Gestational Trophoblastic Disease The body is made up of hundreds of millions of living cells.

Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries. Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell. Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesn't die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does. People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found. In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow. Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body. No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer. Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

Not all tumors are cancerous. Tumors that aren't cancer are called benign. Benign tumors can cause problems they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they can't invade, they also can't spread to other parts of the body (metastasize). These tumors are almost never life threatening. What is gestational trophoblastic disease? Gestational trophoblastic disease (GTD) is a group of rare tumors that involve abnormal growth of cells inside a woman's uterus. GTD does not develop from cells of the uterus like cervical cancer or endometrial (uterine lining) cancer do. Instead, these tumors start in the cells that would normally develop into the placenta during pregnancy. (The term "gestational" refers to pregnancy.) GTD begins in the layer of cells called the trophoblast that normally surrounds an embryo. (Tropho- means "nutrition," and -blast means "bud" or "early developmental cell.") Early in normal development, the cells of this layer form tiny, finger-like projections known as villi. These villi grow into the lining of the uterus. In time, the trophoblast layer develops into the placenta, the organ that protects and nourishes the growing fetus. Most GTDs are benign (non cancerous) and they don't invade deeply into body tissues or spread to other parts of the body. But some are cancerous. Because not all of these tumors are cancerous, this group of tumors may be referred to as gestational trophoblastic disease, gestational trophoblastic tumors, or gestational trophoblastic neoplasia. (The wordneoplasia simply means "new growth.") All forms of GTD can be treated. And in most cases the treatment produces a complete cure.

Types of gestational trophoblastic disease The main types of gestational trophoblastic diseases are: hydatidiform mole (complete or partial) invasive mole choriocarcinoma placental site trophoblastic tumor Hydatidiform mole The most common form of GTD is called a hydatidiform mole, also known as a molar pregnancy. It is made up of villi that have become swollen with fluid. The swollen villi grow in clusters that look like bunches of grapes. This is called a molar "pregnancy," but it is not possible for a normal baby to form. Hydatidiform moles are not cancerous, but they may develop into cancerous GTDs. There are 2 types of hydatidiform moles: complete and partial.

A complete hydatidiform mole most often develops when either 1 or 2 sperm cells fertilize an "empty" egg cell (a cell that contains no nucleus or DNA). All the genetic material comes from the father's sperm cell. Therefore, there is no fetal tissue. Surgery can totally remove most complete moles, but in as many as 1 in 5 women there will be some persistent molar tissue (see the section, "Persistent gestational trophoblastic disease"). Most often this is an invasive mole, but in rare cases it is a choriocarcinoma, a malignant (cancerous) form of GTD. In either case it will require further treatment. A partial hydatidiform mole develops when 2 sperm fertilize a normal egg. These tumors contain some fetal tissue, but this is often mixed in with the trophoblastic tissue. It is important to know that a viable (able to live) fetus is not being formed. Partial moles are usually completely removed by surgery. Only a small number of women with partial moles need further treatment after initial surgery. Partial moles rarely develop into malignant GTD. Persistent gestational trophoblastic disease is a term used to describe GTD that is not cured by initial surgery. Persistent GTD occurs when the hydatiform mole has grown from the surface layer of the uterus into the muscle layer below (called the myometrium). The surgery used to treat a hydatiform mole (called suction dilation and curettage, or D&C) involves scraping the inside of the uterus. This removes only the inner layer of the uterus and cannot remove tumor that has grown into the muscular layer. Most cases of persistent GTD are invasive moles, but in rare cases they are choriocarcinomas or placental site trophoblastic tumors (see below). Invasive mole An invasive mole (formerly known as chorioadenoma destruens) is a hydatidiform mole that has grown into the muscle layer of the uterus (the myometrium). Invasive moles can develop from either complete or partial moles, but complete moles become invasive much more often than partial moles. Invasive moles develop in a little less than 1 out of 5 women who have had a complete mole removed. The risk of developing an invasive mole in these women increases if: menstrual period and treatment. The uterus has become very large. The woman is older than 40 years. The woman has had GTD in the past. Because these moles have grown into the uterine muscle layer, they aren't completely removed during a D&C. Invasive moles can sometimes go away on their own, but most often more treatment is needed.

A tumor or mole that grows completely through the myometrium may result in bleeding into the abdominal or pelvic cavity. This bleeding can be life threatening. In about 15% of cases, the tumor spreads (metastasizes) to other parts of the body, most often the lungs. Choriocarcinoma Choriocarcinoma is a malignant form of GTD. It is much more likely than other types of GTD to grow quickly and spread to organs away from the uterus. Choriocarcinoma most often develops from a complete hydatidiform mole, but it can also occur after a partial mole, a normal pregnancy, or a pregnancy that ends early (such as a miscarriage or an elective abortion). Rarely, choriocarcinomas can develop that are not related to pregnancy. These can be found in areas other than the uterus, and can occur in both men and women. They may develop in the ovaries, testicles, chest, or abdomen. In these cases, choriocarcinoma is usually mixed with other types of cancer, forming a type of cancer called a mixed germ cell tumor. These tumors are not considered to be gestational (related to pregnancy) and are not discussed in this document. Non-gestational choriocarcinoma can be less responsive to chemotherapy and may have a less favorable prognosis (outlook) than gestational choriocarcinoma. For more information about these tumors, see our documents, Ovarian Cancer and Testicular Cancer. Placental site trophoblastic tumor Placental site trophoblastic tumor (PSTT) is a very rare form of GTD that develops where the placenta attaches to the uterus. This tumor most often develops after a normal pregnancy or abortion, but it may also develop after a complete or partial mole is removed. Most PSTTs do not spread to other sites in the body. But these tumors have a tendency to grow into (invade) the muscle layer of the uterus. Most forms of GTD are very sensitive to chemotherapy drugs, but PSTTs are not. Instead, they are treated with surgery, aimed at completely removing disease. What are the key statistics about gestational trophoblastic disease? Hydatidiform moles occur in about 1 pregnancy out of 1,000 in the United States and Europe. In very rare cases (less than 1%), a normal fetus can develop along with the hydatidiform mole. In about 15% of cases, a hydatidiform mole will progress to become an "invasive" mole. Overall, invasive moles occur at an estimated rate of 1 pregnancy in 15,000. Choriocarcinoma, a malignant form of GTD, is even less common, affecting approximately 1 pregnancy out of 40,000

in the United States. Like other forms of GTD, choriocarcinoma is more common in many Asian and African countries. About 2% to 4% of hydatidiform moles progress to become choriocarcinoma. But only half of all gestational choriocarcinomas start off as molar pregnancies. About onequarter of all choriocarcinomas develop in women who have a miscarriage (spontaneous abortion), intentional abortion, or tubal pregnancy (the fetus develops in the fallopian tube, rather than in the uterus). Another one-quarter occur after normal pregnancy and delivery. Overall, gestational trophoblastic tumors account for less than 1% of female reproductive system cancers. Cure rates depend on the type of GTD and its stage, as described in the section "How is gestational trophoblastic disease treated?" What are the risk factors for gestational trophoblastic disease? A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx (voice box), bladder, kidney, and several other organs. But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may not have any known risk factors. Even if a person has a risk factor, it is often very hard to know how much that risk factor may have contributed to the cancer. Researchers have found several risk factors that may increase a woman's chance of developing gestational trophoblastic disease (GTD).

Prior miscarriage(s) or problems getting pregnant Women with either of these have a higher risk of GTD, although their overall risk is still low. Blood type Women with blood type A or AB are at slightly higher risk than those with type B or O.

Birth control pills Women who take birth control pills may be more likely to get GTD when they do become pregnant. The link between the use of birth control pills and GTD is weak, and may be explained by other factors. This risk seems to be higher for women who took the pills longer. But the risk is still so low that it doesn't outweigh the benefit of using the pills.

Socioeconomic status Some studies have found that lower socioeconomic status is linked with an increased risk, although the reasons for this are not clear. Some researchers have suggested that diet may play a role.

Diet A few studies have found that a low level of beta-carotene (a nutrient converted to vitamin A in the body) in the diet may be linked with a higher risk of complete molar pregnancies. More research is needed to confirm this.

Family history Very rarely, several women in the same family have one or more molar pregnancies. Do we know what causes gestational trophoblastic disease? All forms of gestational trophoblastic disease (GTD) begin after an egg cell is fertilized by a sperm cell. Normally, the sperm and egg cells each provide a set of 23 chromosomes (bits of DNA that contain our genes) to create a cell with 46 chromosomes. This cell will start dividing to eventually become a fetus. In complete hydatidiform moles, the problem most often arises when a sperm cell fertilizes an abnormal egg cell that contains no nucleus (or chromosomes). The reason the egg contains no chromosomes is not known. After fertilization, the chromosomes from the sperm duplicate themselves, so there are 2 copies of identical chromosomes that both come from the sperm. When this happens, normal development cannot occur, and no fetus is formed. Instead, a complete hydatidiform mole develops. Less often, a complete mole

Age Gestational trophoblastic disease occurs in women of childbearing age. The risk of complete molar pregnancy is highest in women over age 40 and younger than 20. The risk is even higher for women over the age of 50, in whom onethird of pregnancies results in a complete hydatiform mole. Age is less a factor for partial moles.

Prior molar pregnancy Once a woman has had a hydatidiform mole, she has a higher risk of having another one. The overall risk for later pregnancies is about 1% to 2%. This risk increases further if she has a history of more than one molar pregnancy.

forms when an abnormal egg without any chromosomes is fertilized by 2 sperm cells. Again, there are 2 copies of the father's chromosomes and none from the mother, and no fetus forms. Partial hydatidiform moles result when 2 sperm cells fertilize a normal egg at the same time. The fertilized egg contains 3 sets of chromosomes (69) instead of the usual 2 sets (46). An embryo with 3 sets of chromosomes cannot grow into a fully developed infant. This situation leads to an abnormal (malformed) fetus along with some normal placental tissue and a partial hydatidiform mole. Invasive moles are hydatidiform moles that begin to grow into the muscle layer of the uterus. They develop more often from complete moles than from partial moles. It's not clear exactly what causes this to happen. Most choriocarcinomas develop from persistent hydatidiform moles (usually complete moles). They can also develop when bits of tissue are left behind in the uterus after a spontaneous (miscarriage), an intended abortion, or the delivery of a baby following an otherwise normal pregnancy. Researchers have found changes in certain genes that are commonly found in choriocarcinoma cells, but it's not clear what causes these changes. Can gestational trophoblastic disease be prevented? The only way to avoid the rare chance of developing gestational trophoblastic disease (GTD) is to not get pregnant.. But GTD is so rare that its prevention should not be a factor in family planning decisions. Women with a prior history of one or more molar pregnancies should speak with their doctor to be sure they understand their risk for future molar pregnancies. Can gestational trophoblastic disease be found early? Most cases of gestational trophoblastic disease (GTD) are found early during routine prenatal care. Usually, a woman has certain signs and symptoms, like vaginal bleeding, that suggest something may be wrong. (These symptoms are discussed in the section, "How is gestational trophoblastic disease diagnosed?") These signs will prompt the doctor to look for the cause of trouble. Often, moles or tumors cause swelling in the uterus that seems like a normal pregnancy. But a doctor can usually tell that this isn't a normal pregnancy during a routine ultrasound exam. A blood test for human chorionic gonadotropin (HCG) can also show that something is abnormal. This substance is normally elevated in the blood of pregnant women, but it may be very high if there is GTD. Fortunately, even if it is not detected early, GTD is a very treatable (and usually curable) form of cancer. Because women who have had one molar pregnancy are at increased risk, doctors can be especially careful in checking their future pregnancies with beta-HCG tests and transvaginal or pelvic sonograms. (These tests are described in the next section.)

How is gestational trophoblastic disease diagnosed? Gestational trophoblastic disease (GTD) is most often found either as a result of abnormal signs or symptoms during pregnancy or from the results of certain tests during routine prenatal care.

Signs and symptoms It's important to let your doctor know about any abnormal symptoms you are having during pregnancy. Your doctor may suspect that gestational trophoblastic disease (GTD) is present based on a typical pattern of signs and symptoms. Many of these may also be caused by conditions other than GTD. Still, if you have any of these, it's important to see your doctor right away so the cause can be found and treated, if needed. Complete hydatidiform moles (molar pregnancies) Most of these signs and symptoms (except for bleeding), are seen less commonly now than in the past because they tend to occur late in the course of the disease. Most women with GTD are now diagnosed early because of the use of blood tests and ultrasound early in pregnancy. Vaginal bleeding: Almost all women with complete hydatidiform moles have irregular vaginal bleeding during pregnancy. It occurs a little less often with partial moles. Bleeding typically starts during the first trimester (13 weeks) of pregnancy. Women with GTD often pass blood clots or watery brown discharge from the vagina. Sometimes, pieces of the mole resembling a cluster of grapes become dislodged from the uterus and are discharged through the vagina. Anemia: In cases of serious or prolonged bleeding, a woman's body is not able to replace red blood cells as fast as they are lost. This can lead to anemia (low red blood cell counts). Symptoms can include fatigue and shortness of breath, especially with physical activity. Abdominal swelling: The uterus and abdomen tend to get bigger faster in a complete molar pregnancy than they do in a normal pregnancy. Abnormal uterine enlargement occurs in about 1 out 4 women with complete moles but rarely in women with partial moles. Vomiting: Many women have nausea and vomiting during the course of a typical pregnancy. With GTD, however, the vomiting may be more frequent and severe than normal. Pre-eclampsia: Pre-eclampsia (toxemia of pregnancy) can occur as a complication of a normal pregnancy (usually in the third trimester). When it occurs earlier in pregnancy (like during the first or early second trimester), it can be a sign of a complete molar pregnancy. Pre-eclampsia may cause problems such as high blood pressure, headache, exaggerated reflexes, swelling in the hands or feet, and too much protein leaking into the urine. It affects a small number of women with complete moles but is rare in women with partial moles. Hyperthyroidism: Hyperthyroidism (having an overactive thyroid gland) occurs in some women with complete

hydatidiform moles. Symptoms of hyperthyroidism can include rapid heartbeat, warm skin, sweating, problems tolerating heat, and mild tremors (shaking). This occurs in less than 10% of women with complete molar pregnancy. Partial hydatiform moles The signs and symptoms of partial hydatidiform moles are similar to those of complete moles, but often are less severe. Some symptoms, such as frequent vomiting or an overactive thyroid gland, rarely, if ever, occur with partial moles. Partial moles are often diagnosed after what is thought to be a miscarriage. The molar pregnancy is found when the uterus is scraped during a dilation and curettage (D & C) and the products of conception are looked at under a microscope. Invasive moles and choriocarcinoma These more invasive forms of GTD sometimes develop after a complete mole has been removed. They occur less commonly after a partial mole. Choriocarcinoma can also develop after a normal pregnancy, ectopic pregnancy (where the fetus grows outside of the uterus, such as inside a fallopian tube), or miscarriage. Symptoms can include: Bleeding: The most common symptom is vaginal bleeding. Rarely, the tumor grows through the uterine wall, which can cause bleeding into the abdominal cavity along with severe abdominal pain. Infection: In larger tumors, some of the tumor cells may die, creating an area where bacteria can grow. Infection may develop, which can cause vaginal discharge, crampy pelvic pain, and fever. Abdominal swelling: Like hydatidiform moles, more invasive forms of GTD can expand the uterus, causing abdominal swelling. Human chorionic gonadotropin (HCG), a hormone made by the tumor (see below), may cause fluid-filled cysts (called theca lutein cysts) to form in the ovaries, which can be large and may also contribute to abdominal swelling. Lung symptoms: The lung is a common site for distant spread of GTD. Spread to the lungs may cause coughing up of blood, a dry cough, chest pain, or trouble breathing. Vaginal mass: These tumors can sometimes spread to the vagina, which can cause vaginal bleeding or a pus-like discharge. The doctor may also notice a cancerous growth on the vagina during a pelvic exam. Other symptoms of distant spread: Symptoms depend on where the spread occurs. If GTD has spread to the brain, symptoms can include headache, vomiting, dizziness, seizures, or paralysis on one side of the body. Spread to the liver can cause abdominal pain and a yellowing of the skin or eyes (jaundice). Placental site trophoblastic tumors Placental site trophoblastic tumors rarely spread to distant sites. More often, they grow into the wall of the uterus Bleeding: As with other forms of GTD, the most common symptom is vaginal bleeding. If the tumor grows all the way

through the wall of the uterus, it can cause bleeding into the abdominal cavity with severe abdominal pain. Abdominal swelling: As they grow within the wall of the uterus, they may cause the uterus to enlarge. Blood and urine tests Blood and urine tests can be used to help diagnose GTD. Human chorionic gonadotropin (HCG) Trophoblastic cells of both normal placentas and GTD make a hormone called human chorionic gonadotropin (HCG), which is vital in supporting a pregnancy. HCG is released into the blood, and some of it is excreted in the urine. This hormone consists of 2 chemical components, and the commonly-used blood and urine tests measure one of these, called beta-HCG (HCG). HCG is normally found only in the blood or urine of pregnant women. In fact, finding HCG in urine is the basis of most pregnancy tests. A complete mole usually releases more HCG than a normal placenta, so finding higher than expected HCG levels in the blood can be a sign that a complete mole is present. However, not all women with GTD have HCG levels that are higher than those seen in a normal pregnancy. For example, most women with partial moles or placental site trophoblastic tumors have normal or only slightly increased HCG levels. HCG tests can also help tell if GTD may be present after a pregnancy or miscarriage, as the level of HCG should normally fall to an undetectable level soon afterward. Along with helping to diagnose GTD, blood HCG levels are also very useful in women already known to have GTD. They can be used to: help estimate the amount of GTD present in a patient's body. Higher levels of HCG may mean that more tumor cells are present in the body. determine if treatment is working. HCG levels should drop to normal levels after treatment. detect GTD that has come back after treatment It's especially important to monitor HCG levels during treatment and follow-up to make sure the disease has gone away or has not returned. The HCG test is generally very accurate. In rare cases, patients may have abnormal substances (antibodies) in their blood that interfere with the HCG test. When these patients' blood samples are tested, the HCG levels appear higher than they really are, a situation known as phantom HCG. In some cases, women have been diagnosed with GTD when it is not actually present. A sign of

phantom HCG is having high blood levels of HCG, but normal urine levels (because the abnormal antibodies are not present in urine). If doctors notice that the blood (or serum) levels of HCG are high but the urine levels are not, they can order special tests to distinguish between truly elevated HCG levels and phantom HCG. Other blood tests Other tests may provide indirect evidence of GTD. For example, red blood cell counts can detect anemia (having too few red blood cells), which can be caused by uterine bleeding. Human placental lactogen (hPL) is a marker that may be used to follow patients with PSTT. For women diagnosed with GTD, blood tests are often used to watch for side effects from chemotherapy. Blood cell counts are done to watch the health of the bone marrow (where new blood cells are made), and blood chemistry tests can be used to check the condition of the liver and kidneys.

the ultrasound may show a "twin" pregnancy in which one of the twins is a normal fetus and the other is a hydatidiform mole. This occurs less than 1% of the time. In a partial molar pregnancy, ultrasound can show an abnormally formed placenta. If a fetus is seen, it is often deformed. Ultrasound is also used to help find out if a mole is invading local tissues. If blood levels of HCG are still elevated after the mole has been removed, more exams may need to be done. Chest x-ray A chest x-ray may be done in cases of persistent GTD to see if it has spread to your lungs, which is very unlikely unless your cancer is far advanced. However, CT scans of the chest are done more often if your doctor suspects persistent or advanced disease. Either test can be done in any outpatient setting. Computed tomography (CT) scan The CT scan is an x-ray test that produces detailed crosssectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. A computer then combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body. Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called "oral contrast." This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body. The injection may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Medicine can be given to prevent and treat allergic reactions. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for xrays. CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken. This test may be done to see if the GTD has spread outside the uterus, such as the lungs, brain, or liver. If your doctor suspects the GTD has spread to any of these sites, a CT or MRI scan may be done. Magnetic resonance imaging (MRI) scan

Imaging tests Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done to help find out whether a tumor is present and to learn how far it may have spread. Ultrasound (sonogram) Ultrasound can identify most cases of GTD, and will likely be the first test done if your doctor suspects there may be a problem. How it works: This test uses sound waves to produce images of internal organs. A small microphone-like instrument called a transducer gives off sound waves and then picks up the echoes they make as they bounce off body tissues. The echoes are converted into a black and white image by a computer. That image is then displayed on a computer screen. What it's like to have the test: Ultrasound is an easy procedure. It uses no radiation, which is why it is often used to look at developing fetuses. During an ultrasound exam, you simply lie on a table while a technician or doctor moves the transducer on the part of your body being examined. Most ultrasounds are done with the transducer placed on the skin after it is first lubricated with gel. To diagnose GTD, a different type of ultrasound called transvaginal ultrasonography is most often used. In this procedure, a small transducer is placed into the vagina. This allows for good images of the uterus for women suspected of having GTD during the first trimester of their pregnancy. What doctors look for: In a normal pregnancy, ultrasound imaging shows a picture of the developing fetus inside the womb. In a complete molar pregnancy, however, no fetus can be seen on an ultrasound. Instead, the ultrasound detects the large, grape-like swollen villi that are typical of GTD. Rarely,

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details. MRI scans are a little more uncomfortable than CT scans. First, they take longer -- often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). Newer, "open" MRI machines can sometimes help with this if needed. The machine also makes buzzing and clicking noises that you may find disturbing. Some centers provide headphones with music to block this out. MRI scans are most helpful in looking at the brain and spinal cord. They are most likely to be used if persistent GTD has already been found to have spread elsewhere, such as to the lungs. Positron emission tomography (PET) scan PET scans involve injecting a form of radioactive sugar (known as fluorodeoxyglucose or FDG) into the blood. The amount of radioactivity used is very low. Cancer cells in the body grow rapidly, so they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your whole body. PET scans are sometimes useful if your doctor thinks the cancer may have spread (or returned after treatment) but doesn't know where. PET scans can be used instead of several different imaging tests because they scan your whole body. These tests are rarely used for GTD. Some newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the radiologist to compare areas of higher radioactivity on the PET with the appearance of that area on the CT.

chromosomes of the mole. Other tests may look at certain genes that only come from the mother to see if it is a partial mole versus a complete mole. (D&C is described in the section, "How is gestational trophoblastic disease treated?") How is gestational trophoblastic disease staged? Staging is the process of finding out how far a cancer has spread. This information helps doctors choose the type of treatment that offers the best possible results. Molar pregnancies (complete and partial moles) are usually completely removed during a D&C (or, rarely, a hysterectomy), so they don't need to be surgically "staged". Staging is more useful for persistent GTDs, including invasive moles and choriocarcinomas.

Gestational trophoblastic disease (GTD) classification The stage of most cancers depends on how large they are and whether they have spread to lymph nodes or distant sites. This is part of staging for GTD as well (and is described below). But because treatment is usually effective regardless of the extent of the disease, other factors such as a woman's age, length of time from the pregnancy, and HCG level are more useful in predicting a woman's outlook (prognosis). These factors are taken into account in a scoring system. Prognostic scoring system In the United States, most cancer centers use a system that describes women with persistent GTDs according to their prognosis, based on several factors. Age Younger than 40 40 or older Score 0 1

Preceding pregnancy Molar pregnancy Abortion (includes miscarriage)

Score 0 1 2

Other tests Doctors can often be fairly certain of a diagnosis of GTD based on symptoms, blood test results, and imaging tests, but the diagnosis is often made after a D&C in patients with abnormal bleeding. The cells from the tumor are removed and viewed under a microscope. The cells from different types of GTD each look different under the microscope. Sometimes complete and partial moles may be hard to tell apart when they are examined under the microscope early in the first trimester. If so, other tests may be needed to distinguish the 2 types of mole. Some tests, called cytogenetics, look at the number and type of Birth (term pregnancy)

Time since pregnancy Less than 4 months More than 4 months but less than 7 months

Score 0 1

7 - 13 months More than 13 months

2 4

More than 8

Prior failed chemotherapy? None Blood HCG level (IU/L) before treatment Less than 1,000 1,000 - 9,999 10,000 - 99,999 100,000 or more Score 0 1 2 4 Single drug 2 or more drugs

Score 0 2 4

The numbers are then added up, and the overall score determines a woman's risk level. Women with a score of 7 or less are at low risk and tend to have a good outlook regardless of how far the cancer has spread. The tumor(s) will usually respond well to chemotherapy. Women with a score of 8 or more are at high risk, and their tumors tend to respond less well to chemotherapy, even if they haven't spread much. They may require more intensive chemotherapy. FIGO anatomic staging The International Federation of Gynecology and Obstetrics (FIGO) has developed a staging system based on the extent of the GTD as follows: Stage I: The tumor is still within the uterus. Stage II: The tumor has grown outside of the uterus to involve other genital structures (like the vagina or ovaries). It has not spread outside the pelvis. Stage III: The tumor has spread to the lungs; it may or may not also involve genital structures such as the vagina or vulva. Stage IV: The tumor has spread to distant organs such as the brain, liver, kidneys, and/or gastrointestinal tract. Stage grouping Stage grouping is a process that some doctor use that combines the prognostic score and the anatomic stage. This is listed as the anatomic stage, followed by the letter A if the prognostic score was low risk or B if the prognostic score resulted in high risk. Stage IA: The tumor has not spread outside the uterus, and the prognostic score puts you at low risk. Stage IB: The tumor has not spread outside the uterus, and the prognostic score puts you at high risk. Stage IIA: The tumor has grown outside of the uterus but not beyond the vagina or pelvis, and the prognostic score puts you at low risk. Stage IIB: The tumor has grown outside of the uterus but not beyond the vagina or pelvis, and the prognostic score puts you at high risk.

Largest tumor size, including the original one in the uterus Less than 3 cm (1.2 inches) across Between 3 cm and 5 cm 5 cm (2 inches) or more

Score 0 1 2

Site of metastases (if any) Lung Spleen, kidney Gastrointestinal tract Brain, liver

Score 0 1 2 4

Number of metastases found 0 14 58

Score 0 1 2

Stage IIIA: The tumor has spread to the lungs, and may or may not also involve genital structures such as the vagina or vulva. The prognostic score puts you at low risk. Stage IIIB: The tumor has spread to the lungs, and may or may not also involve genital structures such as the vagina or vulva. The prognostic score puts you at high risk. Stage IVA: The cancer has spread to distant organs such as the brain, liver, kidneys, and/or gastrointestinal tract. The prognostic score puts you at low risk. Stage IVB: The cancer has spread to distant organs such as the brain, liver, kidneys, and/or gastrointestinal tract. The prognostic score puts you at high risk. How is gestational trophoblastic disease treated? This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience. The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options. The first part of this section describes the various types of treatments used for gestational trophoblastic disease (GTD). This information is followed by a description of the most common approaches used for these cancers based on the type and classification of GTD.

Surgery 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. Suction D&C is often the choice for women who may want to have children in the future. 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. Most women will have cramping 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. Removing the uterus ensures that all of the tumor cells in the uterus, including any that had invaded the myometrium, are gone. But since some tumor cells may have already spread outside the uterus at the time of surgery, 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: This is the most common type of hysterectomy for treating GTD. During this operation, the uterus is removed through an incision 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,

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, and less frequently radiation therapy. Sometimes the best approach uses a combination of 2 or more of these methods.

recovery is often quicker than with an abdominal hysterectomy. Laparoscopic 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. 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, wound infection, or damage to the urinary or intestinal systems. 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 observed after surgery. If HCG levels don't go down 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).

cyclophosphamide chlorambucil vincristine (Oncovin) etoposide cisplatin 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 (see the section, "How is gestational trophoblastic disease staged?") are given a single chemo drug. Women who fall in the high-risk group usually receive combinations of drugs, often at higher doses. Single drug treatment Methotrexate: Chemotherapy with methotrexate alone can be used in most women with low risk disease. The methotrexate can be given as an injection into a vein or a muscle every day for 5 days. This can be repeated again after a rest period based on the HCG level. Another way to give methotrexate is to give a larger dose once a week. Again, the treatment is continued as long as needed based on the HCG level. Another option is to give methotrexate along with folinic acid (also called leucovorin). Leucovorin is not a chemo drug, but instead is a type of vitamin that reduces the side effects of methotrexate. In this course of treatment, methotrexate is given on days 1, 3, 5, and 7, and leucovorin is given on days 2, 4, 6, and 8. Each cycle has 8 days of drug treatment, followed by a rest period. This method involves more treatment days, so it may be less convenient, and the rate of resistance may be slightly higher than with methotrexate given on a daily basis. In all cases, methotrexate is given in cycles that are repeated until blood levels of HCG remain normal for a few weeks. Vitamins such as folic acid should not be taken with methotrexate unless directed by your doctor. Actinomycin-D: Another option is to give actinomycin-D (dactinomycin) instead of methotrexate. This drug may be especially useful in patients with liver problems, because it is less toxic to the liver than methotrexate is. Actinomycin-D can be given in a vein (intravenously, or IV) every day for 5 days, followed by several days without treatment. It is also given as a larger single dose once every 2 weeks. This schedule seems to have fewer side effects while still working well. Either way, the cycles are repeated until HCG levels have stayed in the normal range for several weeks. Combinations of drugs Women with higher-risk disease will receive combinations of drugs such as methotrexate, actinomycin-D, and cyclophosphamide. Other drugs such as etoposide, vincristine, and cisplatin may also be used.

Chemotherapy 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 drugs that can be used to treat GTD include: methotrexate (with or without leucovorin) actinomycin-D (also known as dactinomycin)

Some of the more commonly used combinations include: MAC: methotrexate/leucovorin, actinomycin-D, and cyclophosphamide or chlorambucil EMA-CO: etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by cyclophosphamide and vincristine (Oncovin) EMA-EP: etoposide, methotrexate/leucovorin, and actinomycin-D, followed a week later by etoposide and cisplatin VBP: vinblastine, bleomycin, and cisplatin 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 increased chance of infections (due to low white blood cell counts) easy bruising or bleeding (due to low blood platelet counts) fatigue (due to low red blood cell counts) 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 experience 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 medications 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. Cyclophosphamide can cause some nausea and hair loss. It can also cause bladder irritation. In rare cases, etoposide treatment has been linked with the development of leukemia several years later. But doctors still consider it important to use because its 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 is stopped. 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 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 chemo. Then radiation may 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. Clinical trials You may have had to make a lot of decisions since you've been told you have cancer. One of the most important decisions you will make is choosing which treatment is best for you. You may have heard about clinical trials being done

for your type of cancer. Or maybe someone on your health care team has mentioned a clinical trial to you. Clinical trials are carefully controlled research studies that are done with patients who volunteer for them. They are done to get a closer look at promising new treatments or procedures. If you would like to take part in a clinical trial, you should start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service for a list of clinical trials that meet your medical needs. You can reach this service at 1-800-303-5691 or on our Web site at http://clinicaltrials.cancer.org. You can also get a list of current clinical trials by calling the National Cancer Institute's Cancer Information Service toll-free at 1-800-4CANCER (1-800-422-6237) or by visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials. There are requirements you must meet to take part in any clinical trial. If you do qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it. Clinical trials are one way to get state-of-the art cancer treatment. They are the only way for doctors to learn better methods to treat cancer. Still, they are not right for everyone. You can get a lot more information on clinical trials in our document called Clinical Trials: What You Need to Know. You can read it on our Web site or call our toll-free number (1800-227-2345) and have it sent to you. Complementary and alternative therapies When you have cancer you are likely to hear about ways to treat your cancer or relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to Internet groups and Web sites offer ideas for what might help you. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few. What exactly are complementary and alternative therapies? Not everyone uses these terms the same way, and they are used to refer to many different methods, so it can be confusing. We use complementary to refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor's medical treatment. Complementary methods: Most complementary treatment methods are not offered as cures for cancer. Mainly, they are used to help you feel better. Some methods that are used along with regular treatment are meditation to reduce stress, acupuncture to help relieve pain, or peppermint tea to relieve nausea. Some complementary methods are known to help, while others have not been tested. Some have been proven not be helpful, and a few have even been found harmful. Alternative treatments: Alternative treatments may be offered as cancer cures. These treatments have not been

proven safe and effective in clinical trials. Some of these methods may pose danger, or have life-threatening side effects. But the biggest danger in most cases is that you may lose the chance to be helped by standard medical treatment. Delays or interruptions in your medical treatments may give the cancer more time to grow and make it less likely that treatment will help. Finding out more It is easy to see why people with cancer think about alternative methods. You want to do all you can to fight the cancer, and the idea of a treatment with no side effects sounds great. Sometimes medical treatments like chemotherapy can be hard to take, or they may no longer be working. But the truth is that most of these alternative methods have not been tested and proven to work in treating cancer. As you consider your options, here are 3 important steps you can take: Look for "red flags" that suggest fraud. Does the method promise to cure all or most cancers? Are you told not to have regular medical treatments? Is the treatment a "secret" that requires you to visit certain providers or travel to another country? Talk to your doctor or nurse about any method you are thinking about using. Contact us at 1-800-227-2345 to learn more about complementary and alternative methods in general and to find out about the specific methods you are looking at. The choice is yours Decisions about how to treat or manage your cancer are always yours to make. If you want to use a non-standard treatment, learn all you can about the method and talk to your doctor about it. With good information and the support of your health care team, you may be able to safely use the methods that can help you while avoiding those that could be harmful.

Treatment of GTD 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, like a suction D&C, ensures no tumor remains within the uterus but 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 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 chemotherapy 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 7 or less. Chemotherapy with either methotrexate (with or without leucovorin) or actinomycin-D is the recommended treatment for persistent moles and choriocarcinoma. Hysterectomy may also be advised, particularly for women who no longer want to have babies. It may reduce the amount of chemotherapy needed. Chemotherapy is given until there are no longer any signs of cancer, based on levels of HCG in the blood. If the initial chemotherapy 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 chemotherapy with a combination of drugs may be needed. Placental-site trophoblastic tumor is treated with hysterectomy. Chemotherapy is usually not helpful. 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 7 or less. Chemotherapy 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 chemotherapy is usually effective. In rare cases, surgical removal of the tumors plus chemotherapy may be used. Blood HCG levels are measured after treatment and should return to normal. 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 8 or higher. Standard treatment is usually an intensive combination chemotherapy regimen such as EMA-CO. Other drug combinations, such as EMA-EP, 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 chemotherapy may be used. Blood HCG levels are measured after treatment and should return to normal. Stage IV gestational trophoblastic tumors These tumors have spread to distant sites such as the liver or brain. Intensive treatment is needed for these tumors. Combination chemotherapy 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 chemotherapy. Again, blood HCG levels are measured after treatment and should return to normal. 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 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. While PSTT has high cure rates, 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 they will likely require more intensive treatment (combination

chemotherapy, sometimes together with radiation and/or surgery).

Will a specialist in gynecologic oncology be involved in my care? Will I be able to have a normal pregnancy later on? How soon after treatment can I get pregnant? What happens after treatment for gestational trophoblastic disease? It may take a while before your confidence in your own recovery begins to feel real and your fears are somewhat relieved. You can learn more about what to look for and how to learn to live with the possibility of cancer coming back in our document,Living With Uncertainty: The Fear of Cancer Recurrence, available at 1-800-227-2345. Follow-up is an important part of the overall treatment plan for gestational trophoblastic disease (GTD). Even after treatment, there is a chance that it could return. This risk 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.

More treatment information For more details on treatment options -- including some that may not be addressed in this document -- the National Cancer Institute (NCI) is a good source of information. The NCI provides treatment guidelines via its telephone information center (1-800-4-CANCER) and its Web site (www.cancer.gov). Detailed guidelines intended for use by cancer care professionals are also available on www.cancer.gov. What should you ask your doctor about gestational trophoblastic disease? It is important to have honest open discussions with your medical team. You should feel free to ask any question, no matter how minor it might seem. Among the questions you might want to ask are: What kind of gestational trophoblastic disease do I have? Has my cancer spread beyond the uterus? Can the stage of my cancer be determined and what does that mean? How much experience do you have treating this type of disease? What treatment choices do I have? Which do you recommend? Why? Does one type of treatment reduce the risk of recurrence more than another? What are the side effects and other risks of each treatment? Based on what you've learned about my cancer, what are my chances of being cured? What should I do to be ready for treatment? How long will it take me to recover from treatment? When can I go back to work after treatment? How soon after treatment can I have sex? Will I need to use birth control? What are the chances that my cancer will come back (recur)? What would we do if this happens?

Follow-up doctor visits 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 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 years 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. 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. For more information, see the section, "How is gestational trophoblastic disease treated?" 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) might be best for you. Most doctors advise against using intrauterine devices (IUDs), as they may increase the risk of bleeding, infection, or puncturing of the uterine wall if tumor is still present.

If you were hospitalized, a copy of the discharge summary that doctors must prepare when patients are sent home. If you received chemotherapy, a list of the drugs and the final doses of each that you received. If you had radiation therapy, a summary of the type and dose of radiation and when and where it was given. It is also important to keep medical insurance. Even though no one wants to think of their cancer coming back, it is always a possibility. If it happens, the last thing you want is to have to worry about paying for treatment. Should your cancer come back our document, When Your Cancer Comes Back: Cancer Recurrence gives you information on how to manage and cope with this phase of your treatment. You can get this document by calling 1-800-227-2345. How about your emotional health? Once your treatment ends, you may find yourself overwhelmed by emotions. This happens to a lot of people. You may have been going through so much during treatment that you could only focus on getting through your treatment. You may find that you think about the potential of your own death, or the effect of your cancer on your family, friends, and career. You may also begin to re-evaluate your relationship with your spouse or partner. Unexpected issues may also cause concern -- for instance, as you become healthier and have fewer doctor visits, you will see your health care team less often. That can be a source of anxiety for some. Getting through treatment for any type of cancer can be a major life stressor, but it may be even more distressing with GTD because it is the result of pregnancy. Patients and their partners have to deal with the loss of a pregnancy at the same time they are faced with treating the tumor. This can be an ideal time to seek out emotional and social support. You need people you can turn to for strength and comfort. Support can come in many forms: family, friends, cancer support groups, church or spiritual groups, online support communities, or individual counselors. Almost everyone who has been through cancer can benefit from getting some type of support. What's best for you depends on your situation and personality. Some people feel safe in peer-support groups or education groups. Others would rather talk in an informal setting such as one-on-one with a trusted friend or counselor. Whatever your source of strength or comfort, make sure you have a place to go with your concerns. The cancer journey can feel very lonely. It is not necessary or realistic to go it all by yourself. And your friends and family may feel shut out if you decide not include them. Let them in -- and let in anyone else who you feel may help. If you aren't

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, there is about a 1% to 2% chance that another molar pregnancy will occur. 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.

Seeing a new doctor Some time after your cancer diagnosis and treatment, you may find yourself in the office of a new doctor. Your original doctor may have moved, or retired, or you may have moved or changed doctors for other reasons. It is important that you are able to give your new doctor the exact details of your diagnosis and treatment. There are certain pieces of information you should have in your possession. These are: A copy of your pathology report from any biopsies or surgeries. If you had surgery, a copy of your operative report. Copies of reports for any imaging tests (ultrasounds, CT scans, etc.) you have had.

sure who can help, call your American Cancer Society at 1800-227-2345 and we can put you in touch with an appropriate group or resource. You can't change the fact that you have had cancer. What you can change is how you live the rest of your life -- making healthy choices and feeling as well as possible, physically and emotionally. 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.

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, ifosfamide, 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. Treatment Option Overview Low Levels of hCG False-positive hCG Pituitary hCG Most hydatidiform moles (HMs) are benign and are treated conservatively by dilation, suction evacuation, and curettage. However, since they carry a risk of persistence or progression to malignant gestational trophoblastic neoplasms (GTNs), they must be followed carefully with weekly serum human chorionic gonadotropin (hCG) levels to normalization. Monthly follow-up for 6 months is generally recommended, although the duration of this phase of follow-up is not based on empiric study. Prompt institution of therapy for GTN and continuing followup at very close intervals until normal beta human chorionic gonadotropin (hCG) titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal hCG titer, depending on the extent of disease. The modified World Health Organization (WHO) Prognostic Scoring System (see Table 4) should be utilized, and combination chemotherapy should be initiated when warranted by the patient's score. If a diagnosis of GTN is made, routine work-up includes the following:

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 that 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.

Serum hCG. Blood work of liver, renal, and marrow function. Chest x-ray. Pelvic ultrasound. Head-computed tomography or magnetic resonance imaging (in the case of choriocarcinoma or central nervous system signs). Treatment of GTN depends on the risk category determined by the Modified WHO Prognostic Scoring System as adapted by the International Federation of Gynecology and Obstetrics (see Table 4). Since the very rare placental-site trophoblastic tumors (PSTTs) and the even more rare epithelioid trophoblastic tumors (ETTs) are biologically distinct entities, their management is discussed separately. Low Levels of hCG Accurate monitoring of hCG is critical to successfully diagnose and monitor the treatment course of gestational trophoblastic disease. False-positive results may lead to inappropriate diagnoses and treatment, and therefore must be minimized. The following are a list of possible alternate diagnoses to be considered in cases of low-level hCG. False-positive hCG Serum hCG testing relies on detecting two antibodies on the hCG molecule. The antibodies are polyclonal or monoclonal antibodies derived from various animals: mouse, rabbit, goat or sheep. Humans with heterophilic (or cross-species) antibodies bind the antibodies in the assay, leading to a falsepositive result. This was a common problem with one of the commercially available assays until it was re-engineered in 2003. Heterophilic antibodies cannot cross the glomerular filtration barrier, so the performance of a urinary hCG can eliminate this source for a positive test result. The urine sample should be run using the same system generally reserved for serum, as opposed to over-the-counter urinepregnancy tests, to avoid decreased sensitivity in the latter. Pituitary hCG The anterior stalk of the pituitary secretes luteinizing hormone (LH), which shares an alpha subunit with hCG. In normal menstrual cycles, pituitary generated hCG may be detectable at the time of the LH surge. Estrogen provides negative feedback for this LH secretion and acts as a suppressing agent. In patients in low-estrogen states (perimenopause, menopause, and status postoophorectomy) pituitary hCG may be secreted in increasing amounts, although only levels between 1 to 32 mIU/mL have been recorded.[1] To confirm a pituitary source for the hCG, patients are started on high-dose oral contraceptive pills to produce an exogenous source of estrogen. In general,

patients with pituitary hCG will have their hCG levels suppressed after 3 weeks on this regimen.[1] References 1. Muller CY, Cole LA: The quagmire of hCG and hCG testing in gynecologic oncology. Gynecol Oncol 112 (3): 663-72, 2009. [PUBMED Abstract]

http://www.cancer.gov/cancertopics/pdq/treatment/gestati onaltrophoblastic/HealthProfessional/page4 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:[1] 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 cystlike 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.[1,2] 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. Epithelioid trophoblastic tumor Epithelioid trophoblastic tumor is an extremely rare gestational trophoblastic tumor.[4,5] Although originally termed atypical choriocarcinoma, it appears to be less aggressive than choriocarcinoma and is now regarded as a distinct entity. Pathologically, it has a monomorphic cellular pattern of epithelioid cells and may resemble squamous cell cancer of the cervix when arising in the cervical canal. Its clinical behavior appears to be closer to that of PSTT than to choriocarcinoma. It has a spectrum of clinical behavior from benign to malignant. About one-third of patients present with metastases, usually in the lungs. Low-Risk Gestational Trophoblastic Neoplasia (FIGO Score 06) Treatment Current Clinical Trials There is no consensus on the best chemotherapy regimen for initial management of low-risk gestational trophoblastic neoplasia (GTN), and first-line regimens vary by geography and institutional preference. Most regimens have not been compared head-to-head, and the level of evidence for efficacy is therefore often limited to 3iiDii except as noted below. Importantly, even if there are differences in initial remission rate among the regimens, salvage with alternate regimens is very effective, and the ultimate cure rates are generally 99% or more. The initial regimen is generally given until a normal hCG (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the hCG). A salvage regimen is instituted if any of the following occur: A plateau of the hCG for 3 weeks (defined as a hCG decrease of 10% or less for 3 consecutive weeks). A rise in hCG of greater than 20% for 2 consecutive weeks. Metastases appear. The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration

systematic review.[1] In that systematic review, four randomized controlled trials were identified.[2-5] Three of the randomized trials [3-5] compared the same two commonly used regimens: Biweekly (pulsed) intravenous dactinomycin (1.25 mg/m ). Weekly intramuscular methotrexate (30 mg/m ). These three trials included a total of 392 patients. All three trials showed better primary complete response (CR) rates without the need for additional salvage therapy associated with pulsed dactinomycin (Relative Risk [RR] of cure = 3.00; 95% CI, 1.108.17), even though the magnitude of benefit 2 showed substantial heterogeneity (I statistic = 79%).[35][Level of evidence: 1iiDii] Fewer courses of therapy were needed to achieve CR and cure with dactinomycin treatment as well. As expected, salvage chemotherapy was nearly uniformly successful, since almost all low-risk GTN patients are ultimately cured, irrespective of the initial chemotherapeutic regimen. There were no statistically significant differences in most toxicities, including the following: Nausea and vomiting. Diarrhea. Hematologic toxicity. Hepatic toxicity. There was a statistically significant increase in dermatologic toxicity, including alopecia, associated with dactinomycin. However, in the largest study,[5] there was statistically significantly more low-grade gastrointestinal toxicity, grade 2 nausea, grade 1 to 2 vomiting, and grades 1 to 3 neutropenia in the dactinomycin group. In that study, choriocarcinoma patients and patients with a risk score of 5 to 6 had a worse CR rate to initial treatment with single-agent therapy, and methotrexate was virtually ineffective.[5] The fourth randomized trial was a very small study of 45 patients, comparing a 5-day regimen of dactinomycin (10 g/kg) to an 8-day regimen of methotrexate (1 mg/kg) and folinic acid (0.1 mg/kg) on alternate days. There was a statistically significant decrease in risk of failure to achieve primary cure without the need for salvage therapy in the dactinomycin arm (RR = 0.57; 95% CI, 0.400.81).[2][Level of evidence: 1iiDii] There was less alopecia associated with methotrexate but more hepatic toxicity. The Cochrane systematic review also summarized the evidence from four nonrandomized trials, but comparisons across studies are difficult. The regimens evaluated in those studies are included in the lists below.[1][Level of evidence: 3iiDii] Commonly used treatment regimens include the following:
2 2

1.

2. 3.

The 8-day Charing Cross regimen. Methotrexate (50 mg intramuscularly (IM) on days 1, 3, 5, and 7) and folinic acid (7.5 mg orally on days 2, 4, 6, and 8). This may be the most common regimen worldwide,[1,6] but it has not been directly compared to other regimens. 2 Biweekly pulsed dactinomycin (1.25 mg/m IV). 2 Weekly methotrexate (30 mg/m IM). Efficacy of this regimen appears to be low for choriocarcinoma and for patients with Fderation Internationale de Gyncologie et dObsttrique (FIGO) risk scores of 5 6.

Other regimens in less-common use include the following:[1] An 8-day regimen of methotrexate (1 mg/kg IM days 1, 3, 5, and 7) and folinic acid (0.1 mg/kg IM days 2, 4, 6, and 8). Methotrexate 20 mg/m IM days 15, repeated every 14 days. Dactinomycin 12 g/kg/day IV days 15, repeated every 23 weeks. This regimen has fallen out of favor because of substantial alopecia and nausea. Methotrexate 20 mg IM daily, days 15; and dactinomycin 500 g IV daily, days 15, repeated every 14 days. Dactinomycin 10 g/kg/day, days 15, repeated every 2 weeks. Methotrexate 0.4 mg/kg/day IM daily on days 15, repeated after 7 days. Etoposide 100 mg/m /day IV on days 15, or 250 mg/m IV on days 1 and 3, at 10-day intervals.[7] The unusual patient with a tumor that becomes refractory to single-agent chemotherapy is treated with one of the combination regimens described below for high-risk GTN. (Refer to the High-Risk Gestational Trophoblastic Neoplasia (FIGO Score 7) Treatment section of this summary for more information.) Current Clinical Trials Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withlow risk metastatic gestational trophoblastic tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria. General information about clinical trials is also available from the NCI Web site. http://www.cancer.gov/cancertopics/pdq/treatment/gestati onaltrophoblastic/HealthProfessional/page6
2 2 2

cancer.

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Gonzalez Related Regimen (PDQ) Pages [ patient ] [ health professional ] Complementary and Alternative Medicine in Cancer Treatment (PDQ) Expert-reviewed information summary ab [ patient ] Levels of(PDQ) Evidence for Expert-reviewed information summary about the use of complementary and Hydrazine Sulfate Human Studies of Cancer alternative medicine as a treatment for people with cancer. [ patient ] [ health professional ] Complementary and Expert-reviewed information summary ab cancer. Alternative Medicine Specific Topics (PDQ) [ health professional ] Laetrile/Amygdalin (PDQ) 714-X (PDQ) Information about how [ patient ] [ health professional ] to [ patient ] [ health professional ] weigh the strength of the Expert-reviewed information summary ab Expert-reviewed information summary about the use of 714-X as a evidence obtained in cancer. treatment for people with cancer. human studies of complementary and Milk Thistle (PDQ) Acupuncture (PDQ) alternative medicine [ patient ] [ health professionalfor ] [ patient ] [ health professional ] cancer. information summary ab Expert-reviewed Expert-reviewed information summary about acupuncture as a treatment for people with cancer or cancer-related disorders. - NCI's MistletoePDQ Extracts (PDQ) Comprehensive Cancer [ patient ] [ health professional ] Antineoplastons (PDQ) Database Expert-reviewed information summary ab [ patient ] [ health professional ] cancer. Expert-reviewed information summary about antineoplastons as a PDQ Cancer CAM treatment for people with cancer. Editorial Newcastle DiseaseBoard Virus (PDQ) [ patient ] [ health professional ] Aromatherapy and Essential Oils (PDQ) Expert-reviewed information summary ab [ patient ] [ health professional ] with cancer. Expert-reviewed information summary about the use of aromatherapy people and essential oils to improve the quality of life of cancer patients. PC-SPES (PDQ) [ patient ] [ health professional ] Cancell/Cantron/Protocel (PDQ) Expert-reviewed information summary ab [ patient ] [ health professional ] Expert-reviewed information summary about the use of Cancell/Entelev as a treatment for people with Selected Vegetables/Sun's Soup (PDQ) cancer. [ patient ] [ health professional ] Expert-reviewed information summary ab Cannabis and Cannabinoids (PDQ) people with cancer. [ health professional ] Expert-reviewed information summary about the use of Cannabis and cannabinoids in the treatment of Spirituality in Cancer Care (PDQ) cancer-related side effects, such as nausea and vomiting. [ patient ] [ health professional ] Expert-reviewed information summary ab Cartilage (Bovine and Shark) (PDQ) have cancer. Various approaches for man [ patient ] [ health professional ] Expert-reviewed information summary about the use of bovine and shark cartilage as a treatment for people with cancer. Coenzyme Q10 (PDQ) Spirituality in cancer care [ patient ] [ health professional ] Expert-reviewed information summary about the use of coenzyme Q10 as a treatment for people with Overview cancer. Essiac/Flor Essence (PDQ) National surveys consistently support the idea that religion [ patient ] [ health professional ] and spirituality important to most individuals in the Expert-reviewed information summary about the use of are Essiac/Flor Essence as a treatment for people with

general population. More than 90% of adults express a belief in God, and slightly more than 70% of individuals surveyed identified religion as one of the most important influences in their lives.[1] Yet even widely held beliefs, such as survival of the soul after death or a belief in miracles, vary substantially by gender, education, and ethnicity.[2] Research indicates that both patients and family caregivers [3,4] commonly rely on spirituality and religion to help them deal with serious physical illnesses, expressing a desire to have specific spiritual and religious needs and concerns acknowledged or addressed by medical staff; these needs, although widespread, may take different forms between and within cultural and religious traditions.[5-7] A survey of hospital inpatients found that 77% of patients reported that physicians should take patients' spiritual needs into consideration, and 37% wanted physicians to address religious beliefs more frequently.[8] A large survey of cancer outpatients in New York City found that a slight majority felt it was appropriate for a physician to inquire about their religious beliefs and spiritual needs, although only 1% reported that this had occurred. Those who reported that spiritual needs were not being met gave lower ratings to quality of care (P < .01) and reported lower satisfaction with care (P < .01).[7] A pilot study of 14 African American men with a history of prostate cancer found that most had discussed spirituality and religious beliefs with their physicians; they expressed a desire for their doctors and clergy to be in contact with each other.[9] Sixty-one percent of 57 inpatients with advanced cancer receiving end-of-life care in a hospital supported by the Catholic archdiocese reported spiritual distress when interviewed by hospital chaplains. Intensity of spiritual distress correlated with self-reports of depression but not with physical pain or with perceived severity of illness.[10] Another study [11] of advanced cancer patients (N = 230) in New England and Texas assessed their spiritual needs. Almost half (47%) reported that their spiritual needs were not being met by a religious community, and 72% reported that these needs were not supported by the medical system. When such support existed, it was positively related to improved quality of life. Furthermore, having spiritual issues addressed by the medical care team had more impact on increasing the use of hospice and decreasing aggressive end-of-life measures than did pastoral counseling.[12] This summary will review the following topics: How religion and spirituality can be usefully conceptualized within the medical setting. The empirical evidence for the importance of religious and spiritual factors in adjustment to illness in general and to cancer in particular, throughout the course of illness and at the end of life, for both patients and family caregivers.[3]

The range of assessment approaches that may be useful in a clinical environment. Various models for management and intervention. Resources for clinical care. Paying attention to the religious or spiritual beliefs of seriously ill patients has a long tradition within inpatient medical environments. Addressing such issues has been viewed as the domain of hospital chaplains or a patients own religious leader. In this context, systematic assessment has usually been limited to identifying a patients religious preference; responsibility for management of apparent spiritual distress has been focused on referring patients to the chaplain service.[13-15] Although health care providers may address such concerns themselves, they are generally very ambivalent about doing so,[16] and there has been relatively little systematic investigation addressing the physicians role. These issues, however, are being increasingly addressed in medical training.[17] Acknowledging the role of all health care professionals in spirituality, a multidisciplinary group from one cancer center developed a four-stage model that allows health care professionals to deliver spiritual care consistent with their knowledge, skills, and actions at one of four skill levels.[18] Interest in and recognition of the function of religious and spiritual coping in adjustment to serious illness, including cancer, has been growing.[19-23] New ways to assess and address religious and spiritual concerns as part of overall quality of life are being developed and tested. Limited data support the possibility that spiritual coping is one of the most powerful means by which patients draw on their own resources to deal with a serious illness such as cancer; however, patients and their family-member caregivers may be reluctant to raise religious and spiritual concerns with their professional health care providers.[24-26] Increased spiritual well-being in a seriously ill population may be linked with lower anxiety about death,[27] but greater religious involvement may also be linked to an increased likelihood of desire for extreme measures at the end of life.[28] Given the importance of religion and spirituality to patients, integrating systematic assessment of such needs into medical care, including outpatient care, is crucial. The development of better assessment tools will make it easier to discern which aspects of religious and spiritual coping may be important in a particular patient's adjustment to illness. Of equal importance is the consideration of how and when to address religion and spirituality with patients and the best ways to do so in different medical environments.[29-31] Although addressing spiritual concerns is often considered an end-of-life issue, such concerns may arise at any time after diagnosis.[24] Acknowledging the importance of these concerns and addressing them, even briefly, at diagnosis may facilitate better adjustment throughout the course of treatment and create a context for richer dialogue later in the illness. One study of 118 patients seen in follow-up by one of

four oncologists suggests that a semistructured inquiry into spiritual concerns related to coping with cancer is well accepted by patients and oncologists and is associated with positive perceptions of care and well-being.[32] In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading. 1.

religious engagement.

From the prospective of both the research and clinical literature spirituality, and health, it is important to consider how these con investigators and authors. Much of the epidemiological literature religion and health has been based on definitions of religious inv religious group or frequency of church attendance. Somewhat m religious practices such as belief in God, frequency of prayer, or r engage in such practices or believe in God without necessarily at carries certain connotations; the term religiosity, for example, ha undue investment in particular religious practices or beliefs. Relig refer to the dimension of religious practice.

Spirituality and spiritual well-being are more challenging to defin profound mystical experiences; however, in considerations of eff http://www.cancer.gov/cancertopics/pdq/supportivecare/spi more helpful definitions focus on accessible feelings, such as a se rituality/HealthProfessional purpose in life, or awe when walking in nature. For the purposes continuum of meaningful spiritual experiences, from the commo transformative. Both type and intensity of experience may vary. identified by those working with medical patients include a sense Definitions sense of connectedness to others or to God. Low levels of these coping (refer to the Relation of Religion and Spirituality to Adjust Specific religious beliefs and practices should be distinguished from theIndices idea ofsection).[3] a universal capacity for spiritual

and religious experiences. Although this distinction may not be salient or important on a personal basis, it is The definition ofdifferent acute spiritual distress must be considered sepa important conceptually for understanding various aspects of evaluation and the role of beliefs, belief that cancer reflects punishment by God or may accompany practices, and experiences in coping with cancer. A cancer patient may also suffer a loss of faith.[8] Although many time following diagnosis, only is a few individuals become obsessed The most useful general distinction to make in this context is between religion and spirituality. There no general measure of religious and spiritual distress agreement on definitions of either term, but there is general agreement on the usefulness of this distinction. A (such as the Negative s CopeNegative]).[8] High levels of spiritual distress may contribu number of reviews address matters of definition.[1-3] Religion can be viewed as a specific set of beliefs and outcomes.[9,10] The tools for measuring these dimensions are d practices associated with a recognized religion or denomination. Spirituality is generally recognized as Spiritual Concerns section. encompassing experiential aspects, whether related to engaging in religious practices or to acknowledging a

general sense of peace and connectedness. The concept of spirituality is found in all cultures and is often References considered to encompass a search for ultimate meaning through religion or other paths.[4] Within health care, concerns about spiritual or religious well-being have sometimes been viewed as an aspect of complementary and Halstead than MT, Mickley JR: Attempting to fathom the unfa alternative medicine (CAM), but this perception may be more characteristic1. of providers of patients. In one Semin Nurs 13 (4): 225-30, 1997. [PUBMED Abstr study,[5] virtually no patients but about 20% of providers said that CAM services were Oncol sought to assist with spiritual or religious issues. Religion is highly culturally determined; spirituality is considered a universal human 2. Zinnbauer BJ, Pargament KL: Spiritual conversion: a stud capacity, usuallybut not necessarilyassociated with and expressed in religious practice. Most individuals Study Relig 37(1): 161-180, 1998. consider themselves both spiritual and religious; some may consider themselvesSci religious but not spiritual. Others, including some atheists (people who do not believe in the existence of God) or agnostics (people who 3. but Breitbart W, Gibson Poppito believe that God cannot be shown to exist), may consider themselves spiritual not religious. In a C, sample of SR, et al.: Psychotherape meaning and spirituality. Can J Psychiatry 49 (6): 366-72 369 representative cancer outpatients in New York City (33% minority), while only 6% identified themselves as agnostic or atheist, only 29% attended religious services weekly; 66% represented themselves as spiritual but not 4. Task force report: spirituality, cultural issues, and end of religious.[6] Colleges.: Report III. Contemporary Issues in Medicine: C Association of American Medical Colleges, 1999, pp 24-9 One effort to characterize individuals by types of spiritual and religious experience [7] identified the following three groups, using cluster analytic techniques: 5.

Ben-Arye E, Bar-Sela G, Frenkel M, et al.: Is a biopsychos treatment? A study of patients and oncology staff memb 1. Religious individuals who highly value religious faith, spiritual well-being, and the meaning of life. spirituality. Support Care Cancer 14 (2): 147-52, 2006. [ 2. Existential individuals who highly value spiritual well-being but not religious faith. 3. Nonspiritual individuals who have little value for religiousness, spirituality, or a sense of the meaning of 6. Astrow AB, Wexler A, Texeira K, et al.: Is failure to meet life. perceptions of quality of care and their satisfaction with 2007. [PUBMED Abstract] Individuals in the third group were far more distressed about their illness and were experiencing worse adjustment. There is as yet no consensus on the number or types of underlying of spirituality oret al.: Types of spiritual well7. dimensions Riley BB, Perna R, Tate DG,

relation to various forms of quality of life. Arch Phys Me

(P < .0001). There was also a negative correlation between the existential well-being scores and the anxiety and 8. Pargament KI: The Psychology of Religion and Coping: Theory, Research, Practice. York, NY: Guilford depression scores but not New with the religious well-being score Press, 1997. (P < .001).[15] These patterns were also found in a large study of indigent prostate cancer survivors; the patterns were 9. Pargament KI, Koenig HG, Tarakeshwar N, et al.: Religious struggle across as a predictor of mortality among consistent ethnicity and metastatic status.[16] medically ill elderly patients: a 2-year longitudinal study. Arch Intern Med 161 (15): 1881-5, 2001 Aug 1327. [PUBMED Abstract] In a large (N = 418) study of breast cancer patients, a higher level of meaning and peace was associated with a decline in 10. Hills J, Paice JA, Cameron JR, et al.: Spirituality and distress in palliative consultation. J Palliat Med 8 depression overcare 12 months, whereas higher religiousness (4): 782-8, 2005. [PUBMED Abstract] predicted an increase in depression, particularly if meaning/peace was lower.[17][Level of evidence: II] A second Relation of Religion and Spirituality to Adjustment, Quality study with mixed gender/mixed cancer survivors (N = 165) of Life, and Health Indices found similar patterns. In both studies, high levels of religiousness were linked to increases in perceived cancerrelated growth.[17][Level of evidence: II] In a convenience sample, 222 low-income men with prostate cancer were Religion and spirituality have been shown to be significantly surveyed about spirituality and health-related quality of life. associated with measures of adjustment and with the Low scores in spirituality, as measured by the peace/meaning management of symptoms in cancer patients. Religious and and faith subscale of the Functional Assessment of Chronic spiritual coping have been associated with lower levels of Illness TherapySpiritual Well-Being (FACIT-Sp), were patient discomfort as well as reduced hostility, anxiety, and associated with significantly worse physical and mental social isolation in cancer patients [1-4] and in family health than were high scores in spirituality.[18] caregivers.[5] Specific characteristics of strong religious beliefs, including hope, optimism, freedom from regret, and life satisfaction, have also been associated with improved A large national survey study of female family caregivers (N = adjustment in individuals diagnosed with cancer.[6,7] 252; 89% white) identified that higher levels of spirituality, as measured by the FACIT-Sp, were associated with much less psychological distress (measured by the Pearlin Stress Scale). Type of religious coping may influence quality of life. In a Participants with higher levels of spirituality actually had multi-institutional cross-sectional study of 170 patients with improved well-being even as caregiving stress increased, advanced cancer, more use of positive religious coping while those with lower levels of spirituality showed the methods (such as benevolent religious appraisals) was opposite pattern, suggesting a strong stress-buffering effect associated with better overall quality of life and higher scores of spiritual well-being. This finding reinforces the need to on the existential and support domains of the McGill Quality identify low spiritual well-being when assessing the coping of Life Questionnaire. In contrast, more use of negative capacity of family caregivers as well as patients.[5] religious coping methods (such as anger at God) was related to poorer overall quality of life and lower scores on the existential and psychological domains.[8,9] A study of 95 One author [19] found that cancer survivors who had drawn cancer patients diagnosed within the past 5 years found that on spiritual resources reported substantial personal growth spirituality was associated with less distress and better as a function of dealing with the trauma of cancer. This was quality of life regardless of perceived life threat, with also found in a survey study of 100 well-educated, mostly existential well-being but not religious well-being as the married/partnered white women with early-stage breast major contributor.[10] cancer, recruited for the study from an Internet Web site, in which increasing levels of spiritual struggle were related to poorer emotional adjustment, though not to other aspects of Spiritual well-being, particularly a sense of meaning and cancer-related quality of life.[20] Using path analytic peace,[11] is significantly associated with an ability of cancer techniques, a study of women with breast cancer found that patients to continue to enjoy life despite high levels of pain or at both prediagnosis and 6 months postsurgery, holding fatigue. Spiritual well-being and depression are inversely negative images of God was the strongest predictor of related.[12,13] Higher levels of a sense of inner meaning and emotional distress and lower social well-being.[21] However, peace have also been associated with lower levels of longitudinal analyses failed to find sustained effects for depression, whereas measures of religiousness were baseline positive or negative attitudes toward God at either 6 unrelated to depression.[14] or 12 months. One possible explanation for these findings is that such attitudes are somewhat unstable during a period of This relationship has been specifically demonstrated in the uncertainty (e.g., at prediagnosis).[21] cancer setting. In a cross-sectional survey of 85 hospice patients with cancer, there was a negative correlation between anxiety and depression (as measured by the Hospital Anxiety and Depression Scale) and overall spiritual well-being (as measured by the Spiritual Well-Being Scale) Engaging in prayer is often cited as an adaptive tool,[22] but qualitative research [23] found that for about one third of cancer patients interviewed, concerns about how to pray

Abstract]

effectively or the questions raised about the effectiveness of prayer also caused inner conflict and mild distress. A useful discussion of how prayer is used by cancer patients and how clinicians might conceptualize prayer has been published.[24] Ethnicity and spirituality were investigated in a qualitative study of 161 breast cancer survivors. In individual interviews, most participants (83%) spoke about some aspect of their spirituality. Seven themes were identified: God as a Comforting Presence, Questioning Faith, Anger at God, Spiritual Transformation of Self and Attitude Towards Others/Recognition of Own Mortality, Deepening of Faith, Acceptance, and Prayer by Self. A higher percentage of African Americans, Latinas, and persons identified as Christians were more likely to feel comforted by God than were other groups.[25] Positive religious involvement and spirituality appear to be associated with better health and longer life expectancy, even after controlling for other variables such as health behaviors and social support, as shown in one metaanalysis.[26] Although little of this research is specific to cancer patients, one study of 230 patients with advanced cancer (expected prognosis <1 year) investigated a variety of associations between religiousness and spiritual support.[27] Most study participants (88%) considered religion either very important (68%) or somewhat important (20%); more African Americans and Hispanics than whites reported religion to be very important. Spiritual support by religious communities or the medical system was associated with better patient quality of life. Age was not associated with religiousness. At the time of recruitment to participate in the study, increasing selfreported distress was associated with increasing religiousness, and private religious or spiritual activities were performed by a larger percentage of patients after their diagnosis (61%) than before (47%). Regarding spiritual support, 38% reported that their spiritual needs were supported by a religious community to a large extent or completely, while 47% reported receiving support from a religious community to a small extent or not at all. Finally, religiousness was also associated with the end-of-life treatment preference of wanting all measures taken to extend life. Another study *28] found that helper and cytotoxic T-cell counts were higher among women with metastatic breast cancer who reported greater importance of spirituality. Other investigators [29] found that attendance at religious services was associated with better immune system functioning. Other research [30,31] suggests that religious distress negatively affects health status. These associations, however, have been criticized as weak and inconsistent.[32] Several randomized trials with cancer patients have suggested that group support interventions benefit survival.[33,34] These studies must be interpreted cautiously, however. First, the treatments focused on general psychotherapeutic issues and psychosocial support. Although spiritually relevant issues undoubtedly arose in these

settings, they were not the focus of the groups. Second, there has been difficulty replicating these effects.[35] References 1. Acklin MW, Brown EC, Mauger PA: The role of religious values in coping with cancer. J Relig Health 22 (4): 322-333, 1983. Kaczorowski JM: Spiritual well-being and anxiety in adults diagnosed with cancer. Hosp J 5 (3-4): 105-16, 1989. [PUBMED Abstract] Koenig HG, Cohen HJ, George LK, et al.: Attendance at religious services, interleukin-6, and other biological parameters of immune function in older adults. Int J Psychiatry Med 27 (3): 233-50, 1997. [PUBMED Abstract] Koenig HG, Pargament KI, Nielsen J: Religious coping and health status in medically ill hospitalized older adults. J Nerv Ment Dis 186 (9): 513-21, 1998. [PUBMED Abstract] Pargament KI, Koenig HG, Tarakeshwar N, et al.: Religious struggle as a predictor of mortality among medically ill elderly patients: a 2-year longitudinal study. Arch Intern Med 161 (15): 1881-5, 2001 Aug 13-27. [PUBMED Abstract] Sloan RP, Bagiella E: Claims about religious involvement and health outcomes. Ann Behav Med 24 (1): 14-21, 2002 Winter. [PUBMED Abstract] Spiegel D, Bloom JR, Kraemer H, et al.: Psychological support for cancer patients. Lancet 2 (8677): 1447, 1989. [PUBMED Abstract] Fawzy FI, Fawzy NW, Hyun CS, et al.: Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 50 (9): 681-9, 1993. [PUBMED Abstract] Cunningham AJ, Edmonds CV, Jenkins GP, et al.: A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psychooncology 7 (6): 50817, 1998 Nov-Dec. [PUBMED Abstract]

2.

3.

4.

5.

6.

7.

8.

9.

Screening and Assessment of Spiritual Concerns Standardized Assessment Measures Interviewing Tools Raising spiritual concerns with patients can be accomplished by the following approaches:[1,2]

Waiting for the patient to bring up spiritual concerns. Requesting that the patient complete a paper-and-pencil assessment. Having the physician do a spiritual inquiry or assessment by indicating his or her openness to a discussion. These approaches have different potential value and limitations. Patients may express reluctance to bring up spiritual issues, noting that they would prefer to wait for the provider to broach the subject. Standardized assessment tools vary, have generally been designed for research purposes, and need to be reviewed and utilized appropriately by the provider. Physicians, unless trained specifically to address such issues, may feel uncomfortable raising spiritual concerns with patients.[3] However, an increasing number of models are becoming available for physician use and training.[4] Numerous assessment tools are pertinent to performing a religious and spiritual assessment. Table 1summarizes a selection of assessment tools. Several factors should be considered before choosing an assessment tool:

between religion or spirituality, health indices, and adjustment to illness. Duke Religious Index (DRI). The DRI (or DUREL) [5][Level of evidence: II][6] is short (five items) and has reasonable psychometric properties [5] examined in cancer patients. It is best used as an indicator of religious involvement rather than spirituality and has low or modest correlations with psychological well-being. Systems of Belief Inventory (SBI-15R). The SBI-15R [7][Level of evidence: II] has undergone careful psychometric development and measures two domains: 1. 2. Presence and importance of religious and spiritual beliefs and practices. Value of support from a religious/spiritual community.

The questions are worded well and may provide a good initiation for further discussion and exploration. Brief Measure of Religious Coping (RCOPE). The Brief RCOPE [8][Level of evidence: II] has two dimensions: positive religious coping and negative religious coping, with five items each. The second factor appears to uniquely identify a very important aspect of spiritual adjustment, i.e., the degree to which conflict, self-blame, or anger at God is present for an individual. A longer form of the scale, with additional dimensions, would be suitable for a more comprehensive assessment of religious/spiritual concerns. Psychometric development is high. While high scores in negative religious coping are unusual, they are particularly powerful in predicting poor adjustment to disease.[9] Functional Assessment of Chronic Illness TherapySpiritual Well-Being (FACIT-Sp).[10] The FACIT-Sp is part of the widely used Functional Assessment of Cancer Therapy (FACT) quality-of-life battery.[11] It was developed with an ethnically diverse cancer population and contains 12 items and 2 factors (faith, and meaning and peace), with good to excellent psychometric properties; although some evidence suggests that inner meaning and inner peace can be identified as two separate factors, such identification does not appear to substantially improve associations with other indicators of well-being.[12] One characteristic of this scale is that the wording of items does not assume a belief in God. Therefore, it can be comfortably completed by an atheist or agnostic, yet it taps into both traditional religiousness dimensions (faith factor) and spiritual dimensions (meaning and peace factor). The meaning and peace factor has been shown to have particularly strong associations with psychological adjustment, in that individuals who score high on this scale are much more likely to report generally enjoying life despite fatigue or pain, are less likely to desire a hastened death at the end of life,[13][Level of evidence: II] report better disease-specific and psychosocial adjustment,[14-16] and report lower levels of helplessness/hopelessness.[16] These associations have been shown to be independent of other indicators of

Focus of the evaluation (religious practice or spiritual wellbeing/distress). Purpose of the assessment (e.g., screening for distress vs. evaluation of all patients as part of care). Modality of the assessment (interview or questionnaire). Feasibility of the assessment (staff and patient burden). The line between assessment and intervention is blurred, and simply inquiring about an area such as religious or spiritual coping may be experienced by the patient as an opening for further exploration and validation of the importance of this experience. Evidence suggests that such an inquiry will be experienced as intrusive and distressing by only a very small proportion of patients. Key assessment approaches are briefly reviewed below; pertinent characteristics are summarized in Table 1. Standardized Assessment Measures One of several paper-and-pencil measures can be given to patients to assess religious and spiritual needs. These measures have the advantage of being self-administered; however, they were mostly designed as research tools, and their role for clinical assessment purposes is not as well understood. These measures may be helpful in opening up the area for exploration and for ascertaining basic levels of religious engagement or spiritual well-being (or spiritual distress). Most also assume a belief in God and therefore may seem inappropriate for an atheist or agnostic patient, who may still be spiritually oriented. All of the measures have undergone varying degrees of psychometric development, and most are being used in investigations of the relationship

adjustment, supporting the value of adding assessment of this dimension to standard quality-of-life evaluations.[10,16] Total scores on the FACIT-Sp correlated highly over time (27 weeks) with a 10-point linear analogue scale of spiritual wellbeing in a sample of advanced cancer patients. The linear scale (Spiritual Well-Being Linear Analogue Self-Assessment [SWB LASA]) was worded, How would you describe your overall spiritual well-being? and ratings ranged from 0 (as bad as it can be) to 10 (as good as it can be).[17] Spiritual Transformation Scale (STS).[18] The STS is a 40item measure of change in spiritual engagement following cancer diagnosis. It has two subscales: Spiritual Growth (SG) and Spiritual Decline (SD). The SG factor is highly correlated with the Positive RCOPE = .71) and the Post-traumatic Growth Inventory = .68), while the SD factor is correlated with the Negative RCOPE = .56) and the Center for Epidemiologic Studies Depression Scale (CES-D) = .40). Analyses show that the STS accounts for additional variance on depression, other measures of adjustment (Positive and Negative Affect Schedule [PANAS]), and the Daily Spiritual Experience Scale.[18] Individuals with later stage cancer (stage III or IV) had higher scores on SG, as did individuals with a recurrence rather than a new diagnosis. Individuals with higher scores on SD were more likely to have not graduated from high school. A unique strength of this scale is that it is specific to change in spirituality since diagnosis; wording on items is also generally appropriate for individuals who identify as spiritual rather than religious. Among the limitations of this scale is that development to date includes mostly observant Christians, with few minorities in the sample. Interviewing Tools The following are semistructured interviewing tools designed to facilitate an exploration, by the physician or other health care provider, of religious beliefs and spiritual experiences or issues. The tools take the spiritual history approach and have the advantage of engaging the patient in dialogue, identifying possible areas of concern, and indicating the need for provision of further resources such as referral to a chaplain or support group. These approaches, however, have not been systematically investigated as empirical measures or indices of religiousness or of spiritual well-being or distress. The SPIRITual History.[19] The SPIRIT is an acronym for the six domains explored by this tool: S, spiritual belief system; P, personal spirituality; I, integration with a spiritual community; R, ritualized practices and restrictions; I, implications for medical care; T, terminal events planning. The 6 domains are covered by 22 items, which may be covered in as little as 10 or 15 minutes or integrated into general interviewing over several appointments. A strength of this tool is the number of questions pertinent to managing serious illness and to gaining an understanding of how patient religious beliefs may bear on patient care decisions.

Faith, Importance/Influence, Community, and Address (FICA) Spiritual History.[1] FICA is an acronym for Faith, Importance/Influence, Community, and Address, with a set of questions to explore each area (e.g., What is your faith? How important is it? Are you part of a religious community? How would you like me as your provider to address these issues in your care?). Although developed as a spiritual history tool for use in primary care settings, it would lend itself to any patient population. The relative simplicity of the approach has led to its adoption by many medical schools. Table 1. Assessment of Religion and Spirituality in Cancer Patients Enlarge Purpose/ Focus/ Subscale (No.) Speci fic to Canc er Patie nts? Yes Level of Psycho metric Develo pment High Length/ Other Characte ristics/ Commen ts Four items assume belief in God

Tool

Devel oper

Systems of Belief Inventory (SBI-15R) [7]

Hollan Two d et factors: al. Beliefs/ex perience (10); religious social support (5) Religious involveme nt (5) Two factors: Meaning & peace (8), faith (4) Two factors: Positive coping; negative coping/dis tress Multiple subscales

DRI/DURE Sher L [5] man et al. FACIT-Sp [10,15] Brady et al.; Peter man

Yes

Modera te High. Limited crossvalidati on data. Very High Part of FACT-G qualityof-life battery [11]

Yes

Brief RCOPE [8]

Parga ment et al.

No

Fetzer Multidim ensional Scale [20] FICA: Spiritual history [1]

Fetzer

No

High. Under develop ment. Low MD intervie w assessm ent

Pucha lski et al.

Brief spiritual history

No

Tool

Devel oper

Purpose/ Focus/ Subscale (No.) In-depth interview with guided questions Two factors: Spiritual Growth and Spiritual Decline

Speci fic to Canc er Patie nts? No

Level of Psycho metric Develo pment Low

Length/ Other Characte ristics/ Commen ts MD intervie w assessm ent Forty items. Unique to assessing change in spiritual experien ce post cancer diagnosis .

Exploration by the physician or other health care provider within the context of usual medical care. Encouragement for the patient to seek assistance from his or her own clergy. Formal referral to a hospital chaplain. Referral to a religious or faith-based therapist. Referral to a range of support groups that are known to address spiritual issues. Two survey studies [1,2] found that physicians consistently underestimate the degree to which patients want spiritual concerns addressed. An Isreali study found that patients expressed the desire that 18% of a hypothetical 10-minute visit be spent addressing such concerns, while their providers estimated that 12% of the time should be spent in this way.[2] This study also found that while providers perceived that a patient's desire for addressing spiritual concerns related to a broader interest in complementary and alternative medicine (CAM) modalities, patients viewed CAMrelated issues and spiritual/religious concerns as quite separate. Physicians A task force [3] of physicians and end-of-life specialists suggested several guidelines for physicians who wish to respond to patients spiritual concerns:

SPIRIT [19]

Maug ans

Spiritual Transfor mation Scale (STS) [18]

Cole et al.

Yes

Modera te

References 1. Cole BS, Hopkins CM, Tisak J, et al.: Assessing spiritual growth and spiritual decline following a diagnosis of cancer: reliability and validity of the spiritual transformation scale. Psychooncology 17 (2): 112-21, 2008. [PUBMED Abstract] Maugans TA: The SPIRITual history. Arch Fam Med 5 (1): 11-6, 1996. [PUBMED Abstract] Multidimensional Measurement of Religiousness/Spirituality for Use in Health Research: A Report of the Fetzer Institute/National Institute on Aging Working Group. Kalamazoo, Mich: Fetzer Institute, 1999.

Respect the patients views and follow the patients lead. Make a connection by listening carefully and acknowledging the patients concerns, but avoid theological discussions or engaging in specific religious rituals. Maintain one's own integrity in relation to one's own religious beliefs and practices. Identify common goals for care and medical decisions. Mobilize other resources of support for the patient, such as referring the patient to a chaplain or encouraging contact with the patients own clergy. Inquiring about religious or spiritual concerns by physicians or other health care professionals may provide valuable and appreciated support to patients. Most cancer patients appear to welcome a dialogue about such concerns, regardless of diagnosis or prognosis. In a large survey of cancer outpatients, between 20% and 35% expressed a desire for religious and spiritual resources, help with talking about finding meaning in life, help with finding hope, talking about death and dying, and finding peace of mind.[4][Level of evidence: II] It is appropriate to initiate such an inquiry once initial diagnosis and treatment issues have been discussed and considered by the patient (approximately a month after diagnosis or later). In a large, multisite, longitudinal study of patients with advanced cancer,[5][Level of evidence: II] there was considerable variation in whether spiritual concerns were addressed by medical staff, with about 50% reporting at least

2.

3.

Modes of Intervention Physicians Hospital Chaplains Support Groups Other Various modes of intervention or assistance might be considered to address the spiritual concerns of patients. These include the following:

some support at three of the settings, in contrast to fewer than 15% reporting some support at the other four settings. Support received from the medical team predicted greater quality of life, greater likelihood of receiving hospice care at the end of life, and for patients who have high levels of religious coping, less aggressive care. One trial,[6][Level of evidence: II] with a sample of 115 mixed-diagnosis patients (54% under active treatment), evaluated a 5-minute semistructured inquiry into spiritual and religious concerns. The four physicians personal religious backgrounds included two Christians, one Hindu, and one Sikh; 81% of patients were Christian. Unlike the historyoriented interviews noted above, this inquiry was informed by brief patient-centered counseling approaches that view the physician as an important source of empowerment to help patients identify and address personal concerns (see Table 2 below for the content). After 3 weeks, the intervention group had larger reductions in depression, had more improvement in quality of life, and rated their relationship with the physician more favorably. Effects for quality of life remained after statistically adjusting for change in other variables. More improvement was also seen in patients who scored lower in spiritual well-being, as measured by the Functional Assessment of Chronic Illness TherapySpiritual Well-Being (FACIT-Sp) at baseline. Acceptability was high, with physicians rating themselves as comfortable in providing the intervention during 85% of encounters. Seventy-six percent of patients characterized the inquiry as somewhat to very useful. Physicians were twice as likely to underestimate the usefulness of the inquiry to patients rather than to overestimate it, in relation to the patient ratings. The statements in Table 2 may be used to initiate a dialogue between health care provider and patient. Table 2. Exploring Spiritual/Religious Concerns in Adults a With Cancer Enlarge Health Care Provider Action
a

Health Care Provider Action inquiry to patients initial response.

Possible Patient Response

Health Care Provider Reply illness?

Neutral-Receptive Response

How might you draw on your faith or spiritual beliefs to help you? Many people feel that waywhat might help you come to terms with this? It sounds like youre uncomfortable that I brought this up. What Im really interested in is how you are copingcan you tell me about that? I see. Can you tell me more (about.)?

Spiritually Distressed Response (e.g., expression of anger or guilt) Defensive/Rejecting Response

Continue to explore further as indicated. Inquire about ways of finding meaning and a sense of peace. Inquire about resources. Offer assistance as appropriate and available.

Is there some way in which you are able to find a sense of meaning or peace in the midst of this? Whom do you have to talk to about this/these concerns? Perhaps we can arrange for you to talk to someone./Theres a support group I can suggest./There are some reading materials in the waiting room. I appreciate you discussing these issues with me. May I ask about it again?

Possible Patient Response

Health Care Provider Reply

Adapted from Kristeller et al.[6] When dealing with a serious illness, many people draw on religious or spiritual beliefs to help cope. It would be helpful to me to know how you feel about this. Positive-Active Faith Response What have you found most helpful about your beliefs since your Bring inquiry to a close.

Introduce issue in neutral inquiring manner.

Inquire further, adjusting

A common concern is whether to offer to pray with patients. Although one study [7] found that more than one half of the patients surveyed expressed a desire to have physicians pray with them, a large proportion does not express this

preference. A qualitative study of cancer patients [8] found that patients were concerned that physicians are too busy, not interested, or even prohibited from discussing religion. At the same time, they generally wanted their physician to acknowledge the value of spiritual and religious issues. A suggestion was made that physicians might raise the question of prayer by asking, Would that comfort you? The most important guideline is to remain sensitive to the patients preference; therefore, asking patients about their beliefs or spiritual concerns in the context of exploring how they are coping in general is a viable approach in exploring these issues. Hospital Chaplains Traditional means of providing assistance to patients has generally been through the services of hospital chaplains.[9,10] Hospital chaplains can play a key role in addressing spiritual and religious issues; chaplains are trained to work with a wide range of issues as they arise for medical patients and to be sensitive to the diverse beliefs and concerns that patients may have.[11] Chaplains are generally available in large medical centers, but they may not be available in smaller hospitals on a reliable basis. Chaplains are rarely available in the outpatient settings where most care is now delivered (especially early in the course of cancer treatment, when these issues may first arise). In a large, multisite, longitudinal study of patients with advanced cancer,[5][Level of evidence: II] only 46% of patients reported receiving pastoral care visits. While these visits were not associated with receipt of end-of-life care (either hospice or aggressive measures), they were associated with better quality of life near death. Another traditional approach in outpatient settings is having spiritual/religious resources available in waiting rooms. This is relatively easy to do, and many such resources exist; however, a breadth of resources covering all faith backgrounds of patients is highly desirable (refer to the Additional Resourcessection). Support Groups Support groups may provide a setting in which patients may explore spiritual concerns. If spiritual concerns are important to a patient, the health care provider may need to identify whether a locally available group addresses these issues. The published data on the specific effects of support groups on assisting with spiritual concerns is relatively sparse, partly because this aspect of adjustment has not been systematically evaluated. A randomized trial [12][Level of evidence: I] compared the effects of a mind-body-spirit group to a standard group support program for women with breast cancer. Both groups showed improvement in spiritual wellbeing, although there were appreciably more differential effects for the mind-body-spirit group in the area of spiritual integration.

A study of 97 lower-income women with breast cancer who were participating in an online support group examined the relationship between a variety of psychosocial outcomes and religious expression (as indicated by the use of religious words such as faith, God, pray, holy, or spirit). Results showed that women who communicated a deeper religiousness in their online writing to others were found to have lower levels of negative emotions, higher levels of perceived health selfefficacy, and higher functional well-being.[13] An exploratory study of a monthly spirituality-based support group program for African American women with breast cancer suggested high levels of satisfaction in a sample that already had high levels of engagement in the religious and spiritual aspects of their lives.[14][Level of evidence: III] One author [15] presents a well-developed model of adjuvant psychological therapy that uses a large group format and addresses both basic coping issues and spiritual concerns and healing, using a combination of group exploration, meditation, prayer, and other spiritually oriented exercises. In a carefully conducted longitudinal qualitative study of 22 patients enrolled in this type of intervention,[16] researchers found that patients who were more psychologically engaged with the issues presented were more likely to survive longer. Other approaches are available but have yet to be systematically evaluated,[17,18] have not explicitly addressed religious and spiritual issues, or have failed to evaluate the effects of the intervention on spiritual well-being.[19] Other Other therapies may also support spiritual growth and posttraumatic benefit finding. For example, in a nonrandomized comparison of mindfulness-based stress reduction (n = 60) and a healing arts program (n = 44) in cancer outpatients with a variety of diagnoses, both programs significantly improved facilitation of positive growth in participants, although improvement in spirituality, stress, depression, and anger was significantly larger for the mindfulness-based stress reduction group.[20][Level of evidence: II]