Cancer: Recognition and Referral. 2015, updated 2023.
- British Gynaecological Cancer Society. Uterine Cancer Guidelines.
Key Studies
- Crosbie EJ, et al. Endometrial cancer. Lancet. 2022;399(10333):1412-1428. PMID: 35397864