Endometrial cancer

Endometrial cancer, also known as cancer of the body of the uterus, is a common malignancy of woman’s reproductive organ that develops in the mucosa lining the inner part of the uterine body. The uterus is made of smooth muscle tissue. It consists of the uterine body which is located inside the pelvis and is the location where pregnancy develops. The cervix uteri is located partially in the vagina and its role is to hold the developing pregnancy inside the uterus by tightly closing the cervical canal. The main role of the uterine body is to hold the growing foetus and make it develop. The inner surface of the uterine body is covered by a special mucous membrane known as endometrium. It undergoes regular changes that cause regular menstrual bleeding; these changes manifest the preparation of the endometrium for an embryo to implant if conception occurred.

It is in the endometrium that cancer develops. Endometrium lines the cavity of the cervix turning smoothly into the cervical canal mucosa or endocervix.

Endometrial cancer is the second most prevalent malignancy of female reproductive organs worldwide, following cervical cancer. Approximately 290,000 women are diagnosed for EC, and 74,000 die due to that disease. Most EC cases are recorded in highly developed countries, where it is ranked the fourth most common cancer type in women (following breast cancer, lung cancer and skin cancer) and the most frequent cancer of the reproductive organs. The peak incidence is between 55 and 59 years of age. In 2010, in Poland, approx. 5,125 women were diagnosed with cancer of the endometrium; 2,042 died due to that disease. The incidence is slowly but constantly growing.

That type of cancer displays quite early some characteristic symptoms: spotting and bleeding from birth canals. As it occurs mostly after menopause, that symptom usually raises concerns of patients and make them see a doctor. For that reason, most EC cases is detected at an early stage with a full chance for recovery. Sometimes, however, the disease manifests only in the advanced stage by metastases to the other organs of the abdominal cavity and lymph nodes.

It is recognised that owing to transvaginal ultrasonography abnormal endometrium can be detected to begin early diagnostics. Therefore, regular gynaecological check-ups allow early detection of EC, even at an premalignant stage.

Endometrial cancer is caused by excessive stimulation of the endometrium without being counteracted by the activity of progestogens. The risk factors include: obesity, high blood pressure, diabetes, infertility or single childbirth, hormonal disorders caused by active ovary tumours, long menstruation period, treatment by tamoxifen and Lynch syndrome (in the latter case, the risk is 30–60% throughout the lifespan). The risk is reduced when using two-component oral hormonal contraceptives.

The most significant diagnostic procedure for EC is the so-called silation and curettage (D&C):

the procedure involves scraping a layer of endometrial cells for histopathological examination. It is performed in general anaesthesia. It should be stressed that the procedure does not leave and surgical scars, as it is performed through natural orifices of the body, ans the patient leaves hospital after three-four hours, usually without any health issues. Another increasingly used diagnostic procedure is hysteroscopy involving the introduction of a miniature camera into the uterus to see the endometrium in a large zoom and collect targeted specimens.

No less important is a gynaecological exam performed by a gynaecological oncologist. It is made by a speculum inserted through the vagina or rectum. Gynaecological exam allows to assess possibilities of surgery and stage of the disease.

Additionally, pulmonary X-ray and abdominal and pelvic CT are done as a standard to exclude metastases to the other organs. In selected cases, MRI of the reproductive organ is performed.

Basic blood tests to assess the performance of bone marrow, kidneys and liver are certainly obligatory.

Due to early symptoms of EC, most cases are detected at an early stage with a high chance for recovery and five-year survival ranging from 80 to 90%. In advanced cases, prognosis is much worse, and more aggressive treatment is needed with survival rate of 30–50%. It is of utmost importance that treatment of diagnosed EC is carried out in a specialised oncology centre. This increases the chance for recovery, in particular, owing to correct diagnosis and properly adapted therapy.

Treatment method depends on the cancer stage at diagnosis. The basic method is surgery that consists in the removal of the uterus along with surrounding tissue. In certain clinical cases, pelvic, paraaortic or greater omentum lymph nodes may also be dissected. In very advanced cases, the procedure is aimed to remove the whole cancerous tissue from the abdominal cavity (maximum cytoreduction).

In non-operable cases, radiotherapy, hormonal therapy or chemotherapy are used. Radiotherapy involves directing a beam of ionising radiation on the tumour and its surrounding tissue to destroy dividing cells, such as cancerous cells. Radiation is generated in specialised medical device, so-called accelerators, or is produced by specially prepared radioactive elements. Radiation therapy of endometrial cancer usually consists of two stages: radiation of the tumour ‘from outside’ (using an accelerator, through the skin and health tissue surrounding the tumour), and from inside by placing a radioactive element inside the tumour (in the cervical cavity) which does not damage healthy tissue around the tumour.

Many EC patients being elderly and suffering from cardiovascular and respiratory diseases, surgical treatment is often contraindicated even at early stages. Stand-alone brachytherapy may then prove to be an effective option. Radiation dose is limited by the so-called normal tissue tolerance as a sort of compromise between damaging the tumour and conserving normal tissue that surround it. Organs such as the bladder or rectum are sensitive to radiation and may be damaged by too high a dose. Nowadays, radiotherapy is a very complicated treatment method using state-of-the-art medical devices and computers.

Radiotherapy is also applicable as an additional treatment after surgery, known as adjuvant treatment. After the removal of the tumour, the pelvis minor, where the involves uterus is located, is irradiated to destroy singular, invisible cancer cells.

Chemotherapy – involves the administration (usually, intravenously intravenously or through a catheter) of a strong medicine that damages cancer cells. Typical side effects include nausea, weakening of the bone marrow, hair fall-out and other symptoms which usually disappear after treatment. Chemotherapy is usually delivered in six courses every 3–4 weeks.

Hormonal therapy is the administration (either orally or via injection) of gestagenic hormones which effectively inhibit the development of EC. Such treatment is usually well tolerated, although it raises the risk of venous thrombosis and leads to the increase of body mass.

In the case of endometrial cancer with metastases to other organs, gestagenic hormonal therapy or chemotherapy is typically applied depending on the age, general health status, clinical picture and course of disease.

Radiotherapy of EC is well tolerated. Adverse effects may appear both during radiotherapy and many months or even years afterwards. The most common side effects are general weakness and skin changes at the irradiated site. Detailed list of side effects:

During and immediately after (up to 3 months) radiotherapy:

Frequent:

• redness of the skin at the irradiated site,
• loss of hair at the irradiated site,
• redness in the crotch region,
• vaginal dryness, burning sensation, vaginal discharges
• menstrual disorders,
• pain in the abdomen,
• bloated feeling,
• nausea, vomiting (rarely),
• lack of appetite,
• pain in the rectal region,
• defecation disorders – diarrhoea, bloating, increased amount of gases, mucosa in the, pain while emptying the bowels,
• urinary disorders – feeling of bladder pressure, more frequent urination, painful urination,
• general weakness,
• fatigue.

Rare:

• blood in the stool,
• blood in the urine,
• bleeding from the vagina,
• mucosal peeling in the crotch region.

Long after radiotherapy (more than three months):

Frequent:

• reduced bladder volume – more frequent urination,
• persisting defecation disorders – more frequent defecation or bloating
• vaginal dryness, vaginal discharge,
• bloodstained vaginal mucosa after sexual intercourse,
• discomfort, pain when having sexual intercourse,
• no desire of sexual contacts,
• infertility.
• symptoms of menopause,
• fatigue,
• skeletal pain in the pelvis.

Rare:

• cystitis
• bladder necrosis
• persistent bladder bleeding
• rectal bleeding
• intestinal obstruction
• fistulas: intestinal, rectal/vesical, rectal/vaginal, vesical/vaginal
• discolouring of the skin at the irradiated site
• feeling of dry skin

Patients from the high risk group (stage > IB, G3 and squamous-cell carcinoma, clear cell carcinoma, papillary serous carcinoma or sarcoma, status after radiotherapy) require strict follow-up after radical surgery. If recurrence is suspected, full diagnostics should be done to prepare a plan for further treatment.

Follow-up in that group should be carried out every four months over two tears following treatment, then every six months for up to five years. Imaging and laboratory testing should be done subject to specific indications.