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Endometrium

Each year, more than 300 women with endometrial, cervical, ovarian and other cancers of the female reproductive system receive treatment from Cleveland Clinic gynecologic oncologists, who collaborate closely with Cleveland Clinic gynecologic pathologists, medical and radiation oncologists, and radiologists.

Membership in the Gynecologic Oncology Group offers patients access to investigational treatments through more than 40 ongoing clinical trials. Additional studies offer patients access to the latest treatments under investigation.

The Clinic’s Familial Cancer Registry offers advice on appropriate screening and prevention to women with a genetic predisposition to ovarian and/or breast cancer, or who have been experiencing cancer symptoms.

What is Uterine Cancer?

Uterine cancer affects over 40,000 women in the United States each year and occurs in approximately 2% of US women during their lifetime. Approximately 7,000 of these women will die each year from this disease. There are two basic classes of uterine cancers:

Endometrial cancer makes up the majority of uterine cancers. This cancer arises from the tissue lining the inside of the uterus (womb). The exact cause of endometrial cancer is unknown, but prolonged exposure to estrogen is a known to increase the risk of this type of cancer. Estrogen increases the growth of the lining of the uterus while progestins block this growth. It is the balance between these two hormones that is important in the risk of endometrial cancer. Known risk factors for endometrial cancer are:

  • Age - As women get older, the likelihood of endometrial cancer increases. Most endometrial cancers occur in women age 40 and older.
  • Early menstruation or late menopause - If a woman began monthly periods before age 12 or ends monthly periods after age 50, the risk for endometrial cancer might increase because the uterus might be exposed to estrogen for more years.
  • Never having been pregnant - Increases the risk of endometrial cancer probably due to exposure of the uterus to estrogen for more years.
  • Use of tamoxifen - This drug, which is typically used to treat women with breast cancer, acts like estrogen in the uterus and can increase the risk of endometrial cancer.
  • Estrogen replacement therapy (ERT) - Estrogen is commonly used to treat the symptoms of menopause and if used alone (without progestins), can increase endometrial cancer risk. The combination of estrogen and progesterone for hormone replacement therapy (HRT) does not increase endometrial cancer risk.
  • Ovarian diseases - Certain ovarian tumors and polycystic ovaries can lead to higher than usual levels of estrogen for long periods of time and may increase the risk of endometrial cancer.
  • Obesity (being very overweight)- Fat tissue in the body can convert other hormones into estrogens. Women who are more than 50 pounds overweight may have a 10 times the risk for endometrial cancer.
  • A diet high in animal fat - A high-fat diet can increase the risk of several cancers, including endometrial cancer. Because fatty foods are also high-calorie foods, a high-fat diet can lead to obesity--another risk factor for endometrial cancer .
  • Diabetes - Diabetes has been linked to weight, but some studies suggest that diabetes by itself could be a risk factor for endometrial cancer.
  • Family history - Women with family histories of endometrial or colon cancer may carry an abnormal gene that increases the risk of these and other cancers.
  • Breast or ovarian cancer - Women who have had breast cancer or ovarian cancer might have an increased risk of having endometrial cancer.
  • Endometrial Hyperplasia - Overgrowth of the lining of the uterus from estrogen stimulation leads to precancerous changes known as hyperplasia. Up to 30% of women with certain types of hyperplasia may develop endometrial cancer.

Protective factors are multiple births, oral contraceptive use, and smoking.

Uterine sarcomas make up only 5-7% of uterine cancers. They arise from various tissues within the uterus and outcomes vary depending on the type. However, as a group uterine sarcomas tend to be more aggressive with a higher likelihood of early spread and recurrence than typically seen for endometrial cancers.

  • Leiomyosarcoma-Develops from the muscular wall of the uterus.
  • Carcinosarcoma (Malignant Mixed Mullerian Tumor)-Develops from the lining of the uterus.
  • Endometrial Stromal Sarcomas and adenosarcomas - Develops from the stroma or supporting layer just below the lining of the uterus.

The remainder of this section will focus on endometrial cancers.

What are the cancer symptoms?

Nearly 90% of women with endometrial cancer present with abnormal vaginal bleeding or abnormal vaginal discharge as a major cancer symptom. Typical endometrial cancer symptoms may include:

  • Vaginal bleeding between normal periods in pre-menopausal women
  • Vaginal bleeding or spotting in post-menopausal women
  • Extremely long, heavy, or frequent vaginal bleeding episodes in women over 40
  • Thin white or clear discharge in post-menopausal women
  • Lower abdominal pain or pelvic pain and cramping
  • Pain during urination or sexual intercourse

How is endometrial cancer diagnosed?

If a woman has any of the gynecologic cancer symptoms, she should visit her doctor. The doctor will ask her about her symptoms, risk factors, and medical history. A general physical exam and pelvic exam are typically performed when gynecologic cancer symptoms are present as well.

Additional procedures that might be used to help diagnose endometrial cancer are:

  • Endometrial biopsy - A very thin flexible tube is inserted into the uterus through the cervix (the mouth of the womb) to obtain a sample of endometrial tissue. This can usually be performed in the office.
  • Dilation and curettage (D & C)- A special surgical instrument is used to scrape tissue from inside the uterus and is usually done in the operating room. Endometrial tissue samples removed by biopsy or D & C are examined under a microscope to determine whether cancer is present or not.
  • Hysteroscopy - A hysteroscope (uterine scope) is hooked to a video camera and inserted through the cervix to look directly at the lining of the uterus and help guide biopsies.
  • Transvaginal ultrasound or sonography - A transvaginal sonogram uses sound waves to create images of the uterus so that the lining of the uterus can be measured.

Other tests that may be performed once a diagnosis of uterine cancer has been made are:

  • CT or CAT scan - This is a scan that involves taking series of detailed pictures of areas inside the body. The images are created by a computer linked to an X-ray machine.
  • MRI (also called magnetic resonance imaging)- Radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body.
  • CA-125 assay - This blood test has been used mostly in ovarian cancer. However, some women with endometrial cancer may also have abnormal levels of this protein in blood or other body fluids.

What are the stages of endometrial cancer?

One of the biggest concerns about a cancer diagnosis is whether the cancer has spread (metastasized) beyond its original location. To determine this, the doctor assigns a number (0 through IV) to the diagnosis. The higher the number, the more the cancer has spread throughout the body. This is called "staging."
The stages of endometrial cancer include the following:

  • Stage I: The cancer is confined to the uterus, either in the endometrium or in the myometrium (the muscle of the uterus). Up to 75% of women with endometrial cancer will be assigned to stage I.
  • Stage II: The cancer involves the cervix.
  • Stage III: At this stage, the cancer has moved outside the uterus and cervix into one of the following areas: the peritoneum (a membrane around the inside of the abdomen), fallopian tubes, ovaries, pelvic or para-aortic lymph nodes, vagina or abnormal cells in the abdominal cavity.
  • Stage IV: The cancer has moved outside the pelvis to other areas of the body, including the bladder, the bowel, or to the lymph nodes in the groin.

What is the grade of endometrial cancer?

The grade is assigned by the pathologist and tells how much the tumor looks like normal endometrial tissue. Endometrial cancers are graded 1 to 3 with a higher risk of spread outside of the uterus and recurrence with a higher grade tumor.

  • Grade 1: Well differentiated and looks similar to normal endometrial tissue but has more endometrial glands and some abnormal looking cells. These tend to be slow-growing with a lower risk of spread outside of the uterus.
  • Grade 2: Moderately differentiated and has more solid areas.
  • Grade 3: Poorly differentiated with more than half of the tumor being solid with very abnormal looking cells.

How is endometrial cancer treated?

Surgery is the main treatment for most women with endometrial cancer nd is required for proper staging. Radiation therapy, hormone therapy, and chemotherapy are other options for treatment. In certain situations, a combination of treatments might be used. The choice of treatment or treatments will depend on the type and stage of the cancer and the overall medical condition of the patient.

Surgery

For most patients with endometrial cancer treatment begins with surgical staging.

  • Hysterectomy: removal of the uterus and cervix. This procedure can be done in the traditional manner (through an incision in the abdomen), through the vagina, or laparoscopically (through a small incision, using a laparoscope).
  • Salpingo-oophorectomy: removal of the ovaries and fallopian tubes (the tubes through which the fertilized egg travels from the ovaries to the uterus)
  • Lymphadenectomy: Lymph nodes in the pelvis and lower abdomen may be removed to see if there has been spread to these structures.
  • Radical hysterectomy: a more extensive type of hysterectomy with removal of the uterus, cervix, ligaments attached to the cervix and uterus and part of the vagina and tissue attached to the uterus and cervix. Salpingo-oophorectomy and lymphadenectomy are usually also performed when this procedure is done for endometrial cancer.
  • Debulking: removal of any tumor that is found outside of the uterus at the time of surgery.
  • Omentectomy: Removal of a portion of a fatty apron that is attached to the large intestines in the upper abdomen.
Radiation Therapy

High levels of radiation are used to kill cancer cells and prevent them from multiplying, while minimizing damage to healthy cells. The radiation may be delivered by special equipment that can send radiation from outside of the body into the pelvis (teletherapy or external radiation) or from a device placed into the uterus or vagina that can deliver radiation directly into the tumor (brachytherapy or internal radiation). Radiation therapy as the primary mode of therapy (without surgery) is reserved for those patients that have multiple medical problems and are considered too ill to undergo abdominal surgery.

Some patients will be found to have intermediate or high-risk for recurrence following pathologic review of their surgical specimens. Your physician may offer you internal vaginal radiation to decrease the chance of a recurrence at the top of the vagina. Alternatively, you may be offered external pelvic radiation to decrease the risk of recurrence in the pelvis or at the top of the vagina.

Chemotherapy

Chemotherapy is sometimes used for the treatment of endometrial cancers and is given to kill or slow the growth of cancer cells. Patients that are offered chemotherapy usually include those with spread of cancer to the lymph nodes, spread outside of the pelvis, clear cell or papillary serous types of endometrial cancer, or patients with recurrence of their cancer. A wide variety of chemotherapy regimens can be used in this setting and may be given in addition to or in place of radiation therapy.

Hormonal Therapy

Occasionally patients with advanced stage disease or early spread of tumor will be treated by hormonal therapy. Most commonly this is done with progestins, a female hormone that helps block growth of the endometrial cells. Drugs that block the binding or production of estrogen can also be used alone or in combination with progesterone. Tumors of lower grade tend to respond better to hormonal therapy than high-grade tumors. However, excellent responses have been seen in patients with all grades of endometrial cancer.

How is it followed after treatment?

Patients are typically followed with surveillance exams after treatment. Current recommendations are for History and physical exam with or without pap smears every 3-6 months for the first 2 years, then every 6-12 months. CA-125, a blood test commonly used in ovarian cancer follow-up, is sometimes used to screen for recurrent disease in high-risk patients. Chest Xray may be performed 1-2 times per year. Additionally, should watch for signs of recurrence such as vaginal bleeding, new or persistent abdominal pain or bloating, nausea, vomiting, persistent cough, and increasing back pain. Patients with these symptoms should notify there doctor.

Can endometrial cancer be prevented?

Most cases of endometrial cancer cannot be prevented. Women can take some measures to reduce their risk of developing endometrial cancer by using oral contraceptives and controlling obesity and diabetes.

In addition, women who are considering estrogen replacement therapy should talk to their doctors to assess their risk of endometrial cancer.

The American Cancer Society encourages women to discuss any unexpected bleeding or spotting to their doctors. Women who have or are at high risk for hereditary nonpolyposis colon cancer (HNPCC) should receive annual screenings for endometrial cancer with and possibly ultrasound or endometrial biopsy starting at age 35.