Endometrial cancer

What is endometrial cancer?

Cancer of the endometrium, or uterine cancer, is mainly adenocarcinoma arising from the lining of the uterus and is an oestrogen-dependent tumour. This is distinct from carcinoma of the cervix which is squamous cell carcinoma. Cancer of the body of the uterus could include myometrial sarcoma.

Types of endometrial cancer

The vast majority of cancers of the endometrium (80%) are adenocarcinomas. They may be undifferentiated.

There are two main types of endometrial cancer, corresponding to oestrogen-dependent endometrioid (type 1) and oestrogen-independent non-endometrioid carcinomas (type 2).¹

Who gets endometrial cancer? (Epidemiology)

Women aged 75 - 79 make up the group with the highest incidence of endometrial cancer in the UK. Endometrial cancer is the fourth most common cancer in women in the UK, with around 10,185 new cases per year, around one-third of which are preventable.²

Endometrial cancer risk factors

Prolonged periods of unopposed oestrogen are the main risk factor. When oestrogen is not modified by the effects of progesterone, this is termed 'unopposed oestrogen'.

This may occur as a result of medication or in anovulatory cycles where the corpus luteum does not mature and secrete progesterone. The histological diagnosis can be difficult in that gross endometrial hyperplasia can look like a well-differentiated carcinoma.

Risk factors for endometrial cancer include:³

• Being nulliparous.

• Medical conditions such as polyendocrine metabolic ovarian syndrome (previously known as polycystic ovarian syndrome) which predispose to anovulatory cycles.

• Younger menarche or older menopause.

• Obesity and diabetes - adipose tissue contains oestrogen and it is estimated that 34% of cases of endometrial cancer in the UK are caused by obesity or being overweight. There is a link to diabetes but this may largely be explained by the links between diabetes and obesity.

• Atypical endometrial hyperplasia, which may progress to endometrial cancer and shares its risk factors. 8.2%).

• Genetic conditions such as Lynch syndrome.

• The use of tamoxifen for the treatment of breast cancer.

• Unopposed oestrogen given as hormone replacement therapy (HRT) - women with a uterus should always be given a progestogen when they take HRT.

• Protective factors include use of combined hormonal contraception, and a possible link to physical activity and drinking coffee.

Endometrial cancer symptoms

History⁴

The classic symptom of endometrial cancer is postmenopausal bleeding (PMB); the National Institute for Health and Care Excellence (NICE) guidance on suspected cancer says that women with unexplained post-menopausal bleeding that cannot be attributed to HRT be referred on a suspected cancer pathway. In their section on endometrial cancer, NICE also advise an urgent direct access ultrasound for women who are 55 or over and have the following:

• Unexplained vaginal discharge:

  • For the first time or

  • With thrombocytosis or

  • With haematuria.

• Visible haematuria:

  • With a low haemoglobin or

  • With thrombocytosis or

  • With high blood glucose levels.

Women who take continuous combined HRT have a risk of endometrial cancer which is significantly lower than that of the general population, and bleeding in this cohort should not be referred on the suspected cancer pathway. Instead, the woman's risk of endometrial cancer should be assessed using the flowchart in the British Menopause Society's guidance on unscheduled bleeding on HRT⁵ and the appropriate action taken. Depending on the risk factors, this may include a transvaginal ultrasound scan, an urgent suspected cancer pathway referral, or optimising the woman's HRT.

Anyone referred on the urgent suspected cancer pathway should have cancer diagnosed or ruled out within 28 days - this target has replaced the previous one of being seen within two weeks.

Examination

Unless the disease is well advanced there is unlikely to be any physical abnormality, but examination is always useful - an abnormality of the cervix or genitourinary syndrome of the menopause may be found to be the sole cause, or a contributor to, any unusual bleeding.

If the woman has not had a cervical smear in the appropriate period since her last one, and is aged 64 or under, this should be done when she is seen. This is however a screening test and further investigation or referral should not be delayed pending the smear result.

Investigating endometrial cancer

Transvaginal ultrasound (TVUS) scan

TVUS scan is the usual first-line procedure to identify which women with PMB are at higher risk of endometrial cancer. In most cases, an urgent suspected cancer pathway referral done for PMB will lead to a 'one-stop shop' clinic where a scan is done and the woman is seen with the result.

The mean endometrial thickness in postmenopausal women is much thinner than in premenopausal women. Thickening of the endometrium may indicate the presence of pathology. In general, the thicker the endometrium, the higher the likelihood of important pathology - ie endometrial cancer being present.

TVUS using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy. Some centres use 4 mm or even 5 mm as a cut-off for endometrial biopsy.

In addition, malignant and benign endometrial patterns can often be determined by TVUS which can help diagnosis.

Endometrial biopsy

A definitive diagnosis in PMB is made by histology. A sample is usually obtained by endometrial biopsy taken during an outpatient hysteroscopy. All methods of sampling the endometrium will miss some cancers.

Endometrial cancer staging

Total abdominal hysterectomy with bilateral salpingo-oophorectomy is required both as a primary treatment and for the purpose of staging.

In brief, the staging of endometrial cancer is as follows. More details can be found in the relevant guidance from 2023:⁶

• Stage 1 - confined to the body of the uterus.

• Stage 2 - extension to the cervical stroma.

• Stage 3 - local or regional spread outside the uterus.

• Stage 4 - local spread to the bladder or rectal mucosa. metastasis to the extrapelvic peritoneum or more distantly.

Endometrial cancer treatment and management

Treatment options depend upon the endometrial cancer stage and may include surgery, radiotherapy or chemotherapy.

Recurrence

• Recurrence may respond to radiotherapy. Radical radiotherapy for local recurrence is effective in over half the cases.

• The standard treatment of vaginal recurrence is radiation therapy.

• Systemic treatment of metastatic and relapsed disease may involve endocrine therapy or cytotoxic chemotherapy.

Endometrial cancer prognosis²

Overall ten-year survival in the UK is 71.7%; this varies with age, increasing to 80.1% for those aged under 45 and dropping to 54.8% for those aged 75 or over.

Those women who are diagnosed early have a far better prognosis. One-year survival is 92.4% for those diagnosed at stage 1 but only 46.9% for those diagnosed at stage 4.