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Gestational trophoblastic disease

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Treatment of gestational trophoblastic disease

Treatment for gestational trophoblastic disease (GTD) is given by cancer specialists (oncologists). Some specialize in surgery, some in radiation therapy and others in chemotherapy (drugs). These doctors work with the woman with cancer to decide on a treatment plan.

Treatment plans are designed to meet the unique needs of each person with cancer. Treatment decisions for GTD are based on:

  • type of GTD
  • stage of GTD
  • level of risk
  • human chorionic gonadotropin (HCG) levels
  • the woman’s desire to preserve her fertility
  • whether the woman had previous treatment

Treatment options for gestational trophoblastic disease

Treatment for gestational trophoblastic tumours should be started as soon as possible after diagnosis.

Surgery

Surgery is one of the main treatments for GTD. Surgery may be used:

  • as the primary treatment for GTD
  • if GTD comes back after other treatments.

Dilation and curettage

Dilation and curettage (D&C) is a surgical procedure that dilates (opens) the cervix and then uses a vacuum-like device and a small, sharp instrument (curette) to remove tissue from the lining of the uterus. A woman may also be given a drug that causes the uterus to contract, which helps to push tissue from the uterus.

D&C is a treatment option for women diagnosed with complete or partial hydatidiform moles by human chorionic gonadotropin (HCG or b-HCG) testing or ultrasound. D&C will not be done if a gestational choriocarcinoma is suspected because this type of tumour bleeds very easily.

Women whose HCG levels do not return to normal after D&C or medical termination of a pregnancy (see below) will require further treatment. Women who are diagnosed with gestational choriocarcinoma or placental type trophoblastic tumour will also need further treatment.

Medical termination of pregnancy

Medical termination of pregnancy is a treatment option for women who are not eligible to have a D&C. Women who cannot have a D&C and who have their pregnancies terminated are at an increased risk of persistent trophoblastic disease.

Hysterectomy

Hysterectomy is the surgical removal of the uterus. Hysterectomy may be offered to women with malignant GTD that has not spread outside of the uterus and who no longer wish to have children. Hysterectomy may also be recommended to women with malignant GTD that does not respond to chemotherapy.

Hysterectomy is the primary treatment for women with placental site trophoblastic tumours because this type of cancer does not respond well to chemotherapy.

Surgery to remove metastases

Surgery may be done for GTD that has spread to distant sites in the body, such as the brain, intestines, kidney, liver, lungs and spleen. In the case of brain metastases, surgery may only be done if a tumour is close to the surface of the brain.

Potential side effects of surgery

Side effects of surgery for GTD will mainly depend on the:

  • type of surgery
  • woman’s overall health

Chemotherapy

Chemotherapy is the use of anti-cancer (cytotoxic) drugs to treat cancer. It is usually a systemic therapysystemic therapyTreatment that travels through the bloodstream to reach cells all over the body. that circulates throughout the body and destroys cancer cells, including those that may have broken away from the primary tumour.

Chemotherapy is a standard treatment for malignant GTD. It may be given:

  • as the main treatment
  • after surgery
  • with radiation therapy
  • if the cancer comes back (recurs) after treatment
  • if HCG levels do not return to normal after surgery

Single-agent chemotherapy is used for low-risk GTD (metastatic and non-metastatic) in women who wish to have children. The most common chemotherapy drugs include:

  • methotrexate (with or without folinic acid [leucovorin] rescue)
    • Radiation therapy may be used in combination with methotrexate intrathecal chemotherapy to treat GTD that has spread to the brain.
  • dactinomycin (Cosmegen, actinomycin-D)
  • etoposide (Vepesid)
  • ifosfamide (Ifex)
  • paclitaxel (Taxol)

Combination chemotherapy is used for high-risk GTD (metastatic or non-metastatic). The most common chemotherapy combinations include:

  • MAC – methotrexate, dactinomycin and chlorambucil (Leukeran)
  • EMA-CO – etoposide, methotrexate and dactinomycin, followed by cyclophosphamide (Cytoxan, Procytox) and vincristine (Oncovin)
  • EMA-CE – etoposide, methotrexate and dactinomycin, followed by cisplatin (Platinol AQ) and etoposide
  • EMA – etoposide, methotrexate and dactinomycin
  • VBP - vinblastine (Velbe), bleomycin (Blenoxane) and cisplatin
  • BEP - bleomycin, etoposide and cisplatin
  • CHAMOCA - methotrexate, dactinomycin, cyclophosphamide, doxorubicin (Adriamycin), melphalan (Alkeran, L-PAM), hydroxyurea (Hydrea) and vincristine
  • CHAMOMA - methotrexate, folinic acid, hydroxyurea, dactinomycin, vincristine, melphalan and doxorubicin
  • etoposide, cisplatin and dexamethasone (Decadron, Dexasone)

The time between chemotherapy cycles is usually 14–21 days. It is rarely longer than 21 days. HCG levels are closely monitored. Once the HCG level returns to normal, chemotherapy is usually given for 1-3 more cycles.

Potential side effects of chemotherapy

Side effects of chemotherapy will depend mainly on:

  • the type of drug(s)
  • the dose
  • how the drug is given
  • the woman’s overall health

Radiation therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. External beam radiation therapy is the type of radiation therapy most often used to treat GTD. Radiation therapy may be used in combination with methotrexate intrathecal chemotherapy to treat GTD that has spread to the brain.

Potential side effects of radiation therapy

Side effects of radiation therapy to the brain will depend mainly on the:

  • size of the area being treated
  • total dose
  • treatment schedule

Supportive therapy

Women with high-risk GTD may need to be treated with supportive therapy. Supportive therapy helps to reduce some of the side effects associated with certain drugs so doctors can give the appropriate dose of chemotherapy.

Supportive therapy may include:

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Treatment by type of GTD and level of risk

Treatment of GTD depends on the type and level of risk. Since hydatidiform moles are a benign form of GTD, they are treated differently. Placental site trophoblastic tumours are malignant forms of GTD and they are also treated differently (see below).

Hydatidiform moles

Treatment options for hydatidiform moles may include:

  • dilation and curettage (D&C)
    • D&C is used for women who still wish to have children.
    • Some women may need a second D&C if some of the molar tissue remains after the first D&C.
  • hysterectomy
    • This surgery may be offered to women who no longer wish to have children.
  • prophylacticprophylacticReferring to or having to do with actions that are intended to prevent or avoid disease. chemotherapy
    • This treatment may be offered to some women following D&C or hysterectomy.
    • It may be given to women believed to have a hydatidiform mole that has a high risk of becoming malignant and spreading.
    • It may also be offered to women who are unlikely to participate in follow-up HCG testing or women who live in remote areas and have limited access to HCG testing.

Low-risk gestational trophoblastic disease

Low-risk GTD includes invasive moles and gestational choriocarcinoma that is most likely to respond to treatment.

Low-risk GTD may be treated with:

  • chemotherapy
    • methotrexate
    • methotrexate (with folinic acid rescue)
    • dactinomycin
    • etoposide
  • hysterectomy
    • may be offered to women who no longer wish to have children

High-risk gestational trophoblastic disease

High-risk GTD includes invasive moles and gestational choriocarcinoma that may be less responsive to treatment.

High-risk GTD may be treated with:

  • chemotherapy
    • EMA-CO – etoposide, methotrexate and dactinomycin, followed by cyclophosphamide and vincristine
    • MAC – methotrexate, dactinomycin and chlorambucil
    • MFA – methotrexate, folinic acid and dactinomycin
    • EMA – etoposide, methotrexate and dactinomycin
    • CHAMOCA - methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine
    • CHAMOMA - methotrexate, folinic acid, hydroxyurea, dactinomycin, vincristine, melphalan and doxorubicin
  • surgery
    • hysterectomy
    • surgery to remove metastases

Recurrent and resistant gestational trophoblastic disease

Treatment for recurrent GTD depends on where the tumour has recurred and what type of treatment a woman previously had for the disease. GTD that recurs or does not respond to drugs used in earlier treatments may be treated with:

  • chemotherapy
    • dactinomycin, with or without etoposide
    • paclitaxel
    • EMA-CE – etoposide, methotrexate and dactinomycin, followed by cisplatin and etoposide
    • MAC – methotrexate, dactinomycin and chlorambucil
    • EMA-CO – etoposide, methotrexate and dactinomycin, followed by cyclophosphamide and vincristine
    • VBP - vinblastine, bleomycin and cisplatin
    • BEP - bleomycin, etoposide, cisplatin
    • TP-TE - paclitaxel and cisplatin, followed by paclitaxel and etoposide
    • APE – dactinomycin, cisplatin and etoposide
    • MBE – methotrexate, bleomycin and etoposide
  • surgery
    • hysterectomy
    • surgery to remove metastases

Placental site trophoblastic tumours

Placental site trophoblastic tumours are a very rare type of GTD. They usually don’t spread beyond the muscle wall of the uterus (myometrium). This type of tumour is very resistant to chemotherapy, so it is often treated with a hysterectomy. Lymph nodes may also be removed at the time of surgery.

In the rare situation where placental site trophoblastic tumours spread to other parts of the body (metastasize), chemotherapy may be offered. There is little research on the best type of chemotherapy for metastatic placental site trophoblastic tumours. The types of chemotherapy given may include:

  • EMA-CO – etoposide, methotrexate and dactinomycin, followed by cyclophosphamide and vincristine
  • EP-EMA – etoposide and cisplatin, followed by etoposide, methotrexate and dactinomycin
  • MAE – methotrexate with folinic acid rescue, dactinomycin and etoposide
  • TP-TE - paclitaxel and cisplatin, followed by paclitaxel and etoposide

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Clinical trials

Clinical trials investigate new and better ways to prevent, detect and treat cancer. There are a few clinical trials in Canada that are open to women with GTD. For more information, go to clinical trials.

See a list of questions to ask your doctor about treatment.

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Follow-up after treatment for gestational trophoblastic disease

GTD behaves differently in each woman, and a standard follow-up schedule would not work for everyone. Women with GTD should talk to their doctor about a follow-up plan that suits their individual situation. Follow-up care is often shared among the cancer specialists (oncologists), surgeon, gynecologist and the family doctor.

After treatment has ended, new symptoms and symptoms that don’t go away should be reported to the doctor without waiting for the next scheduled appointment. These may include:

  • irregular vaginal bleeding
  • coughing up blood
  • shortness of breath
  • chest pain
  • any new lump or swelling
  • seizure
  • headaches
  • gradual loss of the ability to move a body part (paralysis)

The chance of GTD recurring is greatest within the first year, so close follow-up is needed during this time.

Schedule

Follow-up after GTD treatment varies. Follow-up visits are usually scheduled:

  • every 3–6 months in the first 2 years
    • HCG testing is done more often (see below).

Procedures

During a follow-up visit, the doctor usually asks questions about the side effects of treatment and how the woman is coping. The doctor may do a complete physical examination, including:

  • pelvic examination
  • feeling the lymph nodes (to check for spread in women diagnosed with placental site trophoblastic tumours)

Tests may be ordered as part of follow-up or if the doctor suspects the cancer has come back (has recurred).

Laboratory tests

HCG testing

  • HCG is a very sensitive test for diagnosing the recurrence of GTD. Changes in the level of HCG are usually the first sign that GTD has recurred. This test is also done regularly as part of follow-up to monitor the response to treatment.
  • HCG levels are tested every week until there has been no HCG in the blood for 3-4 weeks in a row.
    • hydatidiform mole – Once there has been no HCG detected in the blood for 3-4 weeks in a row, HCG levels are then tested each month for 6 months, and then every 2 months for the next 6 months to make sure that there is no HCG in the blood. Women are usually advised to use contraception and not to become pregnant again until the HCG values have been normal for 6 months.
    • malignant GTD – HCG levels are tested each month for 1–2 years after chemotherapy is completed to make sure there is no HCG in the blood. Women are advised to use contraception and not to become pregnant during active follow-up (1–2 years).
  • A rising HCG level may mean that the gestational trophoblastic tumour has recurred.

Human placental lactogen (hPL) testing

  • hPL testing is often done to check for recurrence in women with placental site trophoblastic tumours.

Urine tests

  • Urine tests may be done to check HCG levels in the urine.

Imaging tests

Imaging tests are rarely ordered for follow-up because HCG is a simple way to tell if treatment is working or diagnose a recurrence of GTD. A woman will usually have an imaging test if the HCG level rises or does not return to normal. Imaging tests that may be done include:

Other tests

If the doctor suspects that a woman has had a recurrence of GTD, other tests may be ordered. These may include:

  • lumbar puncture
  • biopsy

If a recurrence is found during follow-up, the oncology team will assess the woman with cancer to determine the best treatment options.

See a list of questions to ask your doctor about follow-up after treatment.

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