A gestational trophoblastic tumor (GTT) is a rare cancer that occurs in women. A GTT is most commonly the result of an abnormal pregnancy due to an abnormal combination of a sperm and an egg. In other cases, a GTT is a cancerous growth that begins from a normal placenta (the organ that develops during pregnancy and connects the fetus [unborn baby] to the uterus).
There are three types of GTTs:
Hydatidiform mole. Also called a molar pregnancy, this type accounts for about 80% of all GTTs. There are two main types of molar pregnancy: a complete molar pregnancy and a partial molar pregnancy. A complete molar pregnancy begins when a sperm fertilizes an abnormal egg. Instead of forming an embryo, the tissue grows into a mound of cells that look like grape-like cysts; there is no evidence of normal fetal development. Partial molar pregnancy begins with fertilization of an egg by two sperm. It has some of the features of a complete molar pregnancy, but also has some fetal development. The fetus has abnormal chromosomes and has no potential for survival. Another type of molar pregnancy is the invasive molar pregnancy, which most commonly begins from a complete molar pregnancy, but can also arise from a partial molar pregnancy. Most hydatidiform moles do not spread outside of the uterus. In fewer than 15% of molar pregnancies, there is evidence of spread outside of the uterus.
Choriocarcinoma. This type of GTT may begin as a hydatidiform mole or from the placenta, whether through delivery of a baby, abortion (induced termination of a pregnancy), or miscarriage (uninduced termination of a pregnancy). Choriocarcinoma can spread outside of the uterus. About 5% of all GTTs are choriocarcinomas.
Placental-site trophoblastic disease. This rare type of GTT can start in the placenta.
Statistics
Overall, GTTs are rare. In the United States, GTTs account for less than 1% of all gynecologic cancers. A hydatidiform mole may develop in one in 1,000 pregnancies and 10% to 17% of these cases become malignant (cancerous). Choriocarcinoma is rare, occurring one pregnancy out of 20,000 to 40,000 in the United States. Molar pregnancies occur much more often in Asian countries than in the United States. GTTs are typically curable, especially if found early.
Cancer statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States, but the actual risk for a particular individual may differ. It is not possible to tell a woman how long she will live with a GTT. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.
A risk factor is anything that increases a person’s chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices
The following factors may raise a woman’s risk of developing a GTT:
Age. Being younger than 20 or older than 40 when becoming pregnant.
Previous molar pregnancy. A previous molar pregnancy may increase the risk of developing a GTT.
Nutrition/diet. Low levels of carotene and vitamin A in a person’s diet may be associated with a higher risk of molar pregnancy.
Lower socioeconomic status. Lower socioeconomic status may be associated with GTT because of poor nutrition.
Blood type. The blood type of each parent may increase the risk of GTT. For example, the risk is increased if the woman has blood type A and the man has blood type O.
Women with a GTT may experience the following symptoms. Sometimes, women with a GTT do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your doctor.
A GTT may not cause any symptoms in its early stage because it may resemble a normal pregnancy. However, the following symptoms could signal a potential problem:
Vaginal bleeding
A pregnancy where the baby has not moved at the expected time
A larger than expected uterine size
Pregnancy-associated high blood pressure at an early point in the pregnancy
Choriocarcinoma or a placental site trophoblastic tumor may cause a wide variety of symptoms, including vaginal bleeding after an apparent normal delivery. Symptoms may appear after a normal birth weeks, months, or even years in rare situations.
Rarely, the diagnosis of a GTT is made when the cancer spreads to other organs, causing specific symptoms depending on the location. In this case, another disease may first be thought to cause the symptoms, as a diagnosis of GTT may not be obvious. For example, spread of choriocarcinoma to the brain may result in bleeding, which can be mistaken for a brain aneurysm. A beta human chorionic gonadotropin (beta hCG) blood test (see Diagnosis) should help to clarify the diagnosis.
Doctors use many tests to diagnose cancer and determine if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
The type of cancer suspected
Severity of symptoms
Previous test results
In addition to a physical examination, the following tests may be used to diagnose a GTT:
Pelvic examination. The doctor may feel the uterus, vagina, ovaries, fallopian tubes, bladder, and rectum to check for lumps or any unusual changes.
Ultrasound. An ultrasound uses sound waves to create a picture of the internal organs. In a transvaginal ultrasound, an ultrasound wand is inserted into the vagina and aimed at the uterus, to obtain the pictures.
Beta hCG blood test. Women who are pregnant produce high levels of beta hCG in their blood. High levels of beta hCG in a woman who is not pregnant could mean that a GTT is present.
X-ray. An x-ray is a picture of the inside of the body. For instance, a chest x-ray can help doctors determine if the cancer has spread to the lungs.
Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein to provide better detail.
Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer's stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis (chance of recovery). There are different stage descriptions for different types of cancer.
One tool that doctors use to describe the stage is the TNM system. This system uses three criteria to judge the stage of the cancer: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to the rest of the body. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer so doctors can work together to plan the best treatments.
TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Typically in most types of cancer, doctors look at these three factors to determine the stage of cancer:
How large is the primary tumor and where is it located? (Tumor, T)
Has the tumor spread to the lymph nodes? (Node, N)
Has the cancer metastasized to other parts of the body? (Metastasis, M)
However, traditional staging does not adequately describe the staging of a GTT; therefore, to stage a GTT, the “N” or node category is removed and replaced with a risk factor score (see below). This score serves to further stage the tumor into low-risk and high-risk categories.
Tumor. The "T" plus a letter or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. This helps the doctor develop the best treatment plan for each individual. Specific tumor stage information is listed below:
TX: The primary tumor cannot be evaluated.
T0 (T plus zero): There is no tumor.
T1: The tumor is only in the uterus.
T2: The tumor has invaded other reproductive structures, such as the ovaries, vagina, or broad ligaments, by either metastasis or direct tumor growth.
Distant metastasis. The “M” indicates whether the cancer has spread to other parts of the body.
MX: Distant metastasis cannot be evaluated.
M0 (M plus zero): There is no distant metastasis.
M1: There is metastasis to other parts of the body.
M1a: There is metastasis to the lungs.
M1b: There is metastasis to any other area of the body.
World Health Organization (WHO) Risk Score
The table below is used to illustrate the risk score staging factor. Low risk is a score of 7 or less, and high risk is a score of 8 or greater.
Risk Score
Prognostic Factor
0
1
2
4
Age
Younger than 40
40 and/or older
Previous pregnancy
Hydatidiform mole
Abortion
Full-term pregnancy
Months since last pregnancy
Less than 4
4 to 6
7 to 12
More than 12
Pretreatment hCG (IU/ml)
Less than 10³
Greater than or equal to 10³ to 104
104 to 105
Greater than or equal to 105
Largest tumor size, including uterus
Less than 3 cm
3 to 5 cm
Greater than or equal to 5 cm
Site of spread
Lung
Spleen, kidney
Gastrointestinal tract
Brain, liver
Number of tumors that have spread
1 to 4
5 to 8
More than 8
The number of drugs used to treat the cancer that have not worked
Single drug
Two or more drugs
Total Score
GTT Stage Grouping
For a GTT, doctors assign the stage by combining the T and M classifications and include a risk factor score.
Stage I: The tumor is only in the uterus and has not spread, and the patient has an unknown-risk score (T1, M0, Unknown risk).
Stage IA: The tumor is only in the uterus and has not spread, and the patient has a low-risk score (T1, M0, Low risk).
Stage IB: The tumor is only in the uterus and has not spread, and the patient has a high-risk score (T1, M0, High risk).
Stage II: The tumor has spread to other reproductive structures but has not spread elsewhere, and the patient has an unknown-risk score (T2, M0, Unknown risk).
Stage IIA: The tumor has invaded other reproductive structures but has not spread elsewhere, and the patient has a low-risk score (T2, M0, Low risk).
Stage IIB: The tumor has invaded other reproductive structures but has not spread elsewhere, and the patient has a high-risk score (T2, M0, High risk).
Stage III: The tumor is of any size and has spread to the lungs, and the patient has an unknown-risk score (Any T, M1a, Unknown risk).
Stage IIIA: The tumor is of any size and has spread to the lungs, and the patient has an unknown-risk score (Any T, M1a, Low risk).
Stage IIIB: The tumor is of any size and has spread to the lungs, and the patient has a high-risk score (Any T, M1a, High risk).
Stage IV: The tumor is of any size and has spread to other parts of the body beyond the lungs, and the patient has an unknown-risk score (Any T, M1a, Unknown risk).
Stage IVA: The tumor is of any size and has spread to other parts of the body beyond the lungs, and the patient has a low-risk score (Any T, M1a, Low risk).
Stage IVB: The tumor is of any size and has spread to other parts of the body beyond the lungs, and the patient has a high-risk score (Any T, M1a, High risk).
Recurrent: Recurrent cancer is cancer that comes back after treatment.
Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002)published by Springer-Verlag New York, www.springer-ny.com.
The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) uses the following staging system for GTT.
Stage I: The tumor is limited to the uterus.
Stage II: The tumor includes local metastases to the pelvis and vagina.
Stage III: The tumor involves pulmonary (lung) metastases.
Stage IV: The tumor consists of distant metastatic disease.
The treatment of a GTT depends on the size and location of the tumor, whether the cancer has spread, and the woman’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. Surgery, chemotherapy, and radiation therapy may all be used to treat a woman with a GTT.
This section outlines treatments that are the standard of care (best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the clinical trials section.
Surgery
Surgery may range from dilation and curettage (D&C) to hysterectomy, depending on the stage of the tumor. D&C is the removal of the contents of the uterus with a small vacuum-like device, then the walls of the uterus are scraped to remove any material that remains. A D&C is used for a molar pregnancy. A hysterectomy is the removal of the uterus and is used to treat a more advanced tumor.
Following surgery, the woman’s beta hCG level will be monitored with blood tests to make sure it falls into normal levels. If the beta hCG level remains high or increases after an initial drop, it may mean that cancer cells are still present; either in a portion of the original tumor (called a persistent or invasive mole) and/or there is spread to another area. If this occurs, additional treatment will be recommended.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Similar to surgery, the type of chemotherapy depends on the stage of the GTT. A low-risk invasive mole or metastatic disease often can be treated successfully with methotrexate (multiple brand names) either alone or in combination with leucovorin (Wellcovorin). Another drug that can be used is dactinomycin (Cosmegen, Lyovac Cosmegen). Approximately 15% of women with low-risk disease will need treatment with a second drug for treatment to be successful.
Women with high-risk metastatic disease generally receive combination chemotherapy. The most common treatment is a combination called EMA-CO (etoposide [VePesid, Etopophos, Lastet], methotrexate, dactinomycin, cyclophosphamide [Cytoxan, Neosar], and vincristine [Oncovin]). Cisplatin (Platinol) with vincristine and methotrexate has been successful to treat women with a tumor that did not go into remission (a temporary or permanent absence of symptoms) with the above-mentioned treatments.
Treatment results are measured by beta hCG levels. Usually treatment is continued until beta hCG levels are normal, and then one to two additional cycles of treatment may be given.
The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.
Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy.
Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.
Doctors and scientists are always looking for better ways to treat patients with a GTT. A clinical trial is a way to test a new treatment to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.
Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress in treating GTTs. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with a GTT.
To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.
Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.
Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your health-care team. Before treatment begins, talk with your doctor about possible side effects of the specific treatment you will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of cancer, its location, the individual treatment plan (including the length and dosage of treatment), and the person’s overall health.
Ask your doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health-care team if they do happen. Also, be sure to communicate with the doctor about side effects you experience during and after treatment. For more information on the most common side effects of cancer and different treatments, along with ways to prevent or control them, visit Cancer.Net’s section on Managing Side Effects, based on ASCO’s curriculum.
In addition to physical side effects, there may be psychosocial (emotional and social) effects are well. Learn more about the importance of addressing these needs in Cancer.Net’s section on Caring for the Whole Patient.
For more information on late effects or long-term effects, please read the After Treatment section or talk with your doctor.
After treatment for a GTT ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years.
Follow-up treatment includes measuring beta hCG levels every one to two weeks until the hormone level is normal for three consecutive tests. After that, beta hCG levels should be monitored monthly for the first year, every four months for the second year, then yearly for the third and fourth years. Women are encouraged to talk with their doctors about the recommended amount of time to wait before becoming pregnant after reaching normal levels of beta hCG. If the woman had either a complete or partial molar pregnancy and no chemotherapy was given, pregnancy may be safe after three to six months. Also, patients with a history of a GTT should have a beta hCG check after each pregnancy, even if the pregnancy was completely normal.
Women recovering from a GTT are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.
Research for GTT is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all diagnostic and treatment options with your doctor.
New drugs that impair various processes in the cancer cell, including topoisomerase-I inhibitors (drugs that interfere with the replication of DNA, which affects cancer cell growth), angiogenesis inhibitors (drugs that stop the formation of blood vessels needed for the tumor to grow and spread), and microtubule agents (drugs that disrupt the structure of cancer cells), are being tested to treat GTTs. In addition, researchers are also studying the use of growth factors added to chemotherapy
Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:
What is the exact type of GTT that I have?
Can you explain my pathology report (laboratory test results) to me?
What is the stage of the tumor? What does this mean?
What are my treatment options?
What clinical trials are open to me?
What treatment do you recommend? Why?
What are the possible side effects of this treatment, both in the short term and the long term?
Will I be able to have children after treatment?
How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
What are the chances that the GTT will recur?
What follow-up tests will I need, and how often will I need them?
What support services are available to me? To my family?
Women’s Cancer Network
Gynecologic Cancer Foundation
230 W. Monroe, Ste. 2528
Chicago, IL 60606
Phone: 312-578-1439
Toll Free: 800-444-4441 www.wcn.org
Rare Cancer Alliance
1649 N. Pacana Way
Green Valley, AZ 85614
Toll Free: 800-345-6324
Phone: 206-600-5327 www.rare-cancer.org
National Organization for Rare Disorders
55 Kenosia Ave.
P.O. Box 1968
Danbury, CT 06813-1968
Toll Free: 800-999-6673 (voice mail only)
Phone: 203-744-0100 www.rarediseases.org
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