Endometrial Cancer

Endometrial cancer is cancer of the endometrium, the lining of the uterus. Around 80% of cases are adenocarcinoma. It is an oestrogen-dependent cancer, meaning that oestrogen stimulates the growth of endometrial cancer cells.

TOM TIP: For your exams, any woman presenting with postmenopausal bleeding has endometrial cancer until proven otherwise. The key risk factors to remember are obesity and diabetes.

 

Endometrial Hyperplasia

Endometrial hyperplasia is a precancerous condition involving thickening of the endometrium. The risk factors, presentation and investigations of endometrial hyperplasia are similar to endometrial cancer. Most cases of endometrial hyperplasia will return to normal over time. Less than 5% go on to become endometrial cancer. There are two types of endometrial hyperplasia to be aware of:

  • Hyperplasia without atypia 
  • Atypical hyperplasia

 

Endometrial hyperplasia may be treated by a specialist using progestogens, with either:

  • Intrauterine system (e.g. Mirena coil)
  • Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)

 

Risk Factors

You can think of the risk factors for endometrial cancer in relation to the patient’s exposure to unopposed oestrogen. Unopposed oestrogen refers to oestrogen without progesterone. Unopposed oestrogen stimulates the endometrial cells and increases the risk of endometrial hyperplasia and cancer. The risk endometrial cancer is associated with the amount of unopposed oestrogen the endometrium is exposed to during the patient’s life. Situations where there is increased exposure of unopposed oestrogen are:

  • Increased age
  • Earlier onset of menstruation
  • Late menopause
  • Oestrogen only hormone replacement therapy
  • No or fewer pregnancies
  • Obesity
  • Polycystic ovarian syndrome
  • Tamoxifen

 

Polycystic ovarian syndrome leads to increased exposure to unopposed oestrogen due to a lack of ovulation. Usually, when ovulation occurs, a corpus luteum is formed in the ovaries from the ruptured follicle that released the egg. It is this corpus luteum that produces progesterone, providing endometrial protection during the luteal phase of the menstrual cycle (the second half of the menstrual cycle). Women with polycystic ovarian syndrome are less likely to ovulate and form a corpus luteum. Without developing a corpus luteum during the menstrual cycle, progesterone is not produced, and the endometrial lining has more exposure to unopposed oestrogen. For endometrial protection, women with PCOS should have one of:

  • The combined contraceptive pill
  • An intrauterine system (e.g. Mirena coil)
  • Cyclical progestogens to induce a withdrawal bleed.

 

Obesity is a crucial risk factor because adipose tissue (fat) is a source of oestrogen. Adipose tissue is the primary source of oestrogen in postmenopausal women. Adipose tissue contains aromatase, which is an enzyme that converts androgens such as testosterone into oestrogen. Androgens are produced mainly by the adrenal glands. In women with more adipose tissue, and therefore more aromatase enzyme, more of these androgens are converted to oestrogen. This extra oestrogen is unopposed in women that are not ovulating (e.g. PCOS or postmenopause), because there is no corpus luteum to produce progesterone.

 

Tamoxifen has an anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer.

 

Additional risk factors not related to unopposed oestrogen are:

  • Type 2 diabetes
  • Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome

 

Type 2 diabetes may increase the risk of endometrial cancer due to the increased production of insulin. Insulin may stimulate the endometrial cells and increase the risk of endometrial hyperplasia and cancer. PCOS is also associated with insulin resistance and increased insulin production. Insulin resistance further adds to the risk of endometrial cancer in women with PCOS.

 

Protective Factors

Protective factors against endometrial cancer include:

  • Combined contraceptive pill
  • Mirena coil
  • Increased pregnancies
  • Cigarette smoking

Smoking appears to be protective against endometrial cancer in postmenopausal women by being anti-oestrogenic. Interestingly, it is not protective against other oestrogen dependent cancers, such as breast cancer (where it increases the risk). Smoking may have anti-oestrogenic effects in several ways:

  • Oestrogen may be metabolised differently in smokers
  • Smokers tend to be leaner, meaning they have less adipose tissue and aromatase enzyme
  • Smoking destroys oocytes (eggs), resulting in an earlier menopause

 

Presentation

The number one presenting symptom of endometrial cancer to remember for your exams is postmenopausal bleeding.

Endometrial cancer may also present with:

  • Postcoital bleeding
  • Intermenstrual bleeding
  • Unusually heavy menstrual bleeding
  • Abnormal vaginal discharge
  • Haematuria
  • Anaemia
  • Raised platelet count

 

Referral Criteria

It is worth being familiar with the NICE “suspected cancer: recognition and referral” guidelines (2015) concerning all common cancers. The guidelines contain the referral criteria and red flags for each type of cancer, and will help you quickly recognise or exclude red flag criteria.

The referral criteria for a 2-week-wait urgent cancer referral for endometrial cancer is:

  • Postmenopausal bleeding (more than 12 months after the last menstrual period)

 

NICE also recommends referral for a transvaginal ultrasound in women over 55 years with:

  • Unexplained vaginal discharge
  • Visible haematuria plus raised platelets, anaemia or elevated glucose levels

 

Investigations

There are three investigations to remember for diagnosing and excluding endometrial cancer:

  • Transvaginal ultrasound for endometrial thickness (normal is less than 4mm post-menopause)
  • Pipelle biopsy, which is highly sensitive for endometrial cancer making it useful for excluding cancer
  • Hysteroscopy with endometrial biopsy

pipelle biopsy can be taken in the outpatient clinic. It involves a speculum examination and inserting a thin tube (pipelle) through the cervix into the uterus. This small tube fills with a sample of endometrial tissue that can be examined for signs of endometrial hyperplasia or cancer. Pipelle biopsy is a quicker and less invasive alternative to hysteroscopy for excluding cancer in lower-risk women.

Depending on local guidelines, a normal transvaginal ultrasound (endometrial thickness < 4mm) and normal pipelle biopsy are sufficient to demonstrate a very low risk of endometrial cancer and discharge the patient.

 

Stages

The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage endometrial cancer:

  • Stage 1: Confined to the uterus
  • Stage 2: Invades the cervix
  • Stage 3: Invades the ovaries, fallopian tubes, vagina or lymph nodes
  • Stage 4: Invades bladder, rectum or beyond the pelvis

 

Management

The usual treatment for stage 1 and 2 endometrial cancer is a total abdominal hysterectomy with bilateral salpingo-oophorectomy, also known as a TAH and BSO (removal of uterus, cervix and adnexa).

Other treatment options depending on the individual presentation include:

  • A radical hysterectomy involves also removing the pelvic lymph nodes, surrounding tissues and top of the vagina
  • Radiotherapy
  • Chemotherapy
  • Progesterone may be used as a hormonal treatment to slow the progression of the cancer

 

Last updated July 2020
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