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Cancer of the Uterus

(Endometrial Cancer; Uterine Cancer)

By Pedro T. Ramirez, MD, Professor, Department of Gynecologic Oncology and Reproductive Medicine, David M. Gershenson Distinguished Professor in Ovarian Cancer Research, and Director of Minimally Invasive Surgical Research and Education, The University of Texas MD Anderson Cancer Center
Gloria Salvo, MD, Rotating Research Resident, Department of Gynecologic Oncology and Reproductive Medicine, MD Anderson Cancer Center

Cancer of the uterus develops in the lining of the uterus (endometrium) and is thus also called endometrial cancer.

  • Endometrial cancer usually affects women after menopause.

  • It sometimes causes abnormal vaginal bleeding.

  • To diagnose this cancer, doctors remove a sample of tissue from the endometrium to be analyzed (biopsy).

  • Usually, the uterus, ovaries, and fallopian tubes and sometimes the nearby lymph nodes are removed, often followed by radiation therapy and sometimes by chemotherapy.

Most cancers of the uterus begin in the lining of the uterus (endometrium) and are more precisely termed endometrial cancer (carcinoma). In the United States, it is the most common gynecologic cancer and the fourth most common cancer among women. One in 35 women gets endometrial cancer. This cancer usually develops after menopause, most often in women aged 50 to 60. Over 90% of cases occur in women over 50.

More than 80% of endometrial cancers are adenocarcinomas, which develop from gland cells. Fewer than 5% of cancers in the uterus are sarcomas. Sarcomas develop from connective tissue and tend to be more aggressive.

There are two types of endometrial adenocarcinomas:

  • Type I cancers are more common, respond to estrogen, and are not very aggressive. They tend to occur in younger or obese women or in women going through perimenopause (the years just before and the year after the last menstrual period).

  • Type II cancers are more aggressive and tend to occur in older women. About 10% of endometrial cancers are type II.

Causes

Endometrial cancer is more common in developed countries where the diet is high in fat.

The most important risk factors for endometrial cancer are

  • Age over 50

  • Conditions that result in a high level of estrogen but not progesterone

  • Obesity

  • Diabetes

Other risk factors for endometrial cancer include the following:

  • Having had or having a family member who has had cancer of the breast, ovaries, or possibly the large intestine (colon) or lining of the uterus

  • Having had radiation therapy directed at the pelvis

  • Using tamoxifen for 5 years or longer

  • Having high blood pressure

Conditions that result in a high level of estrogen but not progesterone include the following:

  • Starting menstrual periods (menarche) early, reaching menopause after age 52, or both

  • Having menstrual problems related to release of the egg (ovulation), usually with symptoms such as excessive bleeding during periods, spotting between periods, or long intervals without periods

  • Not having any children

  • Having tumors that produce estrogen

  • Taking drugs that contain estrogen, such as estrogen therapy without a progestin (a synthetic drug similar to the hormone progesterone), after menopause

Estrogen promotes the growth of tissue and rapid cell division in the lining of the uterus (endometrium). Progesterone helps balance the effects of estrogen. Levels of estrogen are high during part of the menstrual cycle. Thus, having more menstrual periods during a lifetime may increase the risk of endometrial cancer. Tamoxifen, a drug used to treat breast cancer, blocks the effects of estrogen in the breast, but it has the same effects as estrogen in the uterus. Thus, this drug may increase the risk of endometrial cancer. Taking oral contraceptives that contain estrogen and a progestin appears to reduce the risk of endometrial cancer.

In about 5% of women with endometrial cancer, heredity plays a role. About half of the cases that involve heredity occur in women who have or who have relatives who have a hereditary form of colon cancer called Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Symptoms

Abnormal bleeding from the vagina is the most common early symptom of endometrial cancer. Abnormal bleeding includes

  • Bleeding after menopause

  • Bleeding between menstrual periods

  • Periods that are irregular, heavy, or longer than normal

One of three women with vaginal bleeding after menopause has endometrial cancer. Women who have vaginal bleeding after menopause should see a doctor promptly. A watery, blood-tinged discharge may also occur. Postmenopausal women may have a vaginal discharge for several weeks or months, followed by vaginal bleeding.

Diagnosis

  • Biopsy

  • Sometimes dilation and curettage with hysteroscopy

Doctors may suspect endometrial cancer if women have typical symptoms or if results of a Papanicolaou (Pap) test, usually done as part of a routine examination, are abnormal. If cancer is suspected, doctors take a sample of tissue from the endometrium (endometrial biopsy) in their office and send it to a laboratory for analysis. An endometrial biopsy accurately detects endometrial cancer more than 90% of the time.

If the diagnosis is still uncertain, doctors scrape tissue from the uterine lining for analysis—a procedure called dilation and curettage (D and C). At the same time, doctors usually view the interior of the uterus using a thin, flexible viewing tube inserted through the vagina and cervix into the uterus in a procedure called hysteroscopy. Alternatively, an ultrasound device may be inserted through the vagina into the uterus (called transvaginal ultrasonography) to evaluate abnormalities. However, a biopsy is still necessary to make the diagnosis.

If endometrial cancer is diagnosed, some or all of the following procedures may be done:

  • Blood tests

  • Kidney and liver function tests (using samples of blood or urine)

  • A chest x-ray

  • Electrocardiography

If results of the physical examination or other tests suggest that the cancer has spread beyond the uterus, computed tomography (CT) is done. Other procedures are sometimes required.

Staging of endometrial cancer

Staging is based on information obtained from these procedures and during surgery to remove the cancer.

Stages are based on how far the cancer has spread. Stages range from I (the earliest) to IV (advanced):

  • Stage I: The cancer occurs only in the upper part of the uterus, not in the lower part (cervix).

  • Stage II: The cancer has spread to the cervix.

  • Stage III: The cancer has spread to nearby tissues, the vagina, or lymph nodes.

  • Stage IV: The cancer has spread to the bladder and/or intestine or to distant organs.

Prognosis

Prognosis depends on the stage of the endometrial cancer.

The percentages of women who are alive 5 years after diagnosis and treatment (5-year survival rate) are

  • Stage I or II: 70 to 95% (most are cured)

  • Stage III or IV: 10 to 60%

Overall, 63% of women are cancer-free 5 years after treatment.

Generally, the prognosis is better if

  • Endometrial cancer has not spread beyond the uterus.

  • The cancer grows relatively slowly.

  • Women are younger when the cancer is detected.

Prevention

No measure can prevent endometrial cancer from developing. However, the risk of getting endometrial cancer can be decreased by minimizing or avoiding conditions and activities thought to increase the risk. For example, obesity and high blood pressure increase the risk of endometrial cancer. Thus, losing weight, exercising regularly, and eating a healthful diet may be helpful.

Treatment

  • Removal of the uterus, fallopian tubes, and ovaries

  • Removal of nearby lymph nodes

  • For more advanced cancer, radiation therapy with or without chemotherapy

Hysterectomy (surgical removal of the uterus) is the mainstay of treatment for women who have endometrial cancer. If the cancer has not spread beyond the uterus, removal of the uterus plus removal of the fallopian tubes and ovaries (salpingo-oophorectomy) almost always cures the cancer. Unless the cancer is very advanced, hysterectomy improves the prognosis. Nearby lymph nodes are usually removed at the same time. These tissues are examined by a pathologist to determine whether the cancer has spread and, if so, how far it has spread. With this information, doctors can determine whether additional treatment (chemotherapy, radiation therapy, or a progestin) is needed after surgery.

Doctors can remove the uterus, fallopian tubes, and ovaries using one of the following methods:

  • Making an incision in the abdomen (open surgery)

  • Using a thin, flexible viewing tube (laparoscope) inserted through a small incision just below the navel, then threading instruments through the laparoscope, sometimes with robotic assistance (laparoscopic surgery)

  • Removing the tissues through the vagina (vaginal surgery)

For very advanced cancer, treatment varies but usually involves a combination of surgery, radiation therapy, chemotherapy, and occasionally progestins (synthetic drugs similar to the hormone progesterone).

Radiation therapy may be given after surgery in case some undetected cancer cells remain. If the cancer has spread to the cervix or beyond the uterus, radiation therapy is usually recommended after surgery. In some cases (as when cancer has spread to the cervix, an ovary, or lymph nodes), surgery plus radiation therapy results in a better prognosis.

If the cancer has spread to distant organs or recurs, chemotherapy drugs (such as carboplatin, cisplatin, doxorubicin, and paclitaxel) may be used instead of or sometimes with radiation therapy. These drugs reduce the cancer’s size and control its spread in more than half of women treated. However, these drugs are toxic and have many side effects.

Sometimes progestins are used. These drugs are much less toxic than chemotherapy drugs.

For sarcoma of the uterus (a more aggressive form of endometrial cancer), treatment is hysterectomy plus removal of the fallopian tubes and ovaries (salpingo-oophorectomy). If surgery is not possible, radiation and/or chemotherapy is used.

If menopausal symptoms such as hot flashes and vaginal dryness become bothersome after the uterus is removed, hormones such as estrogen, a progestin, or both can taken to relieve them. This treatment is safe and does not increase the risk of developing cancer again.

Pregnancy and endometrial cancer

Treatment with radical hysterectomy, chemotherapy, and/or radiation therapy usually makes it impossible for women to become pregnant or to carry a pregnancy to term. However, advances in assisted reproductive techniques may enable women to have a child after these procedures. If being able to have children is important to them, women should talk to their doctor and get as much information as possible about risks of and requirements for these procedures, as well as the likelihood of becoming pregnant and having a child after such a procedure.

If endometrial cancer is in a very early stage, fertility preservation treatment can sometimes be used. Magnetic resonance imaging (MRI) is done to determine whether the tumor has spread, and a fertility specialist is consulted.

Fertility preservation treatments include

  • Use of a progestin (a synthetic drug similar to the hormone progesterone), which can shrink the tumor

  • Use of an intrauterine device (IUD) that releases levonorgestrel (a progestin)

  • Rarely, fertility-preserving (conservative) surgery

In fertility-preserving surgery, doctors remove only the tumor and the tissue around and under the tumor.

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