Gestational Trophoblastic Disease Treatment- Cancer/Oncology

Gestational Trophoblastic Disease Treatment (PDQ®)–Patient Version was originally published by the National Cancer Institute.

KEY POINTS

• Gestational trophoblastic disease (GTD) is a group of rare diseases in which abnormal trophoblast cells grow inside the uterus after conception.
• Hydatidiform mole (HM) is the most common type of GTD.
• Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease (GTD) that is almost always malignant.
  • Invasive moles
  • Choriocarcinomas
  • Placental-site trophoblastic tumors
  • Epithelioid trophoblastic tumors
• Age and a previous molar pregnancy affect the risk of GTD.
• Signs of GTD include abnormal vaginal bleeding and a uterus that is larger than normal.
• Tests that examine the uterus are used to detect (find) and diagnose gestational trophoblastic disease.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Gestational trophoblastic disease (GTD) is a group of rare diseases in which abnormal trophoblast cells grow inside the uterus after conception.

In gestational trophoblastic disease (GTD), a tumor develops inside the uterus from tissue that forms after conception (the joining of sperm and egg). This tissue is made of trophoblast cells and normally surrounds the fertilized egg in the uterus. Trophoblast cells help connect the fertilized egg to the wall of the uterus and form part of the placenta (the organ that passes nutrients from the mother to the fetus).

Sometimes there is a problem with the fertilized egg and trophoblast cells. Instead of a healthy fetus developing, a tumor form. Until there are signs or symptoms of the tumor, the pregnancy will seem like a normal pregnancy.

Most GTD is benign (not cancer) and does not spread, but some types become malignant (cancer) and spread to nearby tissues or distant parts of the body.

Gestational trophoblastic disease (GTD) is a general term that includes different types of disease:

• Hydatidiform Moles (HM)
  • Complete HM.
  • Partial HM.
• Gestational Trophoblastic Neoplasia (GTN)
  • Invasive moles.
  • Choriocarcinomas.
  • Placental-site trophoblastic tumors (PSTT; very rare).
  • Epithelioid trophoblastic tumors (ETT; even more rare).

Hydatidiform mole (HM) is the most common type of GTD.

HMs are slow-growing tumors that look like sacs of fluid. An HM is also called a molar pregnancy. The cause of hydatidiform moles is not known.

HMs may be complete or partial:

• A complete HM forms when sperm fertilizes an egg that does not contain the mother’s DNA. The egg has DNA from the father and the cells that were meant to become the placenta are abnormal.
• A partial HM forms when sperm fertilizes a normal egg and there are two sets of DNA from the father in the fertilized egg. Only part of the fetus forms and the cells that were meant to become the placenta are abnormal.

Most hydatidiform moles are benign, but they sometimes become cancer. Having one or more of the following risk factors increases the risk that a hydatidiform mole will become cancer:

• A pregnancy before 20 or after 35 years of age.
• A very high level of beta human chorionic gonadotropin (β-hCG), a hormone made by the body during pregnancy.
• A large tumor in the uterus.
• An ovarian cyst larger than 6 centimeters.
• High blood pressure during pregnancy.
• An overactive thyroid gland (extra thyroid hormone is made).
• Severe nausea and vomiting during pregnancy.
• Trophoblastic cells in the blood, which may block small blood vessels.
• Serious blood clotting problems caused by the HM.

Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease (GTD) that is almost always malignant.

Gestational trophoblastic neoplasia (GTN) includes the following:

Invasive moles

Invasive moles are made up of trophoblast cells that grow into the muscle layer of the uterus. Invasive moles are more likely to grow and spread than a hydatidiform mole. Rarely, a complete or partial HM may become an invasive mole. Sometimes an invasive mole will disappear without treatment.

Choriocarcinomas

A choriocarcinoma is a malignant tumor that forms from trophoblast cells and spreads to the muscle layer of the uterus and nearby blood vessels. It may also spread to other parts of the body, such as the brain, lungs, liver, kidney, spleen, intestines, pelvis, or vagina. A choriocarcinoma is more likely to form in women who have had any of the following:

• Molar pregnancy, especially with a complete hydatidiform mole.
• Normal pregnancy.
• Tubal pregnancy (the fertilized egg implants in the fallopian tube rather than the uterus).
• Miscarriage.

Placental-site trophoblastic tumors

A placental-site trophoblastic tumor (PSTT) is a rare type of gestational trophoblastic neoplasia that forms where the placenta attaches to the uterus. The tumor forms from trophoblast cells and spreads into the muscle of the uterus and into blood vessels. It may also spread to the lungs, pelvis, or lymph nodes. A PSTT grows very slowly and signs or symptoms may appear months or years after a normal pregnancy.

Epithelioid trophoblastic tumors

An epithelioid trophoblastic tumor (ETT) is a very rare type of gestational trophoblastic neoplasia that may be benign or malignant. When the tumor is malignant, it may spread to the lungs.

Age and a previous molar pregnancy affect the risk of GTD.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk to your doctor if you think you may be at risk. Risk factors for GTD include the following:

• Being pregnant when you are younger than 20 or older than 35 years of age.
• Having a personal history of hydatidiform mole.

Signs of GTD include abnormal vaginal bleeding and a uterus that is larger than normal.

These and other signs and symptoms may be caused by gestational trophoblastic disease or by other conditions. Check with your doctor if you have any of the following:

• Vaginal bleeding not related to menstruation.
• A uterus that is larger than expected during pregnancy.
• Pain or pressure in the pelvis.
• Severe nausea and vomiting during pregnancy.
• High blood pressure with headache and swelling of feet and hands early in the pregnancy.
• Vaginal bleeding that continues for longer than normal after delivery.
• Fatigue, shortness of breath, dizziness, and a fast or irregular heartbeat caused by anemia.

GTD sometimes causes an overactive thyroid. Signs and symptoms of an overactive thyroid include the following:

• Fast or irregular heartbeat.
• Shakiness.
• Sweating.
• Frequent bowel movements.
• Trouble sleeping.
• Feeling anxious or irritable.
• Weight loss.

Tests that examine the uterus are used to detect (find) and diagnose gestational trophoblastic disease.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. A speculum is inserted into the vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test of the cervix is usually done. The doctor or nurse also inserts one or two lubricated, gloved fingers of one hand into the vagina and places the other hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. The doctor or nurse also inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas.

• Ultrasound exam of the pelvis: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs in the pelvis and make echoes. The echoes form a picture of body tissues called a sonogram. Sometimes a transvaginal ultrasound (TVUS) will be done. For TVUS, an ultrasound transducer (probe) is inserted into the vagina to make the sonogram.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease. Blood is also tested to check the liver, kidney, and bone marrow.
• Serum tumor marker test: A procedure in which a sample of blood is checked to measure the amounts of certain substances made by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the body. These are called tumor markers. For GTD, the blood is checked for the level of beta human chorionic gonadotropin (β-hCG), a hormone that is made by the body during pregnancy. β-hCG in the blood of a woman who is not pregnant may be a sign of GTD.
• Urinalysis : A test to check the color of urine and its contents, such as sugar, protein, blood, bacteria, and the level of β-hCG.

Certain factors affect prognosis (chance of recovery) and treatment options.

Gestational trophoblastic disease usually can be cured. Treatment and prognosis depend on the following:

• The type of GTD.
• Whether the tumor has spread to the uterus, lymph nodes, or distant parts of the body.
• The number of tumors and where they are in the body.
• The size of the largest tumor.
• The level of β-hCG in the blood.
• How soon the tumor was diagnosed after the pregnancy began.
• Whether GTD occurred after a molar pregnancy, miscarriage, or normal pregnancy.
• Previous treatment for gestational trophoblastic neoplasia.

Treatment options also depend on whether the woman wishes to become pregnant in the future.

Stages of Gestational Trophoblastic Tumors and Neoplasia

KEY POINTS

• After gestational trophoblastic neoplasia has been diagnosed, tests are done to find out if cancer has spread from where it started to other parts of the body.
• There are three ways that cancer spreads in the body.
• Cancer may spread from where it began to other parts of the body.
• There is no staging system for hydatidiform moles.
• The following stages are used for GTN:
  • Stage I
  • Stage II
  • Stage III
  • Stage IV
• The treatment of gestational trophoblastic neoplasia is based on the type of disease, stage, or risk group.

After gestational trophoblastic neoplasia has been diagnosed, tests are done to find out if cancer has spread from where it started to other parts of the body.

The process used to find out the extent or spread of cancer is called staging, The information gathered from the staging process helps determine the stage of disease. For GTN, stage is one of the factors used to plan treatment.

The following tests and procedures may be done to help find out the stage of the disease:

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body onto film, making pictures of areas inside the body.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as brain and spinal cord. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells, so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that the cancer has spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if choriocarcinoma spreads to the lung, the cancer cells in the lung are actually choriocarcinoma cells. The disease is metastatic choriocarcinoma, not lung cancer.

There is no staging system for hydatidiform moles.

Hydatidiform moles (HM) are found in the uterus only and do not spread to other parts of the body.

The following stages are used for GTN:

Stage I

In stage I, the tumor is in the uterus only.

Stage II

In stage II, cancer has spread outside of the uterus to the ovary, fallopian tube, vagina, and/or the ligaments that support the uterus.

Stage III

In stage III, cancer has spread to the lung.

Stage IV

In stage IV, cancer has spread to distant parts of the body other than the lungs.

The treatment of gestational trophoblastic neoplasia is based on the type of disease, stage, or risk group.

Invasive moles and choriocarcinomas are treated based on risk groups. The stage of the invasive mole or choriocarcinoma is one factor used to determine risk group. Other factors include the following:

• The age of the patient when the diagnosis is made.
• Whether the GTN occurred after a molar pregnancy, miscarriage, or normal pregnancy.
• How soon the tumor was diagnosed after the pregnancy began.
• The level of beta human chorionic gonadotropin (β-hCG) in the blood.
• The size of the largest tumor.
• Where the tumor has spread to and the number of tumors in the body.
• How many chemotherapy drugs the tumor has been treated with (for recurrent or resistant tumors)?

There are two risk groups for invasive moles and choriocarcinomas: low risk and high risk. Patients with low-risk disease usually receive less aggressive treatment than patients with high-risk disease.

Placental-site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) treatments depend on the stage of disease.

Recurrent and Resistant Gestational Trophoblastic Neoplasia

Recurrent gestational trophoblastic neoplasia (GTN) is cancer that has recurred (come back) after it has been treated. The cancer may come back in the uterus or in other parts of the body.

Gestational trophoblastic neoplasia that does not respond to treatment is called resistant GTN.

Treatment Option Overview

KEY POINTS

• There are different types of treatment for patients with gestational trophoblastic disease.
• Three types of standard treatment are used:
  • Surgery
  • Chemotherapy
  • Radiation therapy
• New types of treatment are being tested in clinical trials.
• Treatment for gestational trophoblastic disease may cause side effects.
• Patients may want to think about taking part in a clinical trial.
• Patients can enter clinical trials before, during, or after starting their cancer treatment.
• Follow-up tests may be needed.

There are different types of treatment for patients with gestational trophoblastic disease.

Different types of treatment are available for patients with gestational trophoblastic disease. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Three types of standard treatment are used:

Surgery

The doctor may remove the cancer using one of the following operations:

• Dilatation and curettage (D&C) with suction evacuation: A surgical procedure to remove abnormal tissue and parts of the inner lining of the uterus. The cervix is dilated and the material inside the uterus is removed with a small vacuum-like device. The walls of the uterus are then gently scraped with a curette (spoon-shaped instrument) to remove any material that may remain in the uterus. This procedure may be used for molar pregnancies.
• Hysterectomy: Surgery to remove the uterus, and sometimes the cervix. If the uterus and cervix are taken out through the vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut) in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small incision (cut) in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy.

After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavitysuch as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated, or whether the tumor is low-risk or high-risk.

Combination chemotherapy is treatment using more than one anticancer drug.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type of gestational trophoblastic disease being treated. External radiation therapy is used to treat gestational trophoblastic disease.

New types of treatment are being tested in clinical trials.

Information about ongoing clinical trials is available from the NCI website.

Treatment for gestational trophoblastic disease may cause side effects.

For information about side effects caused by treatment for cancer, see our Side Effects page.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Blood levels of beta human chorionic gonadotropin (β-hCG) will be checked for up to 6 months after treatment has ended. This is because a β-hCG level that is higher than normal may mean that the tumor has not responded to treatment or it has become cancer.

Treatment Options for Gestational Trophoblastic Disease

• Hydatidiform Moles
• Gestational Trophoblastic Neoplasia
  • Low-risk Gestational Trophoblastic Neoplasia
  • High-risk Metastatic Gestational Trophoblastic Neoplasia
  • Placental-Site Gestational Trophoblastic Tumors and Epithelioid Trophoblastic Tumors
• Recurrent or Resistant Gestational Trophoblastic Neoplasia

Hydatidiform Moles

Treatment of a hydatidiform mole may include the following:

• Surgery (Dilatation and curettage with suction evacuation) to remove the tumor.

After surgery, beta human chorionic gonadotropin (β-hCG) blood tests are done every week until the β-hCG level returns to normal. Patients also have follow-up doctor visits monthly for up to 6 months. If the level of β-hCG does not return to normal or increases, it may mean the hydatidiform mole was not completely removed and it has become cancer. Pregnancy causes β-hCG levels to increase, so your doctor will ask you not to become pregnant until follow-up is finished.

For disease that remains after surgery, treatment is usually chemotherapy.

Gestational Trophoblastic Neoplasia

Low-risk Gestational Trophoblastic Neoplasia

Treatment of low-risk gestational trophoblastic neoplasia (GTN) (invasive mole or choriocarcinoma) may include the following:

• Chemotherapy with one or more anticancer drugs. Treatment is given until the beta human chorionic gonadotropin (β-hCG) level is normal for at least 3 weeks after treatment ends.

If the level of β-hCG in the blood does not return to normal or the tumor spreads to distant parts of the body, chemotherapy regimens used for high-risk metastatic GTN are given.

High-risk Metastatic Gestational Trophoblastic Neoplasia

Treatment of high-risk metastatic gestational trophoblastic neoplasia (invasive mole or choriocarcinoma) may include the following:

• Combination chemotherapy.
• Intrathecal chemotherapy and radiation therapy to the brain (for cancer that has spread to the lung, to keep it from spreading to the brain).
• High-dose chemotherapy or intrathecal chemotherapy and/or radiation therapy to the brain (for cancer that has spread to the brain).

Placental-Site Gestational Trophoblastic Tumors and Epithelioid Trophoblastic Tumors

Treatment of stage I placental-site gestational trophoblastic tumors and epithelioid trophoblastic tumors may include the following:

• Surgery to remove the uterus.

Treatment of stage II placental-site gestational trophoblastic tumors and epithelioid trophoblastic tumors may include the following:

• Surgery to remove the tumor, which may be followed by combination chemotherapy.

Treatment of stage III and IV placental-site gestational trophoblastic tumors and epithelioid trophoblastic tumors may include following:

• Combination chemotherapy.
• Surgery to remove cancer that has spread to other places, such as the lung or abdomen.

Recurrent or Resistant Gestational Trophoblastic Neoplasia

Treatment of recurrent or resistant gestational trophoblastic tumor may include the following:

• Chemotherapy with one or more anticancer drugs for tumors previously treated with surgery.
• Combination chemotherapy for tumors previously treated with chemotherapy.
• Surgery for tumors that do not respond to chemotherapy.

To Learn More About Gestational Trophoblastic Disease

For more information from the National Cancer Institute about gestational trophoblastic tumors and neoplasia, see the following:

• Gestational Trophoblastic Disease Home Page
• Drugs Approved for Gestational Trophoblastic Disease
• Metastatic Cancer

For general cancer information and other resources from the National Cancer Institute, see the following:

• About Cancer
• Staging
• Chemotherapy and You: Support for People with Cancer
• Radiation Therapy and You: Support for People with Cancer
• Coping with Cancer
• Questions to Ask Your Doctor about Cancer
• For Survivors and Caregivers

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