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Cancer Medicine :: Gestational Trophoblastic Tumor Treatment

Gestational Trophoblastic Tumor

Making treatment decisions

After GTD is diagnosed and staged, your medical team can recommend one or more treatment options. Choosing a treatment plan is an important decision, so be sure to take time and think about all of the choices.

No matter what type or stage of GTD a woman has, treatment is available. Your treatment choice depends on many factors. The location and the extent of the disease are very important. Other important factors include the type of GTD present, the level of human chorionic gonadotropin (HCG), duration of the disease, sites of metastasis if any, and the extent of prior treatment. In selecting a treatment plan, you and your medical team will also consider your age, general state of health, and personal preferences.

It is important to begin treatment as soon as possible after GTD has been detected. The main methods of treatment are:

Surgery

Chemotherapy

Radiation therapy (which is used less often)

Sometimes the best approach combines 2 or more of these methods.

Surgery for gestational trophoblastic disease

Suction dilation and curettage (D&C): This procedure is often used to diagnose a molar pregnancy and may be the first treatment given for a hydatidiform mole. It can be the only treatment needed. It is done in an operating room in a hospital or other type of surgical center.

Most often, general anesthesia is used (where you are asleep). Using a special instrument, the doctor enlarges (dilates) the opening of the uterus (the cervix) and then inserts a vacuum-like device that removes most of the tumor. The doctor then uses a long, spoon-like instrument (curette) to scrape the lining of the uterus to remove any molar tissue that remains. During this procedure you may receive an intravenous (IV) infusion of a drug called oxytocin. This causes the uterus to contract and expel its contents.

After the procedure, most women can go home on the same day. Potential complications of a suction D&C are not common but can include reactions to anesthesia, bleeding from the uterus, infections, scarring of the cervix or uterus, and blood clots. A rare but serious side effect is trouble breathing caused when small pieces of trophoblastic tissue break off and travel to the blood vessels in the lungs. Most women will have cramping in the pelvis and some vaginal bleeding or spotting for up to a day after the procedure.

Hysterectomy: This type of surgery removes the uterus (womb). It is an option for women with hydatidiform moles who do not want to have any more children, but it isn't often used. It is also the standard treatment for women with placental site trophoblastic tumors and epithelioid trophoblastic tumors. Removing the uterus ensures that all of the tumor cells in the uterus are gone − including any that had invaded the muscle layer (myometrium). But since some tumor cells may have already spread outside the uterus, it does not guarantee that all tumors cells are removed from the body.

The ovaries are usually left in place. Rarely, when there are theca-lutein cysts (fluid-filled sacs) in the ovaries, these cysts will be removed in an operation called an ovarian cystectomy.

There are 3 approaches to remove the uterus:

Abdominal hysterectomy: During this operation, the uterus is removed through an incision that is made in the front of the abdomen.

Vaginal hysterectomy: Less often, if the uterus is not too large, it may be detached and removed through the vagina. In some cases, the surgeon may make a small cut in the abdomen to insert a laparoscope − a long, thin instrument with a video camera on the end − to aid with the operation. This is known as a laparoscopic-assisted vaginal hysterectomy. Because there is no large abdominal incision, recovery is often quicker than with an abdominal hysterectomy.

Laparoscopic assisted vaginal hysterectomy: For this surgery, several small holes are made in the abdomen and long, thin instruments (including one with a video camera on the end) are inserted into them to perform the operation. The uterus is then removed through a small hole made in the vagina. Again, recovery is usually quicker than with an abdominal hysterectomy. As with a vaginal hysterectomy, this approach can only be used if the uterus is not too large.

For all of these operations, the patient is either asleep (general anesthesia) or sedated and numbed below the waist (regional anesthesia). A hospital stay of about 2 to 3 days is common for an abdominal hysterectomy. Complete recovery takes about 4 to 6 weeks. The usual hospital stay for a vaginal hysterectomy is 1 to 2 days with a recovery time of 2 to 3 weeks. A similar recovery is expected for a laparoscopic hysterectomy.

Hysterectomy results in the inability to have children. Some pain is common after surgery but can usually be well controlled with medicines. Complications of surgery are unusual but could include reactions to anesthesia, excessive bleeding, infection, or damage to the urinary tract, the intestine, or to nerves.

Surgery (suction D&C or hysterectomy) removes the source of disease within the uterus, but it does not get rid of cancerous cells that may have already spread outside the uterus to other parts of the body. To be certain that no cancer cells remain, blood HCG levels are carefully checked at regular time points after surgery. If HCG levels stay the same or start to rise, doctors often recommend that women receive chemotherapy. Most women with hydatidiform moles do not require chemotherapy.

Surgery for metastatic tumors

Even when GTD has spread to distant areas of the body, it can often be treated effectively with chemotherapy. But in some rare cases, surgery may be used to remove tumors in the liver, lung, brain, or elsewhere, especially if chemotherapy is not shrinking the tumor(s).

Chemotherapy for gestational trophoblastic disease

Chemotherapy (chemo) uses anti-cancer drugs that are injected into a vein or given by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers that have spread to distant organs (metastasized). GTD is one of the few cancers that can almost always be cured by chemo no matter how advanced it is. The best indicator of which drug to use is the prognostic score.

The drugs that can be used to treat GTD include: Methotrexate (with or without leucovorin), Actinomycin-D (dactinomycin), Cyclophosphamide (Cytoxan®), Chlorambucil, Vincristine (Oncovin®), Etoposide (VP-16), Cisplatin, Ifosfamide (Ifex®), Bleomycin, Fluorouracil (5-FU), Paclitaxel (Taxol®)

To reduce the risk of side effects, doctors try to give the fewest drugs at the lowest doses that will still be effective. As a general rule, women who need to get chemo and fall into the low-risk group are given a single chemo drug. Women who fall in the high-risk group usually receive combinations of drugs, often at higher doses.

Possible side effects

Chemo drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to some side effects.

The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. Common side effects of chemotherapy drugs include: Hair loss, Mouth sores, Loss of appetite, Nausea and vomiting, Low blood counts

Because chemotherapy can damage the blood-producing cells of the bone marrow, the blood cell counts might become low. This can result in:

Increased chance of infections (from too few low white blood cells)

Easy bruising or bleeding (from too few blood platelets)

Fatigue (from too few red blood cells)

Most of these side effects are short-term and tend to go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Do not hesitate to discuss any questions about side effects with the cancer care team.

Along with the effects listed above, some side effects are specific to certain medicines:

Common side effects of methotrexate are diarrhea and sores in the mouth. This drug can also cause mild liver damage which is seen as changes in certain blood tests (liver enzymes). Some women have inflammation of the eye (conjunctivitis), pain in the chest or abdomen, irritation in the genital region, or skin rash. Hair loss and blood side effects do not usually occur with single-drug methotrexate therapy.

Actinomycin-D can cause fairly severe nausea and vomiting. This can be prevented by medicines given before chemo. Treatment with actinomycin-D or combination therapy is more likely to result in hair loss. Your bone marrow's ability to produce blood cells may be affected, which in turn may lower the ability of your immune system to fight infection.

Bleomycin can cause lung problems. These occur more often in patients who smoke.

Cyclophosphamide and ifosfamide can cause some nausea and hair loss. They can also cause bladder irritation and rarely cause severe lung problems.

In rare cases, etoposide treatment has been linked with the development of leukemia several years later. Cisplatin has also been linked to this, although it occurs less often than with etoposide. But doctors still consider these drugs important to use because their benefit in curing the cancer outweighs the small risk of leukemia.

Vincristine and cisplatin can damage nerves (called neuropathy). Patients may notice tingling and numbness, particularly in the hands and feet. Cisplatin can also cause hearing loss and kidney damage. These side effects may persist after treatment stops.

You should report any side effects or changes you notice while getting chemotherapy to your medical team so that they can be treated promptly. In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.

Radiation therapy for gestational trophoblastic disease

Radiation therapy uses focused high-energy x-rays that penetrate the body to reach and destroy cancerous cells.

Radiation isn't often used to treat GTD, unless it has spread and is not responding to chemotherapy. Radiation may then be used to treat sites where the cancer may be causing pain or other problems. It may also be used when GTD has spread to the brain. If radiation is used, combination chemo is often used as well.

The type of radiation therapy most often used in treating GTD is called external beam radiation therapy. In this type of radiation therapy, the radiation is aimed at the cancer from a machine outside the body. Having this type of radiation therapy is much like having a diagnostic x-ray, except that each treatment lasts longer and the treatments are usually repeated daily over several weeks.

Treatment of gestational trophoblastic disease by type and stage

The following lists the standard treatment options according to the type of GTD and the stage and prognostic group of the disease. These treatments are discussed in more detail in separate sections about surgery, chemotherapy, and radiation therapy.

Hydatidiform moles (complete and partial moles)

The standard treatment for women who may wish to have children in the future is to remove the tumor by suction dilation and curettage (D&C). Women who no longer wish to have children usually have the option of choosing either suction D&C or hysterectomy (removal of the tumor and entire uterus). A hysterectomy ensures no tumor remains within the uterus but, like a D&C, it does not treat tumor cells that may have already spread outside the uterus.

Rarely, a hydatidiform mole occurs as part of a "twin" pregnancy, where there is a normal fetus along with the mole. In this case, the pregnancy is watched closely and typically allowed to continue. The mole is then treated after delivery.

Once the tumor is removed, a pathologist will look at it under a microscope for signs of choriocarcinoma or other malignant changes in the specimen. If there are none, then patients are carefully monitored with frequent measurements of blood HCG levels. The levels should drop and become undetectable within several months. If not, there may still be mole tissue deep in the uterus (an invasive mole) or elsewhere in the body.

Doctors recommend that women avoid becoming pregnant during the first year after diagnosis because pregnancy would raise HCG levels. Oral contraceptives may be used, but intrauterine devices (IUDs) should not be used at this time because of the risk of bleeding, infection, or other problems. Sometimes IUDs can cause problems that can look like tumor left in the uterus.

Chemotherapy (chemo) will likely be needed if the blood HCG level begins to rise or is still detectable after a reasonable time (often around 4 to 6 months), or if the pathologist finds choriocarcinoma in the tissue sample. About 1 in 5 women will need chemo after a molar pregnancy.

Stage I low-risk gestational trophoblastic tumors

This can be either persistent GTD (where the HCG level hasn't dropped to normal after treatment of a molar pregnancy) or a choriocarcinoma or placental site trophoblastic tumor that was found in the curettage specimen. The tumor is still confined to the uterus, and the prognostic score is less than 7.

Chemo with either methotrexate (with or without leucovorin/folinic acid) or actinomycin-D is the recommended treatment for stage 1, low risk disease. Hysterectomy may also be advised, particularly for women who no longer want to have babies. It may reduce the amount of chemo needed.

Chemo is given until there are no longer any signs of cancer, based on levels of HCG in the blood (the HCG level should return to normal after treatment). If the initial chemo drug does not get rid of the tumor, a second drug may be tried. If the HCG level is still detectable at this point, more intensive chemo with a combination of drugs may be needed.

Placental-site trophoblastic tumor (PSTT) is treated with hysterectomy. Chemo is usually not helpful. Since HCG is often not found at high levels in the blood with PSTT, blood levels of another hormone called human placental lactogen (hPL) may be checked and watched over time.

Epithelioid trophoblastic tumor (ETT) is also treated with hysterectomy. The HCG level may be slightly elevated, and if it is, it will be checked again after surgery. Chemo is not helpful in treating these tumors.

Stage II/lII low-risk gestational trophoblastic tumors

These tumors have spread to the genital structures or to the lungs, but the prognostic score is less than 7. Chemo with either methotrexate (with or without leucovorin) or actinomycin-D is curative in most cases. If a single drug does not get rid of the tumor, treatment with combination chemo is usually effective. In rare cases, surgical removal of the tumors plus chemo may be used. Blood HCG levels are measured after treatment and should return to normal.

PSTTs and ETTs do not respond well to chemo, so they are treated with hysterectomy (surgery to remove the uterus).

Stage II/III high-risk gestational trophoblastic tumors

These tumors have spread to the genital structures or to the lungs, and the prognostic score is 7 or higher. Standard treatment is usually an intensive combination chemo regimen such as EMA-CO (etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by cyclophosphamide and vincristine). Other drug combinations, such as EMA-EP (etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by etoposide and cisplatin), may also be used, although they may be reserved for use if the EMA-CO regimen isn't effective. In rare cases, surgical removal of the tumors plus chemo may be used. Blood HCG levels are measured after treatment and should return to normal.

PSTTs and ETTs do not respond well to chemo, so they are treated with surgery to remove the uterus (hysterectomy).

Stage IV gestational trophoblastic tumors

These tumors need intensive treatment because they have spread to distant sites such as the liver or brain. Combination chemo such as the EMA-CO regimen is the standard treatment. If the cancer has reached the brain, radiation therapy to the head is often used as well. In some cases, surgical removal of tumors may be used along with chemo. Sometimes methotrexate is given into the spinal fluid to treat tumors that have spread to the tissues around the brain and spinal cord. Again, blood HCG levels are measured after treatment and should return to normal.

PSTTs and ETTs do not respond well to chemo, so they are treated with surgery to remove the uterus and to remove tumors elsewhere in the body.

Recurrent gestational trophoblastic tumors

A tumor is called recurrent when it come backs after treatment. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). The type of treatment used depends on where the cancer recurs and what treatment the woman has already received.

For tumors that were first treated with surgery, single-drug chemotherapy may be used, unless a new risk factor puts the patient at high risk (in which case combination chemotherapy would be used). In women who have already had chemotherapy, a more intensive chemotherapy regimen would be used. Several different combinations of drugs might be tried, if needed. Again, if the cancer has reached the brain, radiation therapy to the head is often used. In some cases, surgical removal of tumors may be used as well.

Cure rates for GTD

Nearly 100% of women with complete or partial moles and low-risk GTD can be cured of their disease with appropriate treatment. PSTT has high cure rates, but the outlook isn't as good if the disease spreads outside of the uterus. Even for high-risk GTD, cure rates are as high as 80% to 90%, but will likely require more intensive treatment (combination chemotherapy, sometimes together with radiation and/or surgery).

What happens after treatment for gestational trophoblastic disease?

Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer coming back. (When cancer comes back after treatment, it is called recurrence.) This is a very common concern in people who have had cancer. It is a very real concern for some women with gestational trophoblastic disease (GTD). The risk of GTD returning is very small for molar pregnancies and low-risk GTD, but may be as high as 10% to 15% in women with high-risk GTD. For this reason, follow-up is very important.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are leading full lives. 

Follow-up doctor visits

When treatment ends, your doctors will still want to watch you closely. It is very important to go to all of your follow-up appointments. During these visits, your doctors will ask questions about any problems you may have and may do exams and lab tests or x-rays and scans to look for signs of cancer or treatment side effects. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have.

Your medical team will set up a program of follow-up visits and tests to make sure that everything is all right. The exact steps in the follow-up program depend on the type of GTD you had and the treatment you received.

In all cases, the most basic test involves measuring levels of HCG (or hPL for PSTT) in the blood. Rising HCG levels may indicate that the disease is growing again in the uterus (if hysterectomy was not done) or that it has spread to another location and is growing there. Different treatment centers follow different schedules. For molar pregnancies, blood HCG levels are usually taken weekly until the results are normal for at least 3 consecutive weeks, then monthly for at least the next 6 months. For other forms of GTD, the follow-up period may be extended to a year or 2 following treatment for those who have metastatic GTD with risk factors.

Your doctor will most likely recommend that you have a physical exam about every 3 to 6 months for the first year, then about every 6 months. Depending on your situation, you may need to have certain tests or procedures, such as chest x-rays or other imaging tests, from time to time. Ask your doctor what kind of follow-up schedule you can expect.

It is important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.

If cancer does recur, it will most likely be detected with blood HCG tests before it causes any symptoms. Still, if you notice any new symptoms you should report them right away so that the cause can be determined and treated, if needed.

If GTD does come back, in most cases it can be treated successfully. 

Avoiding pregnancy during follow-up

If you did not have a hysterectomy, it is important to avoid getting pregnant during the follow-up period. Talk with your doctor about how long this should last and whether oral contraceptives (birth control pills) or a barrier method of birth control (such as a diaphragm or condoms) might be best for you. Most doctors advise against using intrauterine devices (IUDs), as they might increase the risk of bleeding, infection, or puncturing of the uterine wall if tumor is still present.

Later pregnancies

Most women who have had a molar pregnancy can have normal pregnancies later. Studies have found that women treated for GTD have near normal risks of problems such as stillbirths, birth defects, premature babies, or other complications. However, if you do get pregnant and have had GTD once before, there is about a 1% to 2% chance that you could have another molar pregnancy. It can be a complete or partial molar pregnancy. You should have a pelvic ultrasound exam within the first 13 weeks (first trimester) of pregnancy to make sure everything is proceeding normally.

If you give birth, your doctor may request a microscopic examination of the placenta to look for any lingering signs of GTD. You will also need to have your HCG level measured about 6 weeks after the end of any subsequent pregnancy, whether it was a normal birth, abortion, or miscarriage.

Later cancers

One question many women ask is whether they are more likely to get another type of cancer later on. Having had gestational trophoblastic disease does not raise your risk of getting other cancers. However, some chemotherapy drugs sometimes used to treat GTD can increase the risk of certain other types of cancer (most often leukemia). This is rare after treatment of low-risk GTD but is slightly more common with certain drugs used for high-risk GTD, such as etoposide and cyclophosphamide.

If treatment for gestational trophoblastic disease stops working

If cancer keeps growing or comes back after one kind of treatment, it is possible that another treatment plan might still cure the cancer, or at least shrink it enough to help you live longer and feel better. But when a person has tried many different treatments and the cancer has not gotten any better, the cancer tends to become resistant to all treatment. If this happens, it's important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer − when you have been through many medical treatments and nothing's working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more chemo or radiation might have about a 1% chance of working. Some people are still tempted to try this. But it is important to think about and understand your reasons for choosing this plan.

No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose - the main purpose of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread to the bones. Or chemotherapy might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn't mean you can't have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. 

What`s new in gestational trophoblastic disease research and treatment?

Important research into gestational trophoblastic disease (GTD) is being done right now in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease and how to improve treatment.

Causes of GTD

Researchers are studying cells of GTD to learn more about how these tumors develop. Discoveries about chromosome abnormalities of complete and partial moles have helped explain the causes of these types of GTD. These discoveries have been applied to developing lab tests that can help identify these 2 types of moles (partial vs. complete) when routine microscopic analysis does not yield a clear answer.

Epidemiology

Researchers often collect data on how often various forms of cancer occur in different parts of the world and whether these diseases are becoming more or less common. This often provides clues about risk factors and ideas for prevention. Earlier studies suggested that choriocarcinoma and GTDs were 5 to 10 times more common in Asia than in Europe and North America. More recent information indicates that the difference is no greater than double and may be even less, and that the original estimates were likely biased by differences in the way births are recorded in different countries.

Staging and prognosis

Newer and more sensitive tests are now able to more accurately determine blood human chorionic gonadotropin (HCG) levels than in the past. Scientists have developed a blood test for a form of HCG known as hyperglycosylated HCG. Early studies suggest that this blood test may help separate patients with active GTD who need treatment from those who have elevated HCG levels but don't truly have GTD, and therefore may not require therapy. More studies are needed to confirm this.

Improvements in the staging systems and prognostic classification systems are making it easier for doctors to recognize which patients will benefit from which treatments.

Treatment

In recent years, a number of studies have shown the value of using combination chemotherapy for high-risk metastatic GTD, such as the EMA-CO and EMA-EP regimens. The excellent results with these regimens have made them treatments of choice in many institutions.

Newer chemotherapy drugs including pemetrexed, paclitaxel, and gemcitabine are also being studied for use in this disease, as are several new combinations of drugs. Some of these are already in use in women whose GTD doesn't respond to other treatments.

For tumors that are resistant to standard chemotherapy doses, doctors are studying the use of high-dose chemotherapy followed by a stem cell transplant to restore the patient's bone marrow. Some very early results have been promising, but more research is needed.

Researchers are also studying ways to give the usual chemotherapy drugs with new schedules that might be more effective, cause less severe side effects, and/or be more convenient for patients.

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