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How We Treat GTD

  • Ross Berkowitz, MD

    After the diagnosis of complete or partial hydatidiform mole is made or suspected, the uterine contents are removed by suctioning (called dilation and evacuation, D&E).

    Hysterectomy may be advisable in older patients who have completed childbearing to reduce the risk of malignancy. After the uterus is emptied, testing for human chorionic gonadotropin (hCG, a hormone normally produced after conception) should be performed every week in order to determine if the molar pregnancy is malignant. If the molar pregnancy is benign, the hormone level will become undetectable in 8-12 weeks. Hormone testing should be continued until three weekly negative levels are obtained, then followed by monthly tests for six months, after which pregnancy is permitted. During the six-month follow-up, it is important to avoid pregnancy. The use of oral contraceptives is safe.

  • A rise in the hormone level indicates that the molar pregnancy is malignant GTD (also called gestational trophoblastic neoplasia, GTN). More tests will be done to find out if the cancer has spread from the uterus to other parts of the body (called staging). Even if GTD has spread to other parts of the body, it is still highly curable. The stages of malignant GTD are:

    • Stage I: The cancer has not spread from the uterus
    • Stage II: The cancer has spread from the uterus to other structures in the pelvis
    • Stage III: The cancer has spread to the lungs
    • Stage IV: The cancer has spread to other organs

    The treatment of malignant GTD depends on the stage and number of risk factors, which determine the type of drugs that will most likely cure the disease. The factors that are characteristic of women who are likely to be cured by one or more single chemotherapy drugs (called low-risk malignant GTD) include:

    • The last pregnancy was less than four months ago
    • The level of hCG in the blood is low
    • The cancer has not spread to the liver, brain, and/or other distant organs
    • The patient has not received chemotherapy treatments earlier

    The risk factors for women who develop malignant GTD who are NOT likely to be cured by one or more single chemotherapy drugs and who require treatments containing multiple agents (called high-risk malignant GTD) are:

    • The last pregnancy was more than four months ago
    • The level of hCG in the blood is high
    • The cancer has spread to the liver, brain, and/or other distant organs
    • The patient received chemotherapy earlier and the cancer did not go away
    • The tumor began after completion of a normal pregnancy

    Follow-up care

    Hormone follow-up by measuring the level of human chorionic gonadotropin (hCG) in blood continues until the hormone level is normal for three weeks, and should continue monthly for 12 months (24 months for patients with Stage IV disease). During that time, patients should avoid pregnancy, since women who conceive within 12 months of completing chemotherapy have an increased risk of miscarriage — particularly if they have received multiple chemotherapeutic agents. If pregnancy occurs before follow-up is complete, tumor relapse may be difficult to detect, and diagnosis of relapse may be delayed.

    The chemotherapy used for the treatment of malignant GTD is generally well tolerated without long-term side effects, with one exception — the use of multi-agent chemotherapy is associated with an earlier menopause.

    Recurrent disease

    GTD (also called gestational trophoblastic neoplasia, or GTN) is a highly curable disease. Women with hydatidiform mole have an excellent prognosis, and women with malignant GTD usually have a very good prognosis. Choriocarcinoma, for example, is an uncommon — yet almost always curable — cancer. Although choriocarcinoma is a highly malignant tumor and life-threatening disease, it is very sensitive to chemotherapy. About 85-90 percent of women with low-risk malignant GTD are cured by the initial chemotherapy, and the remaining are cured by the use of stronger combinations of drugs, or by surgery.

    Similarly, 85-90 percent of women who develop high-risk malignant GTD are cured by chemotherapy used together with selective surgery and radiation.

    Approximately 10-15 percent of women with high-risk malignant GTD will develop drug resistance after prolonged chemotherapy. This group consists of patients with stage IV disease that involves distant organs such as the brain, liver, and bowel. Specially-designed chemotherapy treatments using drugs that have been shown to be effective against other cancers are being employed to assist in treating many of these women.

    Three kinds of treatment can be used for malignant GTD:

    • Chemotherapy (using drugs to eliminate the cancer)
    • Radiation therapy (uses high energy x-rays to eliminate cancer cells and shrink tumors)
    • Surgery (removing the cancer)

    Chemotherapy is the main treatment for malignant GTD and is generally highly effective. Chemotherapy uses drugs to eliminate cancer cells. It may be taken by pill, or by a needle in vein or muscle. It is called systemic treatment because the drugs enter the bloodstream, travel through the body, and can kill cancer cells outside the uterus. Chemotherapy may be given before or after surgery or alone. Patients can preserve fertility and still be cured with chemotherapy even in the presence of widespread disease.

    Radiation may infrequently be used in certain cases to treat cancer that has spread to other parts of the body, particularly the brain. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials that produce radiation (radioisotopes) inserted through thin plastic tubes into the area where the cancer cells are found (internal radiation).

    The most common surgery for malignant GTD is hysterectomy, an operation to take out the uterus. Surgery may also be used to remove cancer involving the lungs and other organs that have not gone away with drug therapy.

    Placental-site trophoblastic tumors and epithelioid trophoblastic tumors, unlike choriocarcinoma, are not sensitive to chemotherapy. Since in most cases the tumor is localized to the uterus, hysterectomy provides the best outcome. When the disease spreads outside the uterus, high-dose chemotherapy is used with some success.

    Becoming pregnant again

    After completing hormone follow-up for hydatidiform mole, women may try for pregnancy whenever they wish. The risk of another molar pregnancy is low. More than 98 percent of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk for complications. However, since patients with hydatidiform mole are at some increased risk of another molar pregnancy, it is advisable for them to undergo ultrasound examinations at 10 weeks of gestation to determine if the pregnancy is progressing normally.

    Most women who require treatment for malignant GTD can become pregnant again and have normal pregnancies. After chemotherapy is completed, women should postpone pregnancy for 12 months (24 months for women with stage IV disease) while they are being followed with hormone testing to make sure the tumor does not recur. There does not appear to be an increased rate of congenital malformation irrespective of the chemotherapy used. Following GTD, the expectation of normal pregnancies is about comparable to the general population.