Endometrial Cancer

Question 1

… is the most common gynaecological malignancy in developed countries.

Answer 1

Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries.

Question 2

The five-year survival of endometrial cancer is more favourable than some cancers, estimated around 75%. Why?

Answer 2

Early presentation with bleeding is common

Question 3

What is endometrial cancer strongly linked to?

Answer 3

EC is strongly linked to obesity. The rising rates of obesity has led to a significant increase in the incidence of EC. It is the sixth most common female malignancy worldwide.

Question 4

2-5% of cases, EC is linked to a familial cancer syndrome called … syndrome. This is due to an inherited mutation in one of the mismatch repair genes. It can lead to early onset endometrial and colorectal cancer.

Answer 4

2-5% of cases, EC is linked to a familial cancer syndrome called Lynch syndrome. This is due to an inherited mutation in one of the mismatch repair genes. It can lead to early onset endometrial and colorectal cancer.

Question 5

EC is broadly divided into two main types….

Answer 5

EC is broadly divided into two main types: endometrioid and non-endometrioid.

Question 6

Endometrioid (Type I) endometrial cancer

Answer 6

75-80% of EC. Earlier presentation and better prognosis. Stimulated by oestrogen. Typically follows period of endometrial hyperplasia.

Question 7

Non-endometrioid (Type II) endometrial cancer

Answer 7

10-20% of EC. Multiple subtypes of tumour (e.g. serous, clear cell, mucinous). Serous and clear cell not associated with obesity and not stimulated by oestrogen.

Question 8

EC is most commonly seen in post-menopausal women due to prolonged exposure to …

Answer 8

EC is most commonly seen in post-menopausal women due to prolonged exposure to oestrogen.

Question 9

Why are obesity and endometrial cancer linked?

Answer 9

Obesity is associated with an excess of adipose tissue. Adipose tissue, or fat, is not inert and secretes a number of peptide and steroid hormones. Adipose tissue increases the level of oestrogen because of the enzyme aromatase that is able to convert androgens to oestrogen. This increase in oestrogen is a major factor in the pathogenies of EC.

Question 10

Risk factors for endometrial cancer

Answer 10

Unopposed oestrogen therapy
Increasing age
Tamoxifen therapy
Early menarche & late menopause: increased time expose to oestrogen
Nulliparity: never borne a child
Polycystic ovarian syndrome: chronic anovulation
Genetic risk (e.g. Lynch syndrome)

Question 11

What is lynch syndrome?

Answer 11

LS is an inherited cancer syndrome, which is due to a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). When genetic mutations occur in germ cells, these can be passed onto our offspring and will be present in every cell within the body. The hallmark of LS is abnormal DNA repair, which leads to DNA replication errors that we call microsatellite instability (MSI). It can lead to early onset EC and colorectal cancer.

Question 12

What is the classical presentation of endometrial cancer?

Answer 12

Post-menopausal bleeding

Question 13

Define post menopausal bleeding

Answer 13

PMB is defined as abnormal vaginal bleeding ≥12 months after the last menstrual period in patients not on hormone replacement therapy (HRT). EC is detected in 5-10% of patients with PMB. It can be more difficult to diagnosis patients peri-/premenopausal.

Question 14

Symptoms of endometrial cance

Answer 14

Postmenopausal bleeding
Abnormal uterine bleeding: intermenstrual, frequent, heavy or prolonged
Constitutional symptoms: weight loss, anorexia, lethargy

Question 15

Signs of endometrial cancer

Answer 15

Physical examination: typically normal (fixed, hard uterus suggests advanced disease)
Cervical evaluation: may see abnormal tissue on speculum examination

Question 16

Two week wait urgent referral for PMB - what ages should it be considered/definitive?

Answer 16

Referral: age > 55 years and PMB
Consider referral: age < 55 years and PMB

Question 17

Diagnosis + investigation of endometrial cancer

Answer 17

Patients with suspected EC require an abdominal, pelvic and speculum examination alongside a transvaginal ultrasound.

Question 18

Currently, a transvaginal ultrasound (TVUS) is the initial investigation of choice to assess the endometrial thickness in patients presenting with PMB. In the absence of any endometrial irregularity, a thickness level at …mm is the cut-off for further investigation.

Answer 18

Currently, a transvaginal ultrasound (TVUS) is the initial investigation of choice to assess the endometrial thickness in patients presenting with PMB. In the absence of any endometrial irregularity, a thickness level at 4mm is the cut-off for further investigation.

Question 19

What is the investigation of choice to assess endometrial thickness?

Answer 19

Currently, a transvaginal ultrasound (TVUS) is the initial investigation of choice to assess the endometrial thickness in patients presenting with PMB. In the absence of any endometrial irregularity, a thickness level at 4mm is the cut-off for further investigation.

Question 20

< …mm endometrial thickness: no further investigation required unless recurrent PMB
≥ …mm endometrial thickness: offer endometrial sampling, ideally as outpatient

Answer 20

< 4mm endometrial thickness: no further investigation required unless recurrent PMB
≥ 4 mm endometrial thickness: offer endometrial sampling, ideally as outpatient

Question 21

Endometrial sampling

Answer 21

Pipelle biopsy: completed in outpatient setting. Small straw-like tube (pipelle) is passed through the cervix to take an endometrial sample.
Hysteroscopy and biopsy: hysteroscope passed into uterus for direct visualisation. Reserved for high-risk patients or those with focal area of irregularity. Required in patients unable to tolerate outpatient pipelle biopsy (e.g. cervical stenosis, discomfort). Regional or general anaesthesia.

Question 22

What is used to grade and stage the tumour in endometrial cancer?

Answer 22

International Federation of Obstetrics and Gynecology (FIGO)

Question 23

A cell that does not resemble the original cell type is said to be ‘… differentiated’ and associated with more aggressive behaviour and worse outcome. A cell that does resemble the original cell type is said to be ‘… differentiated’ and generally associated with a better outcome.

Answer 23

A cell that does not resemble the original cell type is said to be ‘poorly differentiated’ and associated with more aggressive behaviour and worse outcome. A cell that does resemble the original cell type is said to be ‘well differentiated’ and generally associated with a better outcome.

Question 24

Surgical treatment options for endometrial cancer

Answer 24

Surgical treatment: total hysterectomy (removal of uterus) +/- bilateral salpingoopherectomy (removal or ovaries and fallopian tubes). Generally first-line option in early stage disease. Different surgical methods. May be combined with lymph node dissection.

Question 25

If unfit for surgery, how to manage endometrial cancer?

Answer 25

options can include vaginal hysterectomy (regional anaesthesia), pelvic radiotherapy or hormonal therapy with progestogens or aromatase inhibitors.

Question 26

Fertility-sparing treatment for endometrial cancer

Answer 26

<5% of EC occur in women under 45 years. Requires specialist gynae-oncology input with consideration of risk/benefits. Progestogens in selected patients, requires individualised care and regular follow-up.