Endometrial cancer

Endometrial cancer is the cancer of the endometrial lining of the uterine corpus. There are multiple histological types, but the most common is the endometroid carcinoma. It’s mostly a disease of postmenopausal women.

It’s the most common form of gynaecological cancer (but not the most deadly, ovarian cancer is). It causes symptoms early, enabling diagnosis at a stage where there is a high likelihood of cure. The mortality is relatively low.

We can distinguish type I and type II endometrial cancer. Compared to type II tumours, type I tumours have a favourable prognosis, are oestrogen-induced, responsive to progestins, and may be preceded by an intraepithelial neoplasm.

Risk factors

The risk factors for type I and type II are different. Type I is generally related to increased unopposed oestrogen exposure, while type II is unrelated to oestrogen:

• Type I tumours
  • Obesity
  • Unopposed oestrogen therapy
  • Tamoxifen
  • PCOS
  • Early menarche
  • Late menopause
• Type II tumours
  • Old age
  • Low BMI
  • Non-white ethnicity

Pathology

These are most common histological types:

• Endometrioid type (80%)
• Non-endometrioid type
  • Serous adenocarcinoma
  • Clear cell carcinoma
  • Mucinous adenocarcinoma
  • +++

However, we can also distinguish two types based on the incidence, responsiveness to hormones, and clinical behaviour:

• Type I tumours – 80% of cases
  • Endometrioid carcinoma grade 1
  • Endometrioid carcinoma grade 2
• Type II tumours
  • Endometrioid carcinoma grade 3
  • Non-endometrioid carcinomas

Compared to type II tumours, type I tumours have a favourable prognosis, are oestrogen-induced, responsive to progestins, and may be preceded by an intraepithelial neoplasm.

Clinical features

The characteristic symptom is abnormal uterine bleeding, which is the presenting complaint in almost all cases. There is often metrorrhagia or hypermenorrhoea.

Diagnosis and evaluation

As always, history and physical examination is important. History should evaluate if the patient has received unopposed oestrogen therapy, if there is family history of gynaecological cancer, etc. Physical examination should include a conventional gynaecological exam, as well as a rectovaginal examination, to assess the rectovaginal septum. This can give information on whether the cancer has spread regionally.

Imaging is important. Transvaginal ultrasound can be used to evaluate the endometrial thickness. A thickness of ≤4 mm in postmenopausal women means a very low risk for endometrial cancer.

The gold standard for abnormal postmenopausal bleeding is fractional dilatation and curretage, which allows for histological examination. One may also perform an endometrial biopsy, or hysterectomy specimen. The endometrial biopsy may be blind or guided by hysteroscopy.

Staging

MRi or CT is important in staging the tumour, to evaluate the local and distant spread. The complete staging can only be performed after total hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy.

FIGO classification

The International Federation of Gynaecology and Obstetrics (FIGO) classifications are similar to the TNM, but slightly different. FIGO classifications are preferred in gynaecology.

Stage	Description
0	Carcinoma in situ
I	Tumour is localised to the corpus
II	Tumour reaches the cervix
III	Tumour infiltrates the neighbouring tissues (adnexa, vagina, lymph nodes)
IVa	Tumour infiltrates the bladder or rectum
IVb	Distant metastasis

(There are substages of I, II, and III, but I’ve excluded them for simplicity)

Management

Unless contraindicated, surgical therapy should always be part of the therapy of endometrial cancer. If surgery is contraindicated, primary combined irradiation, brachytherapy, and teletherapy are necessary. Preoperative and/or postoperative irradiation may be performed as well.

Surgical therapy

Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy (BSO) is the mainstay of surgical treatment. It is curative in early stages and improves prognosis in later stages. It also allows the proper surgical staging. Laparoscopy is preferred over laparotomy.

Pelvic and para-aortic lymph nodes are removed in case of middle risk and high risk stages, generally IIIc and above.

If presurgical evaluation shows possible spreading to the cervix (stage II), a radical hysterectomy is performed instead. Radical hysterectomy means the en bloc removal of the uterus, cervix, upper vagina, and parametrium.

Hormonal therapy

It was theorised that because Type I endometrial cancer is hormone sensitive that progestins may reduce tumour growth, but a large meta-analysis found no survival benefit for progestins. Hormonal therapy is therefore not routinely recommended but is an option for those with low-risk endometrial cancer who wish to preserve fertility.

Radiotherapy

Endometrial cancer is not particularly radiosensitive (especially compared with cervical cancer). Radiotherapy may be used for inoperable patients or for palliation. Both external beam radiotherapy and intravaginal brachytherapy may be used.

Chemotherapy

Chemotherapy is not frequently used in endometrial cancer. It may be used in recurring cancer or as adjuvant therapy. Paclitaxel + carboplatin is used.

Follow-up after treatment

• Physical examination
  • Every 3 months in the first year
  • Every 4 months in the second year
  • Then less and less frequently until 1 time per year
• Imaging
  • Chest x-ray
  • MRI/CT/transvaginal ultrasound
• CA-125 detection