21st Century Adult Cancer Sourcebook: Gestational Trophoblastic Tumors, Hydatidiform Mole, Choriocarcinoma, GTD, GTT, GTN, PSTT - Clinical Data for Patients, Families, and Physicians
Edition 1.0 - October 2011
National Cancer Institute
Smashwords Edition
Copyright 2011 Progressive Management
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PART ONE
Chapter 1A: Gestational Trophoblastic Tumors Patient Information
Chapter 2A: Gestational Trophoblastic Tumors Health Professional Information
Chapter 3A: Gestational Trophoblastic Tumors NCI Drugs
Chapter 4A: Gestational Trophoblastic Tumors Clinical Trials
PART TWO
Chapter 1B: Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (NCI)
Chapter 2B: Glossary of Clinical Trial Terms
Chapter 3B: Clinical Trials Background Information
Chapter 4B: Cancer Clinical Trials -The Basic Workbook
Chapter 5B: Cancer Clinical Trials - The In-Depth Program
Chapter 6B: Clinical Trials at NIH
Chapter 7B: How To Find A Cancer Treatment Trial: A Ten Step Guide
Chapter 8B: Taking Part in Cancer Treatment Research Studies
Chapter 9B: Cancer Clinical Trials
Chapter 10B: Access to Investigational Drugs
Chapter 12B: Taking Time: Support for People with Cancer
Chapter 13B: Facing Forward - Life After Cancer Treatment
Chapter 14B: Chemotherapy and You
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PART ONE
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Chapter 1A: Gestational Trophoblastic Tumors Patient Information
Gestational Trophoblastic Tumors Treatment
Patient Version
Last Modified: 07/29/2011
Definition of gestational trophoblastic tumor: Any of a group of tumors that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. The two main types of gestational trophoblastic tumors are hydatidiform mole and choriocarcinoma. Also called gestational trophoblastic disease.
Description
What are gestational trophoblastic tumors?
Gestational trophoblastic tumor, a rare cancer in women, is a disease in which cancer (malignant) cells grow in the tissues that are formed following conception (the joining of sperm and egg). Gestational trophoblastic tumors start inside the uterus, the hollow, muscular, pear-shaped organ where a baby grows. This type of cancer occurs in women during the years when they are able to have children. There are two types of gestational trophoblastic tumors: hydatidiform mole and choriocarcinoma.
If a patient has a hydatidiform mole (also called a molar pregnancy), the sperm and egg cells have joined without the development of a baby in the uterus. Instead, the tissue that is formed resembles grape-like cysts. Hydatidiform mole does not spread outside of the uterus to other parts of the body.
If a patient has a choriocarcinoma, the tumor may have started from a hydatidiform mole or from tissue that remains in the uterus following an abortion or delivery of a baby. Choriocarcinoma can spread from the uterus to other parts of the body. A very rare type of gestational trophoblastic tumor starts in the uterus where the placenta was attached. This type of cancer is called placental-site trophoblastic disease.
Gestational trophoblastic tumor is not always easy to find. In its early stages, it may look like a normal pregnancy. A doctor should be seen if there is vaginal bleeding (not menstrual bleeding) and if a woman is pregnant and the baby hasn’t moved at the expected time.
If there are symptoms, a doctor may use several tests to see if the patient has a gestational trophoblastic tumor. An internal (pelvic) examination is usually the first of these tests. The doctor will feel for any lumps or strange feeling in the shape or size of the uterus. The doctor may then do an ultrasound, a test that uses sound waves to find tumors. A blood test will also be done to look for high levels of a hormone called beta-HCG (beta human chorionic gonadotropin) which is present during normal pregnancy. If a woman is not pregnant and HCG is in the blood, it can be a sign of gestational trophoblastic tumor.
The chance of recovery (prognosis) and choice of treatment depend on the type of gestational trophoblastic tumor, whether it has spread to other places, and the patient’s general state of health.
Glossary Terms
beta-human chorionic gonadotropin (BAY-tuh-HYOO-mun KOR-ee-AH-nik goh-NA-doh-TROH-pin)
* A hormone normally found in the blood and urine during pregnancy. It may also be produced by some tumor cells. An increased level of beta-human chorionic gonadotropin may be a sign of cancer of the testis, uterus, ovary, liver, stomach, pancreas, or lung. Beta-human chorionic gonadotropin may also be produced in response to certain conditions that are not cancer. Beta-human chorionic gonadotropin is being studied in the treatment of Kaposi sarcoma. Also called beta-hCG.
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood chemistry study (blud KEH-mih-stree STUH-dee)
* A procedure in which a sample of blood is examined to measure the amounts of certain substances made in the body. An abnormal amount of a substance can be a sign of disease in the organ or tissue that produces it.
cancer (KAN-ser)
* A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
choriocarcinoma (KOR-ee-oh-KAR-sih-NOH-muh)
* A malignant, fast-growing tumor that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta). Almost all choriocarcinomas form in the uterus after fertilization of an egg by a sperm, but a small number form in a testis or an ovary. Choriocarcinomas spread through the blood to other organs, especially the lungs. They are a type of gestational trophoblastic disease. Also called chorioblastoma, chorioepithelioma, and chorionic carcinoma.
cyst (sist)
* A sac or capsule in the body. It may be filled with fluid or other material.
gestational trophoblastic tumor (jeh-STAY-shuh-nul troh-fuh-BLAS-tik TOO-mer)
* Any of a group of tumors that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. The two main types of gestational trophoblastic tumors are hydatidiform mole and choriocarcinoma. Also called gestational trophoblastic disease.
hormone (HOR-mone)
* One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.
malignant (muh-LIG-nunt)
* Cancerous. Malignant cells can invade and destroy nearby tissue and spread to other parts of the body.
menstrual cycle (MEN-stroo-ul SY-kul)
* The monthly cycle of hormonal changes from the beginning of one menstrual period to the beginning of the next.
molar pregnancy (MOH-ler PREG-nun-see)
* A slow-growing tumor that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. A molar pregnancy contains many cysts (sacs of fluid). It is usually benign (not cancer) but it may spread to nearby tissues (invasive mole). It may also become a malignant tumor called choriocarcinoma. Molar pregnancy is the most common type of gestational trophoblastic tumor. Also called hydatidiform mole.
organ (OR-gun)
* A part of the body that performs a specific function. For example, the heart is an organ.
pelvic examination (PEL-vik eg-ZA-mih-NAY-shun)
* A physical examination in which the health care professional will feel for lumps or changes in the shape of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The health care professional will also use a speculum to open the vagina to look at the cervix and take samples for a Pap test. Also called internal examination.
placenta (pluh-SEN-tuh)
* The organ that nourishes the developing fetus in the uterus.
prognosis (prog-NO-sis)
* The likely outcome or course of a disease; the chance of recovery or recurrence.
sperm (spurm)
* The male reproductive cell, formed in the testicle. A sperm unites with an egg to form an embryo.
stage
* The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
symptom (SIMP-tum)
* An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
tumor (TOO-mer)
* An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
ultrasound (UL-truh-SOWND)
* A procedure in which high-energy sound waves are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. Also called ultrasonography.
uterus (YOO-teh-rus)
* The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called womb.
vaginal (VA-jih-nul)
* Having to do with the vagina (the birth canal).
Stage Explanation
Once gestational trophoblastic tumor has been found, more tests will be done to find out if the cancer has spread from inside the uterus to other parts of the body (staging). Treatment of gestational trophoblastic tumor depends on the stage of the disease and the patient’s age and general health. The following stages are used for gestational trophoblastic tumor:
Hydatidiform mole
Cancer is found only in the space inside the uterus. If the cancer is found in the muscle of the uterus, it is called an invasive mole (choriocarcinoma destruens).
Placental-site gestational trophoblastic tumors
Cancer is found in the place where the placenta was attached and in the muscle of the uterus.
Nonmetastatic
Cancer cells have grown inside the uterus from tissue remaining following treatment of a hydatidiform mole or following an abortion or delivery of a baby. Cancer has not spread outside the uterus.
Metastatic, good prognosis
Cancer cells have grown inside the uterus from tissue remaining following treatment of a hydatidiform mole or following an abortion or delivery of a baby. The cancer has spread from the uterus to other parts of the body. Metastatic gestational trophoblastic tumors are considered good prognosis or poor prognosis.
Metastatic gestational trophoblastic tumor is considered good prognosis if all of the following are true:
* The last pregnancy was less than 4 months ago.
* The level of beta-HCG in the blood is low.
* Cancer has not spread to the liver or brain.
* The patient has not received chemotherapy earlier.
Metastatic, poor prognosis
Cancer cells have grown inside the uterus from tissue remaining following treatment of a hydatidiform mole or following an abortion or delivery of a baby. The cancer has spread from the uterus to other parts of the body. Metastatic gestational trophoblastic tumors are considered good prognosis or poor prognosis.
Metastatic gestational trophoblastic tumor is considered poor prognosis if any the following are true:
* The last pregnancy was more than 4 months ago.
* The level of beta-HCG in the blood is high.
* Cancer has spread to the liver or brain.
* The patient received chemotherapy earlier and the cancer did not go away.
* The tumor began after the completion of a normal pregnancy.
Recurrent
Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the uterus or in another part of the body.
Glossary Terms
beta-human chorionic gonadotropin (BAY-tuh-HYOO-mun KOR-ee-AH-nik goh-NA-doh-TROH-pin)
* A hormone normally found in the blood and urine during pregnancy. It may also be produced by some tumor cells. An increased level of beta-human chorionic gonadotropin may be a sign of cancer of the testis, uterus, ovary, liver, stomach, pancreas, or lung. Beta-human chorionic gonadotropin may also be produced in response to certain conditions that are not cancer. Beta-human chorionic gonadotropin is being studied in the treatment of Kaposi sarcoma. Also called beta-hCG.
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
cancer (KAN-ser)
* A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
choriocarcinoma (KOR-ee-oh-KAR-sih-NOH-muh)
* A malignant, fast-growing tumor that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta). Almost all choriocarcinomas form in the uterus after fertilization of an egg by a sperm, but a small number form in a testis or an ovary. Choriocarcinomas spread through the blood to other organs, especially the lungs. They are a type of gestational trophoblastic disease. Also called chorioblastoma, chorioepithelioma, and chorionic carcinoma.
gestational trophoblastic tumor (jeh-STAY-shuh-nul troh-fuh-BLAS-tik TOO-mer)
* Any of a group of tumors that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. The two main types of gestational trophoblastic tumors are hydatidiform mole and choriocarcinoma. Also called gestational trophoblastic disease.
liver (LIH-ver)
* A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.
metastatic (meh-tuh-STA-tik)
* Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.
placenta (pluh-SEN-tuh)
* The organ that nourishes the developing fetus in the uterus.
prognosis (prog-NO-sis)
* The likely outcome or course of a disease; the chance of recovery or recurrence.
recur
* To come back or to return.
recurrent cancer (ree-KER-ent KAN-ser)
* Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.
stage
* The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
staging (STAY-jing)
* Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
tumor (TOO-mer)
* An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
uterus (YOO-teh-rus)
* The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called womb.
Treatment Option Overview
How gestational trophoblastic tumor is treated
Different types of treatment are available for patients with gestational trophoblastic tumor. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. 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. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Two kinds of standard treatment are used: surgery (taking out the cancer) and chemotherapy (using drugs to kill cancer cells). Radiation therapy (using high-energy x-rays to kill cancer cells) may be used in certain cases to treat cancer that has spread to other parts of the body.
The doctor may take out the cancer using one of the following operations:
* Dilation and curettage (D & C) with suction evacuation is stretching the opening of the uterus (the cervix) and removing the material inside the uterus with a small vacuum-like device. The walls of the uterus are then scraped gently to remove any material that may remain in the uterus. This is used only for molar pregnancies.
* Hysterectomy is an operation to take out the uterus. The ovaries usually are not removed in the treatment of this disease.
Chemotherapy uses drugs to kill cancer cells. It may be taken by pill or put into the body by a needle in a vein or muscle. It is called a 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.
Radiation therapy uses high-energy x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from putting materials that produce radiation (radioisotopes) through thin plastic tubes into the area where the cancer cells are found (internal radiation).
Treatment 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.
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. In the following lists of treatments for the different stages, a link to search results for current clinical trials is included for each section. These have been retrieved from NCI’s clinical trials database. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Glossary Terms
cancer (KAN-ser)
* A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cervix (SER-vix)
* The lower, narrow end of the uterus that forms a canal between the uterus and vagina.
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
clinical trial (KLIH-nih-kul TRY-ul)
* A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
dilation and curettage (dy-LAY-shun … kyoo-reh-TAZH)
* A procedure to remove tissue from the cervical canal or the inner lining of the uterus. The cervix is dilated (made larger) and a curette (spoon-shaped instrument) is inserted into the uterus to remove tissue. Also called D&C and dilatation and curettage.
drug (drug)
* Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
external-beam radiation therapy (...RAY-dee-AY-shun THAYR-uh-pee)
* A type of radiation therapy that uses a machine to aim high-energy rays at the cancer from outside of the body. Also called external radiation therapy.
gestational trophoblastic tumor (jeh-STAY-shuh-nul troh-fuh-BLAS-tik TOO-mer)
* Any of a group of tumors that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. The two main types of gestational trophoblastic tumors are hydatidiform mole and choriocarcinoma. Also called gestational trophoblastic disease.
hysterectomy (HIS-teh-REK-toh-mee)
* Surgery to remove the uterus and, sometimes, the cervix. When the uterus and the cervix are removed, it is called a total hysterectomy. When only the uterus is removed, it is called a partial hysterectomy.
internal radiation therapy (in-TER-nul RAY-dee-AY-shun THAYR-uh-pee)
* A type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor. Also called brachytherapy, implant radiation therapy, and radiation brachytherapy.
molar pregnancy (MOH-ler PREG-nun-see)
* A slow-growing tumor that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. A molar pregnancy contains many cysts (sacs of fluid). It is usually benign (not cancer) but it may spread to nearby tissues (invasive mole). It may also become a malignant tumor called choriocarcinoma. Molar pregnancy is the most common type of gestational trophoblastic tumor. Also called hydatidiform mole.
NCI
* NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.
ovary (OH-vuh-ree)
* One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.
radiation (RAY-dee-AY-shun)
* Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
* The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
radioisotope (RAY-dee-oh-I-suh-tope)
* An unstable form of a chemical element that releases radiation as it breaks down and becomes more stable. Radioisotopes may occur in nature or be made in a laboratory. In medicine, they are used in imaging tests and in treatment. Also called radionuclide.
recur
* To come back or to return.
side effect (side eh-FEKT)
* A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.
stage
* The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
standard therapy (... THAYR-uh-pee)
* Treatment that experts agree is appropriate, accepted, and widely used. Also called best practice, standard medical care, and standard of care.
surgery (SER-juh-ree)
* A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
systemic therapy (sis-TEH-mik THAYR-uh-pee)
* Treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body.
tumor (TOO-mer)
* An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
uterus (YOO-teh-rus)
* The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called womb.
x-ray (EX-ray)
* A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.
Table of Links
1 http://www.cancer.gov/cancertopics/druginfo/gestationaltumors
Hydatidiform Mole
Treatment may be one of the following:
* Removal of the mole using dilation and curettage (D & C) and suction evacuation.
* Surgery to remove the uterus (hysterectomy).
Following surgery, the doctor will follow the patient closely with regular blood tests to make sure the level of beta-HCG in the blood falls to normal levels. If the blood level of beta-HCG increases or does not go down to normal, more tests will be done to see whether the tumor has spread. Treatment will then depend on whether the patient has nonmetastatic disease or metastatic disease (see the treatment sections on metastatic or nonmetastatic disease).
Placental-Site Gestational Trophoblastic Tumors
Treatment will probably be surgery to remove the uterus (hysterectomy).
Nonmetastatic Gestational Trophoblastic Tumors
Treatment may be one of the following:
* Chemotherapy.
* Surgery to remove the uterus (hysterectomy) if the patient no longer wishes to have children.
Good Prognosis Metastatic Gestational Trophoblastic Tumors
Treatment may be one of the following:
* Chemotherapy.
* Surgery to remove the uterus (hysterectomy) followed by chemotherapy.
* Chemotherapy followed by hysterectomy if cancer remains following chemotherapy.
Poor Prognosis Metastatic Gestational Trophoblastic Tumors
Treatment will probably be chemotherapy. Radiation therapy may also be given to places where the cancer has spread, such as the brain.
Recurrent Gestational Trophoblastic Tumors
Treatment will probably be chemotherapy.
* * * * * * * * * * * *
Chapter 2A: Gestational Trophoblastic Tumors Health Professional Information
Gestational Trophoblastic Tumors and Neoplasia Treatment
General Information About Gestational Trophoblastic Tumors and Neoplasia
Gestational trophoblastic tumors (GTTs) and neoplasias (GTNs) are rare but highly curable tumors arising from the products of conception in the uterus.
GTTs include:
• Choriocarcinoma.
• Placental-site trophoblastic tumor (very rare).
• Epithelioid trophoblastic tumor (even more rare).
GTNs include:
• GTTs.
• Persistence of complete or partial gestational hydatidiform moles.
• Invasive moles.
All of these entities are grouped under the term gestational trophoblastic disease (GTD). The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia).[1J However, at least part of this variability is caused by differences in diagnostic criteria and reporting. The reported incidence in the United States is about 110 to 120 per 100,000 pregnancies. The reported incidence of choriocarcinoma, the most aggressive form of GTT, in the U.S. is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.[1]
Two factors have consistently been associated with an increased risk of GTD:[1J
• Maternal age.
• Prior history of hydatidiform mole (HM).
If a woman has been previously diagnosed with an HM, she carries a 1% risk of HM in subsequent pregnancies. This increases to approximately 25% with more than one prior HM. The risk associated with maternal age is bimodal, with increased risk both for mothers younger than 20 years and older than 35 years (and particularly for mothers >45 years). Relative risks are in the range of 1.1 to 11 for both the younger and older age ranges compared to ages 20 years to 35 years. However, a population-based HM registry study suggests that the age-related patterns of the two major types of HM—complete and partial HM (see Cellular Classification section below)—are distinct.[2] In that study, the rate of complete HM was highest in women younger than 20 years, then decreasing monotonically with age. However, the rates of partial HM increased for the entire age spectrum, suggesting possible differences in etiology. The association with paternal age is inconsistent.[1J A variety of exposures have been examined, with no clear associations found with tobacco smoking, alcohol consumption, diet, and oral contraceptive use.[i]
GTDs contain paternal chromosomes and are placental, rather than maternal, in origin. The most common presenting symptoms are vaginal bleeding and a rapidly enlarging uterus, and GTD should be considered whenever a premenopausal woman presents with these findings. Since the vast majority of GTD types are associated with elevated human chorionic gonadotropin (hCG) levels, an hCG blood level and pelvic ultrasound are the initial steps in the diagnostic evaluation. In addition to vaginal bleeding and uterine enlargement, other presenting symptoms or signs may include:
• Pelvic pain or sensation of pressure.
• Anemia.
• Hyperemesis gravidarum.
• Hyperthyroidism (secondary to the homology between the b-subunits of hCG and thyroid-stimulating hormone (TSH), which causes hCG to have weak TSH-like activity).
• Preeclampsia early in pregnancy.
The most common antecedent pregnancy in GTN is that of an HM.
Choriocarcinoma most commonly follows a molar pregnancy but can follow a normal pregnancy, ectopic pregnancy, or abortion, and it should always be considered when a patient has continued vaginal bleeding in the postdelivery period. Other possible signs include neurologic symptoms (resulting from brain metastases) in a female within the reproductive age group and asymptomatic lesions on routine chest x-ray.
The prognosis for cure of patients with GTTs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM staging system has limited prognostic value.[3] The probability of cure depends on the following:
• Histologic type (mole, invasive mole, or choriocarcinoma).
• Extent of spread of the disease/largest tumor size.
• Level of serum bhCG.
• Duration of disease from the initial pregnancy event to start of treatment.
• Number and specific sites of metastases.
• Nature of antecedent pregnancy.
• Extent of prior treatment.
Selection of treatment depends on these factors plus the patient's desire for future pregnancies. The bhCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.
References
1. Altieri A, Franceschi S, Ferlay J, et al.: Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 4 (11): 670-8, 2003.
2. Altman AD, Bentley B, Murray S, et al.: Maternal age-related rates of gestational trophoblastic disease. Obstet Gynecol 112 (2 Pt 1): 244-50, 2008.
3. Gestational trophoblastic tumors. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 439.
Cellular Classification of Gestational Trophoblastic Tumors and Neoplasia
* HM - Complete HM * Partial HM
* Invasive Mole
* Gestational Trophoblastic Neoplasias - Choriocarcinoma * PSTT * Epithelioid trophoblastic tumor
Gestational trophoblastic tumors (GTTs) and neoplasias (GTNs) may be classified as follows:[1J
• Hydatidiform mole (HM) - Complete HM - Partial HM.
• Invasive mole (chorioadenoma destruens).
• GTN - Choriocarcinoma -Placental-site trophoblastic tumor (PSTT; very rare) - Epithelioid trophoblastic tumor (ETT; even more rare).
HM
HM is defined as products of conception that show gross cyst-like swellings of the chorionic villi that are caused by an accumulation of fluid. There is disintegration and loss of blood vessels in the villous core.
Complete HM
A complete mole occurs when an ovum that has extruded its maternal nucleus is fertilized by either a single sperm, with subsequent chromosome duplication, or two sperm, resulting in either case in a diploid karyotype. The former case always yields a mole with a karyotype of 46 XX, since at least one X chromosome is required for viability and a karyotype of 46 YY is rapidly lethal to the ovum. The latter case may yield a karyotype of 46 XX or 46 XY. About 90% of complete HMs are 46 XX. On ultrasound examination, complete moles rarely reveal a fetus or amniotic fluid.
Partial HM
A partial mole occurs when the ovum retains its nucleus but is fertilized by a single sperm, with subsequent chromosome duplication, or is fertilized by two sperm; the possible resulting triploid karyotypes are 69 XXY, 69 XXX, or 69 XYY. Therefore, in contrast to a complete mole, the partial mole chromosomes of a partial mole are only two-thirds paternal in origin. In contrast to complete moles, partial moles usually show a fetus, which may even be viable, and amniotic fluid is visible.
Complete HMs have a 15% to 25% risk of developing into GTNs, but transformation to malignancy is much more rare (<5%) in the case of partial moles.
Invasive Mole
Invasive moles (chorioadenoma destruens) are locally invasive, rarely metastatic lesions characterized microscopically by trophoblastic invasion of the myometrium with identifiable villous structures. They are usually diploid in karyotype, but may be aneuploid. Microscopically, these lesions are characterized by hyperplasia of cytotrophoblastic and syncytial elements and persistence of villous structures. They may resemble choriocarcinoma in histologic appearance. Invasive moles have more aggressive behavior than either complete or partial HMs, and they are treated similarly to choriocarcinoma (i.e., with chemotherapy). However, unlike choriocarcinoma, they may regress spontaneously.
Gestational Trophoblastic Neoplasias
Choriocarcinoma
Choriocarcinoma is a malignant tumor of the trophoblastic epithelium. Uterine muscle and blood vessels are invaded with areas of hemorrhage and necrosis. Columns and sheets of trophoblastic tissue invade normal tissues and spread to distant sites, the most common of which are lungs, brain, liver, pelvis, vagina, spleen, intestines, and kidney. Most choriocarcinomas have an aneuploid karyotype, and about three-quarters contain a Y chromosome. Most follow an HM pregnancy, spontaneous abortion, or ectopic pregnancy; but about one-quarter are preceded by a full-term pregnancy. Nearly all GTNs that are preceded by nonmolar pregnancies are choriocarcinomas; the rare exceptions generally are placental-site trophoblastic tumors (PSTTs).
PSTT
PSTT disease is the result of a very rare tumor arising from the placental implantation site and resembles an exaggerated form of syncytial endometritis. Trophoblastic cells infiltrate the myometrium, and there is vascular invasion. Human placental lactogen is present in the tumor cells, whereas immunoperoxidase staining for human chorionic gonadotropin (hCG) is positive in only scattered cells, and elevations in serum hCG are relatively low compared with the marked elevations seen in choriocarcinoma. hCG is not a reliable marker of tumor volume.[l,2] PSTTs have much lower growth rates than choriocarcinoma, and presentation after a full-term pregnancy is often delayed by months or years. They are generally resistant to chemotherapy. Therefore, hysterectomy is the standard primary treatment if the tumor is confined to the uterus. However, about 35% of PSTTs have distant metastases at diagnosis.[2,3] Common sites of metastasis include the lungs, pelvis, and lymph nodes. Central nervous system, renal, and liver metastases have also been observed.