Section A
by Dr. S. Trompoukis, Gynecologist

Introduction

Endometrial (uterine, or womb) cancer is the most commonly occurring cancer of the female reproductive system. It is the 4th most common cancer that affects women after breast cancer, lung cancer and cancer of the colon and rectum. It is also the seventh leading cause of death from malignancy in women. Uterine cancer is more common in post-menopause women, and most cases are diagnosed in women aged over 50.

 

Etiology

The risk of developing uterine cancer increases with age, as 80% of cases occur in postmenopausal women, but there is an approximately 5% of women diagnosed before the age of 40 (mean age of diagnosis is 56 years). A hormone imbalance (unopposed or high levels of estrogen), is linked with the risk of developing uterine cancer. Conditions that may cause such imbalance include obesity, polycystic ovarian syndrome, diabetes, estrogen secreting tumors, late menopause and nulliparity.

Women treated with tamoxifen (for breast cancer) have an increased risk of endometrial cancer. Some reports suggest that women taking tamoxifen develop uterine sarcomas with greater frequency.

Family history of uterine cancer is also a known risk factor, as is previous pelvic radiotherapy.

There is also an increase to the incidence, associated with the history of other malignancies, such as breast cancer, ovarian cancer and colon cancer (especially Hereditary Non-Polyposis Colon Cancer HNPCC).

 

Endometrial cancer types

Uterine cancer usually starts in the lining of the womb. In the majority of cases (75-80%) a cancer called endometrioid adenocarcinoma is diagnosed, usually well differentiated, which has a relatively good prognosis.

A cancer called serous carcinoma represents about 10% of cases. It is an aggressive tumor, which usually invades the myometrium. Lymph node spread and recurrence is common.

Sarcomas (tumors started in the uterine muscles) are more rare (about 4%).

 

Endometrial cancer symptoms

In most cases, uterine cancer presents early with abnormal bleeding from the vagina (80% of cases), or heavy discharge. In postmenopausal women, any bleeding will be unusual. In younger women, irregular bleeding may consist of heavier than normal periods, or any bleeding between her periods. The duration or amount of bleeding does not make any difference. It is also important to remember that the normal bleeding pattern during the perimenopausal or perimenopausal period should become lighter and further apart. Any other bleeding should be properly evaluated.

Other signs and symptoms include uterine enlargement, pelvic pressure and pain in the lower abdomen. In more advanced stages, it may cause tiredness and loss of appetite.

Any postmenopausal bleeding should be assumed to be uterine cancer until proved otherwise.

 

Grades of Endometrial cancer

Histologic differentiation is very important. There are three categories:

  1. Highly differentiated
  2. Differentiated with partly solid areas
  3. Predominantly solid/undifferentiated

A highly differentiated carcinoma has better prognosis.

The diagnosis of endometrial hyperplasia may also be very important. Four categories are present:

  • Simple hyperplasia (SH)
  • Complex hyperplasia (CH)
  • Simple atypical hyperplasia (SAH)
  • Complex atypical hyperplasia (CAH)

The possibility of CAH to progress to carcinoma is about 29%.

 

Endometrial cancer diagnosis

Postmenopausal or irregular bleeding needs investigation. This must include a physical examination, and a transvaginal ultrasound scan to evaluate the size of the uterus and the endometrial thickness. A thick endometrium does not necessarily imply endometrial cancer and may be caused by other different factors (obesity, diabetes, hormonal therapy, whether postmenopausal or not, etc)

In some cases, a woman should have a more invasive examination with an endometrial biopsy (dilatation and curettage) to confirm or exclude the diagnosis. This biopsy can be carried out with a small flexible tube, under general anesthesia, on an outpatient basis. The tissue is then sent for histological evaluation to a laboratory.

In some cases, a gynecologist may carry out a hysteroscopy before the biopsy. Blood tumor markers are not reliable for the diagnosis of endometrial cancer. If the CA-125 is elevated, imaging studies should be performed.

 

Staging of endometrial cancer

If a woman is diagnosed with uterine cancer, further tests are recommended in order to define the stage of the cancer. Staging is the process of classifying a tumor according to whether or not it has spread, in order to decide the best treatment options.

These tests may include:

  • Chest X-ray:  to see if uterine cancer has spread to the lungs.
  • CT scan or MRI scan:  to check if the cancer has spread to the chest, abdomen and pelvis.

Staging helps doctors to decide the best treatment options. Uterine cancer has four (4) stages:

  • Stage 1:  The cancer is confined to the body of the uterus
  • Stage 2:  The cancer has spread to the cervix, but not extending beyond the uterus
  • Stage 3:  The cancer has spread outside the uterus, but not outside the pelvis
  • Stage 4:  The cancer has spread into other organs, such as the bladder, bowel, liver or lungs

This is a simplified guide. Each stage is divided into further categories.

 

Endometrial cancer treatment

A careful medical history and a physical examination should help the doctor decide if the woman is a surgical candidate or not.

  • Surgery Uterine cancer treatment usually includes surgery. Since most of the cases will present at stage 1, the basic treatment is to remove the uterus, both ovaries and the fallopian tubes. Samples from the lymph nodes may also be taken. If the cervix shows any signs of invasion, the woman may have a radical hysterectomy, which involves removal of the uterus, the upper half of vagina and the pelvic lymph nodes. In case of advanced uterine cancer, the surgeon will try to remove as much of it as possible. This is known as debulking surgery, which will not cure the cancer, but may ease some of the symptoms.
  • Chemotherapy: Chemotherapy is used after surgery to destroy any remaining cancer cells and reduce the risk of cancer returning. In case of advanced uterine cancer, chemotherapy has mostly palliative role, in order to relieve the symptoms.
  • Radiotherapy: Internal or external radiation therapy may be used after surgery to prevent vault recurrence, or if there is evidence of lymph node involvement. It may also be used in women who are unsuitable for surgery, to slow tumors growth. Combined chemotherapy and radiotherapy is an option in certain cases, following surgery.
  • Hormone therapy: Hormone therapy can be used prior to surgery, or in advanced stages. Its main use is to treat recurrent disease, in order to reduce the symptoms. In some cases of younger women who wish to have children, and under very specific circumstances, hormone therapy may be used for treatment of uterine cancer.

 

Endometrial cancer prognosis

In the 75% of cases, the tumor at the time of diagnosis is confined to the body of the uterus, and because of that, the survival rate is 75% or even higher. The prognosis as always depends on the stage and the 5-year survival rates are generally estimated as follows:

  • Stage 1: 81%
  • Stage 2: 69%
  • Stage 3: 51%
  • Stage 4: 16%

Many factors may affect a patient’s prognosis, such as her general health and the way she responds to treatment.

 

Endometrial cancer prevention

It is not always possible to prevent uterine cancer, but there are some ways to reduce the risk. Women should avoid becoming overweight, by maintaining healthy diet habits. They should also exercise frequently.

Long-term use of some types of contraception may also help to reduce the risk of uterine cancer. Regimens containing estrogen and progesterone will help preventing endometrial hyperplasia and subsequent carcinomas. Only women who have had hysterectomies should be prescribed estrogen pills.

Women taking tamoxifen should have frequent endometrium ultrasound scans. They should also report any case of abnormal bleeding to their gynecologist for a proper evaluation.

 

Section B
by Dr. M. Tsiatas, Medical Oncologist

Risk factors in endometrial cancer

Treatment strategy depends upon certain factors which define the risk of recurrence in endometrial cancer. These factors include: grade(aggressiveness), invasion of the myometrium, extension (spread outside of the uterus), histology (serous or clear cell), involvement of the blood or lymphatic vessels and older age.

  • Low risk: The cancer is confined to the endometrium, provided it is not of serous or clear cell type.
  • Intermediate risk: The cancer is not serous or clear cell type, has invaded the myometrium, or has microscopic involvement of the cervix. In case of lymphovascular invasion, outer-third myometrial invasion, and high tumor grade, the risk is upgraded to intermediate-high.
  • High risk: The cancer involves the cervix at the time of surgery, the pelvis, tissue outside the pelvis, or is of serous or clear cell type.

 

Treatment options in endometrial cancer

Treatment for endometrial cancer depends on the risk for recurrent disease after surgical therapy:

 

Low-risk disease

The risk of relapse after surgery for low-risk endometrial cancer is very low, with estimates placed at 5% or less. Therefore, no further treatment is recommended.

 

Intermediate-risk disease

Women with low-intermediate risk for relapse may need no further treatment since their risk of relapse after surgery alone is low (5% or less). Women with high-intermediate risk benefit from adjuvant therapy. For most women with intermediate-risk disease, adjuvant vaginal or external beam radiation therapy is given in an effort to minimize the recurrence rate.

 

High-risk disease

Women with high-risk endometrial cancer will need adjuvant chemotherapy, especially if the disease is located outside of the uterus. Most oncologists recommend adjuvant radiation with or without chemotherapy, if high-risk disease is confined to the uterus.

 

Types of adjuvant treatment

 

Radiation therapy

Radiation therapy refers to the use of high-energy x-rays to slow or stop the growth of cancer cells.  For patients with endometrial cancer, adjuvant radiation is given to minimize the risk of the cancer recurrence after main treatment (usually surgery).

Radiotherapy is given either as vaginal brachytherapy or as external beam radiation therapy.

 

Vaginal brachytherapy

Brachytherapy delivers radiation from a device that is temporarily placed inside the vagina.  There are two types of vaginal brachytherapy: low-dose rate and high-dose rate.

  • Low-dose rate brachytherapy delivers radiation through the vagina continuously for two or three days, 24 hours a day. Patients stay in the hospital during this treatment.
  • High-dose rate brachytherapy delivers radiation through the vagina, for only a few minutes at a time once a day, and is repeated 3 to 5 times on an outpatient basis.

 

External beam radiation therapy

External beam radiation therapy is given for a few seconds once per day, five days per week, for 5 to 6 weeks on an outpatient basis. 

 

Side effects of radiation therapy

Radiation can cause both short-term and long term side effects. The short term side effects may include:

  • Weakness
  • Discomfort with urination
  • Loose stools and frequent bowel movements
  • Temporary loss of pubic hair

Besides short-term side effects, which usually resolve after treatment is completed, there are also long-term side effects that may not appear until months later, after treatment is completed. These include:

  • Urine leakage
  • Bowel inflammation with pain, bloody stools and diarrhea
  • Narrowing or dryness of the vagina

 

Chemotherapy

Chemotherapy is a treatment given following surgery to stop the growth of remaining cancer cells. This type of chemotherapy is called "adjuvant". The purpose of this treatment is to decrease the chance of recurrence in any site of the body, with the final goal being to cure the patient. 

For localized disease, chemotherapy is given along with radiotherapy in different schedules.

For advanced disease, chemotherapy is given alone. The basis of chemotherapy is platinum and is usually used in combination with other agents mainly in advanced disease. 

 

Side effects of chemotherapy

The most common side effects of chemotherapy include:

  • Weakness
  • Hair loss
  • Nausea and vomiting
  • Diarrhea
  • Low blood counts
  • Renal impairment
  • Numbness and tingling of fingers and toes.

 

Special considerations

  • Endometrial cancer in young women: For young premenopausal women with endometrial cancer, at a time when they desire pregnancy and have a low risk of relapse, surgery (hysterectomy) may be delayed, except for patients with intermediate- or high-risk endometrial cancer. When surgery is delayed, progestin treatment is used to suppress the growth of the endometrial cancer. These patients still need definite surgical treatment following family planning.
  • Cancer in medically inoperable women: For women who are obese or who have other serious medical conditions and radical operation cannot be performed, more conservative surgery along with radiotherapy is an alternative approach.
  • Incompletely staged patients: For patients who for some reason did not complete staging, the risk for recurrence will be estimated based on the available information, in order to be treated accordingly. Certainly, operating again is an option. 

 

Follow-up after treatment

Most oncologists recommend close follow-up after the end of treatment, particularly in the first 3 years. It is usually advisable to have a gynecology exam and Pap smear every 4 to 6 months for several years. Other tests such as CT (computed tomography) scans of the abdomen or chest X-rays can be performed if recurrence is suspected.

Women are highly encouraged to discuss important issues like menopausal symptoms as well as sexual problems with their physicians.

 

Content on this site is not a substitute for professional medical advice. You should always consult your doctor.