Endometrial Cancer
Endometrial cancer arises from the endometrium, the lining of the uterus, and is the most common type of uterine cancer. It most often presents with post-menopausal bleeding.
Updated UKMLA guide to endometrial cancer based on the BGCS guideline: risk factors, symptoms, diagnosis, referral, and management.
Definition
Endometrial cancer is a specific type and the most common form of uterine cancer.
Endometrial cancer arises from the endometrium, the lining of the uterus (womb).
Histology
Most common histological type: adenocarcinoma
- To be precise, the most common type is endometrioid carcinoma, which is a type of adenocarcinoma
Other less common types include:
- Serous carcinoma
- Clear cell carcinoma
Epidemiology
Uterine cancer is the 4th most common cancer in females in the UK
Peak incidence: 75-79 y/o
Causes and Risk Factors
| Type | Description | Risk factors |
|---|---|---|
| Type I (~80%) [Ref] | Strongly linked to oestrogen excess (oestrogen stimulates growth of endometrium without being opposed by progesterone)
Better prognosis: lower-grade and slower-growing |
|
| Type II | Unrelated to oestrogen exposure
Worse prognosis: higher-grade and aggressive |
|
Lynch syndrome (HNPCCHereditary nonpolyposis colorectal cancer) is a major inherited genetic cause of endometrial cancer
- Lynch syndrome is considered a major risk factor for endometrial cancer (both type I and II)
- 40-60% lifetime risk of developing endometrial cancer
- ~3% of all endometrial cancers are directly caused by Lynch syndrome
- Autosomal dominant mutation in DNA mismatch repair genes (e.g. MLH1, MSH2)
- Other manifestations
- Early-onset colorectal cancer (see the Colorectal Cancer article for more information)
- Gastric cancer
- Ovarian cancer
Note that the following are protective factors against developing endometrial cancer
- COCP (the progesterone counters oestrogen exposure)
- LNG-IUS (the progesterone counters oestrogen exposure)
- Smoking
- Note that the BGCS guideline did NOT comment on smoking as a protective factor
- However, traditional teaching considers smoking as a protective factor, supported by the general medical literature [Ref]
Clinical Features
Post-menopausal women (more common):
- Post-menopausal bleeding – most common symptom
- Defined as vaginal bleeding that occurs at least 1 year after the last menstrual period in those who are NOT taking HRTHormone replacement therapy
- ~50% probability of endometrial cancer in >70 y/o women presenting with post-menopausal bleeding (overall probability is 50-10%)
- Unscheduled bleeding (unexpected / persistent bleeding) on HRTHormone replacement therapy
- Abnormal vaginal discharge
- Haematuria
Pre-menopausal women:
- Persistent intermenstrual bleeding
- Heavy menstrual bleeding
Features of advanced disease:
- Abdominal pain, distension, bloating
- Changes in bowel or bladder habits
- New cough (suggest lung metastasis)
Frequent sites for spread and metastasis:
- Adjacent pelvic structures (e.g. vagina, ovaries, fallopian tubes, parametrium, bladder, rectum)
- Pelvic and para-aortic lymph nodes
- Lungs – primary site for distant spread
- Other: liver, bones, peritoneum and abdominal cavity
Red Flags and When to Refer
Since clinical features alone do not distinguish endometrial hyperplasia from endometrial cancer, the same red flags and referral indications apply for both endometrial hyperplasia and cancer.
The only way to definitively distinguish between endometrial hyperplasia and cancer is via biopsy and histological examination.
For ≥55 y/o individuals with female reproductive organs (including women, trans-men and non-binary people):
| Action | Indications |
|---|---|
| Suspected cancer pathway referral (to receive a diagnosis or exclusion of cancer within 28 days) | >55 y/o with unexplained post-menopausal bleeding that cannot be attributed to HRTHormone replacement therapy* |
| Consider an urgent (within 2 weeks) TVUSTrans-vaginal ultrasound | Unexplained vaginal discharge PLUS any of the following
|
Visible haematuria PLUS any of the following
|
*if <55 y/o with unexplained post-menopausal bleeding → consider a suspected cancer pathway referral
Red flags and referral for women who are taking HRTHormone replacement therapy:
- Bleeding >6 months after initiating HRT
- Bleeding >3 months after changing HRT (dose / regimen)
See the Hormone Replacement Therapy (HRT) article for details on the management of unscheduled bleeding on HRT.
Investigation and Diagnosis
Pre-Diagnosis Investigations
1st line: TVUSTrans-vaginal ultrasound
- Purpose: measure the double-layer endometrial thickness
- An endometrial thickness of ≥4 mm requires further investigation
- The 4mm cut-off is specifically for post-menopausal women who are NOT on HRTHormone replacement therapy
- Any abnormal bleeding in tamoxifen users should prompt urgent investigation, as ultrasound is unreliable in these patients
While TVUSTrans-vaginal ultrasound is a useful imaging tool, its primary role is to measure the thickness and structure of the endometrial lining to determine if further testing is needed. It is useful in ruling out disease; if the endometrial thickness is below the cut-off, the probability of cancer is reduced to <1%
TVUSTrans-vaginal ultrasound alone cannot reliably distinguish between endometrial hyperplasia and endometrial cancer. Histological examination (biopsy) is the only reliable way.
Further investigation (definitive): outpatient endometrial biopsy (e.g. Pipelle biopsy)
- If the patient has persistent / recurrent bleeding despite a -ve biopsy → hysteroscopy for direct visualisation
Tumour marker CA125 is NOT recommended for routine testing.
CA125 may be raised non-specifically in the presence of bulky metastatic disease. Its main clinical role is in the diagnostic work-up of ovarian cancer.
Post-Diagnosis Work-Up
| Purpose | Investigations |
|---|---|
| Staging |
|
| Lynch syndrome screening | Immunohistochemistry testing for mismatch repair deficiency – ALL patients |
| Lymph node assessment | Sentinel lymph node biopsy |
Management
| Clinical category | Corresponding FIGO stage | Management principles |
|---|---|---|
| Locally early | I (confined to the uterus) | Total hysterectomy with bilateral salpingo-oophorectomy
A minimally invasive (laparoscopic or robotic) approach is recommended |
| Locally overt | II (invaded the cervical stroma, but not beyond the uterus) | Total hysterectomy with bilateral salpingo-oophorectomy
Either minimally invasive or open surgery is appropriate (depending on the patient’s frailty, size of uterus, extent of tumour) |
| Locally advanced | III (spread to serosa, adnexae, vagina, parametrium, or pelvic/para-aortic lymph nodes) / IVA (invasion to bladder or bowel mucosa) | 2 approaches:
|
| Metastatic | IVB (distant metastasis e.g. to the lungs, liver, bones, inguinal lymph nodes) | Systemic therapy
|
- Eligibility: ONLY stage 1 AI endometrial cancer (no myometrial invasion) or atypical endometrial hyperplasia
- Treatment options:
- Mainstay: primary hormonal therapy for 6-12 months (oral progestins or LNG-IUSLevonorgestrel-releasing intrauterine system)
- Alternative: combination of progestins with GnRH or metformin
- A hysteroscopic resection to remove visible tumour bulk prior to starting progestin therapy may be considered
References
Related Articles
Heavy Menstrual Bleeding (HMB)
Hormone Replacement Therapy (HRT)