Ovarian Cancer

• Ovarian cancer may not cause symptoms until it is large or has spread.
• If doctors suspect ovarian cancer, ultrasonography, magnetic resonance imaging, or computed tomography is done.
• Usually, both ovaries, both fallopian tubes, and the uterus are removed.
• Chemotherapy is often needed after surgery.

Cancer of the ovaries (ovarian carcinoma) develops most often in women aged 50 to 70. This cancer eventually develops in about 1 of 70 women. In the United States, it is the second most common gynecologic cancer. However, more women die of ovarian cancer than of any other gynecologic cancer. It is the fifth most common cause of cancer deaths in women.

Factors that increase the risk of ovarian cancer include the following:

• Being older (the most important)
• Not having any children
• Having a first child late in life
• Starting menstruating early
• Having menopause late
• Having had or having a family member who had cancer of the uterus, breast, or large intestine (colon)

The risk of ovarian cancer is higher in developed countries because the diet tends to be high in fat. Use of oral contraceptives significantly decreases risk.

About 5 to 10% of cases are related to the BRCA gene, which is also involved in some breast cancers. In these cases, ovarian and breast cancer tends to run in families. This abnormal gene is most common among Ashkenazi Jewish women.

There are many types of ovarian cancer. They develop from the many different types of cells in the ovaries. Cancers that start on the surface of the ovaries (epithelial carcinomas) account for at least 80%. Most other ovarian cancers start from the cells that produce eggs (called germ cell tumors) or in connective tissue (called stromal cell tumors). Germ cell tumors are much more common among women younger than 30. Sometimes cancers from other parts of the body spread to the ovaries.

Ovarian cancer can spread directly to the surrounding area and through the lymphatic system to other parts of the pelvis and abdomen. It can also spread through the bloodstream, eventually appearing in distant parts of the body, mainly the liver and lungs.

Symptoms

Ovarian cancer causes the affected ovary to enlarge. In young women, enlargement of an ovary is likely to be caused by a noncancerous fluid-filled sac (cyst). However, after menopause, an enlarged ovary can be a sign of ovarian cancer.

Many women have no symptoms until the cancer is advanced. The first symptom may be vague discomfort in the lower abdomen, similar to indigestion. Other symptoms may include bloating, loss of appetite (because the stomach is compressed), gas pains, and backache. Ovarian cancer rarely causes vaginal bleeding.

Eventually, the abdomen may swell because the ovary enlarges or fluid accumulates in the abdomen. At this stage, pain in the pelvic area, anemia, and weight loss are common. Rarely, germ cell or stromal cell tumors produce estrogens, which can cause tissue in the uterine lining to grow excessively and breasts to enlarge. Or these tumors may produce male hormones (androgens), which can cause body hair to grow excessively, or hormones that resemble thyroid hormones, which can cause hyperthyroidism.

Diagnosis

Diagnosing ovarian cancer in its early stages is difficult because symptoms usually do not appear until the cancer is quite large or has spread beyond the ovaries and because many less serious disorders cause similar symptoms.

If doctors detect an enlarged ovary during a physical examination, ultrasonography is done first. Sometimes computed tomography (CT) or magnetic resonance imaging (MRI) is used to help distinguish an ovarian cyst from a cancerous mass. If advanced cancer is suspected, CT or MRI is usually done before surgery to determine extent of the cancer.

If cancer seems unlikely, doctors reexamine the woman periodically.

If doctors suspect cancer or test results are unclear, the ovaries are examined using a thin, flexible viewing tube (laparoscope) inserted through a small incision just below the navel. Also, tissue samples are removed using instruments threaded through the laparoscope and examined (biopsied). In addition, blood tests are usually done to measure levels of substances that may indicate the presence of cancer (tumor markers), such as cancer antigen 125 (CA 125). Abnormal marker levels alone do not confirm the diagnosis of cancer, but when combined with other information, they can help confirm it.

If fluid has accumulated in the abdomen, it can be drawn out (aspirated) through a needle and tested to determine whether cancer cells are present.

If doctors suspect advanced cancer or cancer is confirmed, they make an incision in the abdomen to obtain a tissue sample. At the same time, they remove as much of the cancer as possible and determine how far the cancer has spread (its stage).

Prognosis

The prognosis is based on the stage (see Cancers of the Female Reproductive System: Staging Cancers of the Female Reproductive System*). The percentages of women who are alive 5 years after diagnosis and treatment are

• Stage I: 70 to 100%
• Stage II: 50 to 70%
• Stage III: 20 to 50%
• Stage IV: 10 to 20%

The prognosis is worse when the cancer is more aggressive or when surgery cannot remove all visibly abnormal tissue. Cancer recurs in 70% of women who have had stage III or IV cancer.

Prevention

Some experts believe that if ovarian or breast cancer runs in the family, women should be tested for genetic abnormalities. If first- or second-degree relatives have such cancers, particularly among Ashkenazi Jewish families, women should discuss genetic testing for BRCA abnormalities with their doctors. Women with certain BRCA gene mutations may be offered the option of having both ovaries and tubes removed after they no longer wish to bear children, even when no cancer is present. This approach eliminates the risk of ovarian cancer and reduces the risk of breast cancer. These women should be evaluated by a gynecologist who specializes in cancer (gynecologic oncologist). More information is available from the National Cancer Institute Cancer Information Service (1-800-4-CANCER) and the Women's Cancer Network (WCN) web site (www.wcn.org).

Treatment

The extent of surgery depends on the type of ovarian cancer and the stage. For most cancers, the ovaries, fallopian tubes, and uterus are removed. When cancer has spread beyond the ovary, nearby lymph nodes and surrounding structures that the cancer typically spreads to are also removed. If a woman has stage I cancer that affects only one ovary and she wishes to become pregnant, doctors may remove only the affected ovary and fallopian tube. For more advanced cancers that have spread to other parts of the body, removing as much of the cancer as possible prolongs survival.

After surgery, most women with stage I epithelial carcinomas usually require no further treatment. For other stage I cancers or for more advanced cancers, chemotherapy may be used to destroy any small areas of cancer that may remain. Typically, chemotherapy consists of paclitaxel Some Trade Names
ABRAXANETAXOL
combined with carboplatin Some Trade Names
PARAPLATIN
, given 6 times. Most women with germ cell tumors can be cured with removal of the one affected ovary and fallopian tube plus combination chemotherapy, usually with bleomycin Some Trade Names
BLENOXANE
, cisplatin Some Trade Names
PLATINOL
, and etoposide Some Trade Names
VEPESID
. Radiation therapy is rarely used.

Advanced ovarian cancer usually recurs. So after chemotherapy, doctors typically measure levels of cancer markers. If the cancer recurs, chemotherapy (using drugs such as carboplatin Some Trade Names
PARAPLATIN
, doxorubicin Some Trade Names
DOXIL
, etoposide Some Trade Names
VEPESID
, gemcitabine Some Trade Names
GEMZAR
, paclitaxel Some Trade Names
ABRAXANETAXOL
, or topotecan Some Trade Names
HYCAMTIN
) is given.

What Is an Ovarian Cyst? An ovarian cyst is a fluid-filled sac in or on an ovary. Such cysts are relatively common. Most are noncancerous and disappear on their own. Cancerous cysts are more likely to occur in women older than 40. Most noncancerous ovarian cysts do not cause symptoms. However, some cause pressure, aching, or a feeling of heaviness in the abdomen. Pain may be felt during sexual intercourse. If a cyst ruptures or becomes twisted, severe stabbing pain is felt in the abdomen. The pain may be accompanied by nausea and fever. Some cysts produce hormones that affect menstrual periods. As a result, periods may be irregular or heavier than normal. In postmenopausal women, such cysts may cause vaginal bleeding. Women who have any of these symptoms should see a doctor. Doctors may find a cyst during a routine pelvic examination or occasionally suspect it based on symptoms. A pregnancy test is done to exclude that possibility. An ultrasound device may be inserted through the vagina into the uterus (transvaginal ultrasonography) to confirm the diagnosis. If the cyst appears to be noncancerous, a woman may be asked to return periodically for pelvic examinations as long as the cyst remains. If the cyst could be cancerous, computed tomography (CT) or magnetic resonance imaging (MRI) may be done. If cancer still seems possible, the ovaries may be examined through a laparoscope, inserted through a small incision just below the navel. Blood tests can help confirm or rule out cancer. For noncancerous cysts, no treatment is necessary. But if a cyst is larger than about 2 inches (5 centimeters) and persists, it may need to be removed. If cancer cannot be ruled out, the ovary is removed. Cancerous cysts plus the affected ovary and fallopian tube are removed. Surgery may be done through a laparoscope (with only a small incision) or a larger incision in the abdomen.

Hydatidiform Mole

A hydatidiform mole is growth of an abnormal fertilized egg or an overgrowth of tissue from the placenta.

• Women appear to be pregnant, but the uterus enlarges much more rapidly than in a normal pregnancy.
• Most women have severe nausea and vomiting, vaginal bleeding, and very high blood pressure.
• Ultrasonography, blood tests to measure human chorionic gonadotropin (which is produced early during pregnancy) and a biopsy are done.
• Moles are removed using dilation and curettage with suction.
• If the disorder persists, chemotherapy is needed.

Most often, a hydatidiform mole is an abnormal fertilized egg that develops into a hydatidiform mole rather than a fetus (a condition called molar pregnancy). However, a hydatidiform mole can develop from cells that remain in the uterus after a miscarriage or a full-term pregnancy. Rarely, a hydatidiform mole develops when there is a living fetus. In such cases, the fetus typically dies, and a miscarriage often occurs.

Hydatidiform moles are most common among women under 17 or over 35. In the United States, they occur in about 1 in 2000 pregnancies in the United States. For unknown reasons, moles are almost 10 times more common in Asian countries.

About 80% of hydatidiform moles are not cancerous. About 15 to 20% invade the surrounding tissue and tend to persist. About 2 to 3% become cancerous and spread throughout the body; they are then called choriocarcinomas. Choriocarcinomas can spread quickly through the lymphatic vessels or bloodstream. Hydatidiform moles and choriocarcinomas are types of gestational trophoblastic disease.

Did You Know... An abnormal fertilized egg or placental tissue can overgrow, causing symptoms similar to those of pregnancy but with a more rapid enlargement of the abdomen.

Symptoms

Women who have a hydatidiform mole feel as if they are pregnant. But because hydatidiform moles grow much faster than a fetus, the abdomen becomes larger much faster than it does in a normal pregnancy. Severe nausea and vomiting are common, and vaginal bleeding may occur. As parts of the mole deteriorate, small amounts of tissue, which resemble a bunch of grapes, may pass through the vagina. These symptoms indicate the need for prompt evaluation by a doctor.

Hydatidiform moles can cause serious complications, including infections and very high blood pressure with increased protein in the urine (preeclampsia or eclampsia—see Pregnancy Complications: Preeclampsia).

If choriocarcinoma develops, women may have other symptoms, caused by spread (metastasis) to other parts of the body.

Diagnosis

Often, doctors can diagnose a hydatidiform mole shortly after conception. The pregnancy test is positive, but no fetal movement and no fetal heartbeat are detected, and the uterus is much larger than expected.

Ultrasonography is done to be sure that the growth is a hydatidiform mole and not a fetus or amniotic sac (which contains the fetus and fluid around it). Blood tests to measure the level of human chorionic gonadotropin (hCG—a hormone normally produced early in pregnancy) are done. If a hydatidiform mole is present, the level is usually very high because the mole produces a large amount of this hormone. A sample of tissue is removed or obtained when it is passed, then examined under a microscope (biopsy) to confirm the diagnosis.

Prognosis

The cure rate for a hydatidiform mole is virtually 100% if the mole has not spread. The cure rate is 60 to 80% for choriocarcinoma that has spread widely. Most women can have children afterwards and do not have a higher risk of having complications, a miscarriage, or children with birth defects.

About 1% of women who have had a hydatidiform mole have another one. So if women have had a hydatidiform mole, ultrasonography is done early in subsequent pregnancies.

Treatment

A hydatidiform mole is completely removed, usually by dilation and curettage (D and C) with suction (see Symptoms and Diagnosis of Gynecologic Disorders: Dilation and Curettage). Only rarely is removal of the uterus (hysterectomy) necessary.

A chest x-ray is done to see whether the mole has become cancerous (that is, a choriocarcinoma) and spread to the lungs. After surgery, the level of human chorionic gonadotropin in the blood is measured to determine whether the hydatidiform mole was completely removed. When removal is complete, the level returns to normal, usually within 10 weeks, and remains normal. If the level does not return to normal (called persistent disease), computed tomography (CT) of the brain, chest, abdomen, and pelvis is done to determine whether choriocarcinoma has developed and spread.

Hydatidiform moles do not require chemotherapy, but persistent disease does. Usually, only one drug ( methotrexate Some Trade Names
TREXALL
or dactinomycin Some Trade Names
COSMEGEN
) is needed. Sometimes both drugs or another combination of chemotherapy drugs is needed.

Women who have had a hydatidiform mole removed are advised not to become pregnant for 1 year. Oral contraceptives are frequently recommended, but other effective contraceptive methods can be used.

Fallopian Tube Cancer

Fallopian tube cancer develops in the tubes that lead from the ovaries to the uterus.

• Most cancers that affect the fallopian tubes have spread from other parts of the body.
• At first, women may have vague symptoms, such as abdominal discomfort or bloating, or no symptoms.
• Ultrasonography or computed tomography is done to check for abnormalities.
• Usually, the uterus, ovaries, and fallopian tubes are removed, followed by chemotherapy.

In the United States, fewer than 1% of gynecologic cancers are fallopian tube cancers. Most often, cancer that affects the fallopian tubes has spread from the ovaries rather than started in the fallopian tubes. Cancer that starts in the fallopian tubes usually affects women aged 50 to 60. It is more likely to develop in women who have had the following:

• Long-term inflammation of the fallopian tubes (chronic salpingitis)
• Disorders that cause inflammation in other parts of the body, such as tuberculosis
• Infertility

More than 95% of fallopian tube cancers are adenocarcinomas, which develop from gland cells. A few are sarcomas, which develop from connective tissue. Fallopian tube cancer spreads in much the same way as ovarian cancer: usually directly to the surrounding area or through the lymphatic system, eventually appearing in distant parts of the body.

Symptoms

Symptoms include vague abdominal discomfort, bloating, and pain in the pelvic area or abdomen. Some women have a watery or blood-tinged discharge from the vagina. When cancer is advanced, the abdominal cavity may fill with fluid (a condition called ascites), and women may feel a large mass in the pelvis.

Diagnosis

Fallopian tube cancer is seldom diagnosed early. Occasionally, it is diagnosed early when a mass or other abnormality is detected during a routine pelvic examination or an imaging test done for another reason. Usually, the cancer is not diagnosed until it is advanced, when it is obvious because a large mass or severe ascites is present.

If cancer is suspected, computed tomography (CT) is usually done. If the results suggest cancer, surgery is done to confirm the diagnosis, determine the extent of spread, and remove as much of the cancer as possible.

Prognosis and Treatment

The prognosis is similar to that for women who have ovarian cancer.

Treatment almost always consists of removal of the uterus (hysterectomy) and removal of the ovaries and fallopian tubes (salpingo-oophorectomy), adjacent lymph nodes, and surrounding tissues. Chemotherapy (as for ovarian cancer) is usually necessary after surgery. The most commonly used chemotherapy drugs are carboplatin Some Trade Names
PARAPLATIN
and paclitaxel Some Trade Names
ABRAXANETAXOL
.

For some cancers, radiation therapy is useful. For cancer that has spread to other parts of the body, removing as much of the cancer as possible improves the prognosis.