Uterine/Endometrial Cancer/GTD

Cancer of the uterus arises from either the smooth muscle component or the epithelial component known as the endometrium. Endometrial cancer is the most common gynecologic cancer and its incidence is rising. Cancer of the smooth muscle component of the uterus, known as uterine sarcoma, is very rare. On this page you will learn about symptoms of uterine cancer, diagnosis, treatment options, and hopefully help you prepare for a discussion with a Gynecologic Oncologist.

View the information in this section in our brochure, Endometrial Cancer: Your Guide available at the links below.

Uterine/Endometrial Cancer Overview

Cancer occurs when cells in an area of the body grow abnormally. Endometrial cancer is cancer of the lining of the uterus (called the endometrium). The uterus (or womb) is where a baby grows during pregnancy. The fallopian tubes and ovaries are on both sides of the uterus. The cervix is the mouth of the uterus (or womb) that connects it to the vagina. These reproductive organs are located in the pelvis, close to the bladder and rectum.

The endometrium is the inside lining of the uterus that grows each month during the childbearing years. It does this so that it will be ready to support an embryo if a person becomes pregnant. If pregnancy does not occur, the endometrium is shed during the menstrual period. Surrounding the endometrium is a thick layer of smooth muscle, which contracts during labor to deliver the baby. Cancer can occur in either the endometrium or the smooth muscle.

Uterine/Endometrial Cancer Symptoms

The most common warning sign for any uterine cancer is abnormal vaginal bleeding. Recognition of this symptom often affords an opportunity for early diagnosis and treatment. In postmenopausal people, any bleeding or spotting is abnormal and should prompt immediate evaluation by a gynecologist. Premenopausal reproductive age people who do not have regular monthly periods or who have excessive duration and/or quantity of bleeding each month should also be evaluated by a gynecologist as these can be symptoms of uterine cancer. Increasing pelvic pressure or abdominal girth, pelvic pain/fullness, increasing urinary frequency, or difficulty passing stool can sometimes be associated with an enlarging uterus. An enlarging uterus outside of pregnancy is often due to smooth muscle tumors and should be prompt evaluation by a gynecologist. Most smooth muscle tumors of the uterus are benign fibroids, but rarely these can be a malignant sarcoma.

Medical Evaluation and Diagnosis

When a person experiences concerning symptoms, a pelvic exam, including a rectovaginal exam, and a general physical should be performed. When the physical exam is abnormal and in most cases of abnormal bleeding or postmenopausal bleeding a pelvic ultrasound and/or endometrial biopsy will be obtained. Biopsy of the endometrium can be done in the office or by way of a D&C (dilation and curettage) procedure in the operating room.

If uterine cancer is suspected or diagnosed, it is important to seek care first from a gynecologic oncologist—medical doctors with specialized training in treating gynecologic cancers who can manage your care from diagnosis to completion of treatment. Use our Seek a Specialist tool to find a gynecologic oncologist in your area.

During your treatment, you will come in contact with many health care professionals—these people make up your treatment team. They will work with each other and you to provide the special care you need. Learn more about your treatment team.

Surgical Staging

Though the majority of uterine cancers are confined to the uterus, your treatment team may recommend more tests to determine if the cancer has spread. Additionally, specific procedures during surgery may be performed to determine the extent of disease. This process is called staging. Staging helps to determine the exact extent of your cancer and the best treatment plan for you.

Following surgery, your cancer will be categorized into Stage I, II, III, or IV. The cancer might also be assigned a grade. Grade refers to how abnormal the cells appear under a microscope. Low grade tumors, also called grade 1, have features that resemble normal endometrium cells. In contrast, in high grade tumors (grade 3) the microscopic appearance is greatly altered from normal.  Some varieties of endometrial cancer are not graded because they are high grade by nature and known to behave aggressively in general.  Most sarcomas are also considered high grade.

Uterine Cancer Stages

Stage 1:

The cancer is found only in the uterus. It has not spread to the cervix (opening of the uterus).

Stage 2:

The cancer has spread from the uterus to the cervix (opening of the uterus), but it has not gone any farther.

Stage 3:

The cancer has spread outside the uterus itself. It may have spread to nearby lymph nodes, ovaries, fallopian tubes, and vagina, but it has not gone outside the pelvic area. It has not spread to the bladder or rectum.

Stage 4:

The cancer has spread into the bladder or rectum and/or to other body parts outside the pelvis, such as the abdomen or lungs.

Uterine/Endometrial cancer treatment and side effects

Uterine cancer may be treated with surgery, radiation therapy, chemotherapy, or hormonal therapy. Depending on your situation, your treatment team may recommend using a combination of therapies to treat your cancer.

All treatments for uterine cancer have side effects, but most side effects can be managed or avoided. Treatment may affect various aspects of your life, including your function at work, home, intimate relationship, and deeply personal thoughts and feelings..

Before beginning treatment, it is important to learn about the possible side effects and talk with your treatment team members about your feelings or concerns. They can prepare you for what to expect and tell you which side effects should be reported to them immediately. They can also help you find ways to manage the side effects that you experience.

Understanding the Goals of Treatment

As you begin your treatment, make sure that you understand what to expect. Is this for cure? What are the chances of cure? If there is no cure, will the treatment make me live better or longer? It is very important to understand the truth about what to expect from the treatment—and what are the potential costs of side effects, expenses, etc.—so that you can make the best decisions for yourself and the life you want to lead.

Uterine Cancer Treatment Options

The most common treatment for endometrial cancer is surgery. Several types of surgery can be performed.

Hysterectomy (total) involves removal of the uterus, cervix, fallopian tubes, and ovaries and is the standard procedure for treating endometrial cancer. The uterus, cervix, fallopian tubes, and ovaries can be removed in one of two ways:

  • Total abdominal hysterectomy: The uterus, cervix, fallopian tubes, and ovaries are taken out through an incision in the abdomen.
  • Minimally invasive hysterectomy (laparoscopic-assisted vaginal hysterectomy and robotic-assisted laparoscopic hysterectomy): The uterus, cervix, fallopian tubes and ovaries are taken out through the vagina with the assistance of a laparoscope or robotic device (with a camera attached) that is placed through the abdomen via a small incision.

For patients with multiple medical problems who are not healthy enough to undergo an extensive surgical procedure, a vaginal hysterectomy is another option, although some patients are not surgical candidates. In most cases, both ovaries and both fallopian tubes must also be removed. This procedure is called a bilateral salpingo-oophorectomy.

In addition to these procedures, lymph nodes in the abdomen and pelvis may also be removed to see whether they contain cancer.

Side effects of surgery

Some discomfort is common after surgery. It often can be controlled with medicine. Tell your treatment team if you are experiencing any pain. Other possible side effects are:

  • Nausea and possible vomiting
  • Fevers
  • Infections
  • Wound problems
  • Anemia
  • Swelling of the legs caused by lymphedema
  • Blood clots
  • Difficulty urinating or constipation

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected into a vein). You may be treated in the doctor’s office or the outpatient part of a hospital.

The drugs travel through the bloodstream to reach all parts of the body. This is why chemotherapy can be effective in treating endometrial cancer that has spread beyond the uterus. However, the same drugs that kill cancer cells may also affect healthy cells.

Another method of delivering chemotherapy drugs is intraperitoneal (IP) therapy, which is the delivery of anti-cancer drugs directly into the peritoneal space (abdominal cavity), the space that lies between the abdominal muscles and abdominal organs.

To limit the damage to healthy cells, chemotherapy is usually given in cycles. Periods of chemotherapy are alternated with rest periods, during which no chemotherapy is given. Some side effects may still occur.

Most people with endometrial cancer receive intravenous chemotherapy that is usually given after surgery, but in some cases, it may be given prior to hysterectomy surgery. Commonly used chemotherapy drugs include: carboplatin, cisplatin, paclitaxel, docetaxel, doxorubicin, and others. These medications are given alone or in combination. The combination of carboplatin and paclitaxel is the most commonly used therapy for patients requiring chemotherapy for endometrial cancer.

Side effects of chemotherapy

Each person responds to chemotherapy differently. Some people may have very few side effects, while others experience several. Most side effects are temporary. They include:

  • Nausea
  • Loss of appetite
  • Mouth sores
  • Increased chance of infection
  • Bleeding or bruising easily
  • Hair loss
  • Fatigue

Radiation therapy (also called radiotherapy) uses high-energy x-rays, or other types of radiation, to kill cancer cells or stop them from growing.

Radiation therapy can be used:

  • Instead of surgery to treat early-stage endometrial cancer, although this is uncommon.
  • Before surgery, to shrink the cancer (called neoadjuvant therapy).
  • After surgery, to kill any cancer cells that may have spread to other tissues within the pelvis (called adjuvant therapy).

Two types of radiation therapy are used to treat endometrial cancer:

  • External radiation therapy uses a machine that directs the x-rays toward a precise area on the body. The therapy is usually given every day for about 6 weeks. It does not hurt and only takes a few minutes each day. You can be treated at a clinic, hospital or radiation oncology office.
  • Internal radiation therapy (also called brachytherapy) involves placing a small capsule of radioactive material inside the vagina. This procedure can be performed either on an inpatient or outpatient basis, depending on your treatment team’s recommendation.

Side effects of radiation

The side effects of radiation therapy depend on the dose used and the part of the body being treated. Common side effects include:

  • Dry, reddened skin in the treated area
  • Fatigue
  • Diarrhea
  • Discomfort when urinating
  • Narrowing of the vagina
  • Anemia

Most of these side effects are temporary. Be sure to talk with your treatment team members about any side effects that you experience. They can help you find ways to manage them.

Some types of endometrial cancer have hormone receptors that can be targeted to prevent their growth. In such cases, hormone therapy is a treatment option. Hormone therapy can block these receptors and inhibit female hormones as a way of preventing endometrial cancer cells from getting or using the hormones they may need to grow. It is usually taken as a pill but can be given as a shot.

Side effects of hormone therapy

The side effects of hormone therapy depend on the type of hormones being used. Some people retain fluid and have a change in appetite or have hot flashes. Other hormones can sometimes cause blood clots.

We’re excited to share news about immunotherapies, one of the most promising treatments to emerge for gynecologic cancer. Before immunotherapies, cancer treatment included surgery, radiation, chemotherapy and hormonal therapy. Immunotherapies are showing benefits in prolonged disease control, or longer survival rates.

Pembrolizumab is one of several new immunotherapies developed recently and has been approved to treat certain types of gynecologic cancers, including uterine and cervical. Pembrolizumab could provide benefit for up to 30 percent of patients with advanced endometrial cancer.

PARP inhibitors are another recent breakthrough in cancer treatment. PARP inhibitors are being developed for multiple indications, the most significant being the treatment of ovarian cancer. Experts say they are changing the landscape for ovarian cancer treatment.

Another innovative treatment method, sentinel lymph node mapping, is changing the standard of care for some gynecologic cancers. Sentinel lymph node mapping can safely replace pelvic lymphadenectomy in staging certain types of cancer such as endometrial. And for patients with early stage vulvar cancer, sentinel lymph node biopsy has become the new standard of care.

Genetic testing is another area in gynecologic oncology that continues to evolve. Genetic tests now screen not only for BRCA1 and BRAC2, the most common gene mutations, but for a complete panel of genes less frequently associated with the risk for developing breast or ovarian cancer. Researchers also are working to develop a test that can diagnose ovarian cancer in its earliest stages.

Survival rates for many types of gynecologic cancer continues to climb. Advances are being made every year. But funding for clinical trials has been eroded. Rare cancers are challenging to study due to their low incidence rates.

The SGO and FWC remain undeterred, however, in our collective goal to continue to advance innovation to eradicate gynecologic cancer. Please click on one of the major cancer types to discover more about recent advances made in the prevention, detection and treatment of gynecologic cancer.

This section provided through a generous unrestricted educational sponsorship from Eisai. Content excludes editorial input.

Uterine/Endometrial Cancer and Genetics

Most uterine cancers are sporadic with no inherited genetic risk. 5-10% of endometrial cancers can be the result of an inherited mutation in either MLH1, MLH2, MSH6, or PMS2 genes which are diagnostic of Lynch Syndrome. People with Lynch Syndrome have increased risks of multple types of cancers including endometrial and ovarian. If you are diagnosed with endometrial cancer, be sure to ask your doctor if they tested for Lynch Syndrome. A very small subset of patients with serous endometrial cancer could have an inherited underlying BRCA1 mutation as the cause of their disease, however no clear guidelines for genetic testing for BRCA1 mutations exist. Uterine sarcomas are almost never associated with an inherited genetic mutation.

Follow up after treatment

The frequency of exams, imaging, and blood tests varies because of many factors. Typically, you will be followed every 3 to 6 months for the first 2 years with at least an examination of the vagina and rectum to detect any recurrences early at the most curable stage. These examinations will occur less frequently thereafter. In addition, imaging studies such as x-rays, CT scans, or MRIs may be periodically performed, especially if you have any new pains or symptoms. The top of the vagina is the most common site of recurrent endometrial cancer, and patients will typically present with vaginal bleeding.

Recurrent disease

If your cancer recurs, there are several options for treatment. These include repeat surgery, re-treatment with the same chemotherapy given initially, treatment with a different type of agent (chemotherapy, hormonal, or targeted therapy) and sometimes radiation therapy. As each recurrence will be different, it is important to discuss your individual situation with your team. It is also important to investigate whether there is a clinical trial that is appropriate for you. Don’t be afraid to seek a second opinion.

Isolated vaginal recurrences can often be cured so early detection and recognition of abnormal symptoms is critical. Notify your physician if you develop abnormal bleeding or other unusual pelvic symptoms following treatment for endometrial cancer.

Importance of Participation in Clinical Trials

There are many ongoing clinical trials studying new and better ways to treat endometrial cancer. Many treatment options are available today because women diagnosed with endometrial cancer were willing to participate in prior clinical trials.

Clinical trials are designed to test some of the newest and most promising treatments for endometrial cancer. The Foundation for Women’s Cancer (FWC) partners with NRG Oncology (formerly Gynecologic Oncology Group), part of the National Cancer Institute cooperative group working only on gynecologic cancer clinical trials, and others to make information about current clinical trials available. For more information about clinical trials available for enrollment, visit ClinicalTrials.gov.

Gestational trophoblastic disease (GTD)

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumors. According to the American Cancer Society, GTD occurs in about 1 pregnancy out of 1,000 in the US—most of these are hydatidiform moles. If you and your family have learned of a GTD diagnosis, the amount of information you receive at the time of diagnosis can feel overwhelming. We hope this information will help you understand the condition more thoroughly and help you through this difficult time.

GTD Overview

GTD is a rare group of interrelated tumors that develop following conception that lead to abnormal development of the placenta. More than 80 percent of GTD cases are non-cancerous. All forms of GTD can be treated and in the great majority of cases the treatment results in a cure. Most women who have had a single incidence of GTD can go on to have normal pregnancies.

Medical Evaluation and Diagnosis

The diagnosis of hydatidiform mole is most commonly made by an ultrasound, a test which uses sound waves to show the contents of the uterus. The ultrasound picture of a complete hydatidiform mole will show the uterus filled with cysts. There is no evidence of a fetus.

The early diagnosis of a partial hydatidiform mole will look like a miscarriage or show an abnormal fetus with an abnormal placenta depending upon the number of weeks pregnant. In most cases of partial mole, the diagnosis is made by the pathologist. A blood test will also be done to look for a hormone called human chorionic gonadotropin (known as hCG or beta-hCG) which is also present in normal pregnancy. This hormone is an important test which will be used to determine whether the molar pregnancy will become malignant, to determine if treatment is working, and to find out if the GTD has returned.

The diagnosis of choriocarcinoma is usually made when the patient develops abnormal vaginal bleeding or other symptoms, or on rare occasions when a pregnancy test is found to be elevated and there is no pregnancy.

Malignant GTD stages

Stage 1:

The cancer has not spread from the uterus.

Stage 2:

The cancer has spread from the uterus to other structures in the pelvis.

Stage 3:

The cancer has spread to the lungs.

Stage 4:

The cancer has spread to other organs.

GTD treatment and side effects

After the diagnosis of complete or partial hydatidiform mole is made or suspected, the uterine contents are removed by dilation and evacuation (D&E). Hysterectomy may be advisable in older patients who have completed childbearing to reduce the risk of malignancy. After the uterus is emptied, testing for human chorionic gonadotropin should be performed every week in order to determine if the molar pregnancy is malignant. If the molar pregnancy is benign the hormone level will become undetectable in 8-12 weeks. Hormone testing should be continued until three weekly negative levels are obtained, then followed by monthly tests for six months, after which pregnancy is permitted. During the six month follow-up it is important to avoid pregnancy. The use of oral contraceptives is safe.

A rise in the hormone level indicates that the molar pregnancy is malignant GTD (also called gestational trophoblastic neoplasia, GTN). More tests will be done to find out if the cancer has spread from the uterus to other parts of the body—this is called staging. Even if GTD has spread to other parts of the body, it is still highly curable.

The treatment of malignant GTD depends on the stage and number of risk factors which determine the type of drugs that will most likely cure the disease. The factors that are characteristic of women who are likely to be cured by one or more single chemotherapy drugs (called low-risk malignant GTD) are:

  • The last pregnancy was less than 4 months ago
  • The level of hCG in the blood is low
  • The cancer has not spread to the liver, brain or other distant organs
  • The patient has not received chemotherapy treatments earlier

The risk factors of women who develop malignant GTD who are NOT likely to be cured by one or more single chemotherapy drugs and who require treatments containing multiple agents to effect cure (called high-risk malignant GTD) are:

  • The last pregnancy was more than four months ago
  • The level of hCG in the blood is high
  • The cancer has spread to the liver, brain and/or other distant organs
  • The patient received chemotherapy earlier and the cancer did not go away
  • The tumor began after completion of a normal pregnancy

Three kinds of treatment are used for malignant GTD: surgery (removing the cancer), chemotherapy (using drugs to kill the cancer) and radiation therapy (uses high energy x-rays to kill cancer cells and shrink tumors). The most common operation used for malignant GTD is hysterectomy, an operation to take out the uterus. Surgery may also be used to remove cancer involving the lungs and other organs which have not gone away with drug therapy.

Types and symptoms of GTD

Hydatidiform mole (also called a “molar pregnancy”) is a form of GTD that arises when fertilization of an egg cell results in an abnormal pregnancy. There are two types of molar pregnancies, complete and partial. A complete molar pregnancy develops when the fertilized egg cell lacks maternal genes. The pregnancy that results contains no fetal tissue and resembles grape-like cysts that fill the uterine cavity. A partial molar pregnancy occurs when more than one sperm fertilizes a normal egg resulting in a pregnancy where both the fetus and placenta are abnormal. The term partial is used because the placenta contains both normal tissue and grape-like cysts similar to that seen in complete moles. 80 percent of molar pregnancies are benign in that they cause no further trouble after they are removed from the uterus. However, in approximately 20 percent of complete molar pregnancy and one to four percent of partial moles, the molar tissue either spreads locally within the muscular wall of the uterus (called invasive mole) or spreads more widely to other parts of the body, most commonly the lungs (called metastases), which requires treatment. Hydatidiform moles occur in only one of every 1000-1200 pregnancies in the United States.

Symptoms

The most common symptoms of hydatidiform mole are feeling pregnant and vaginal bleeding, which can be either bright red or watery brown discharge. Other symptoms are:

  • Abdominal bloating
  • Nausea and vomiting which is generally more severe than in normal pregnancy
  • Fatigue, shortness of breath and lack of energy due to anemia, if there has been a great deal of blood loss
  • Signs of an overactive thyroid gland including rapid heartbeat, warm skin and mild shaking seen rarely in patients with complete mole.
  • High blood pressure due to pre-eclampsia (also called toxemia of pregnancy) which can develop if the molar pregnancy continues beyond twelve weeks

Choriocarcinoma is a highly malignant form of GTD that spreads rapidly throughout the body and requires vigorous treatment. It may have begun as a molar pregnancy or from tissue that remains in the uterus following a miscarriage or childbirth. Choriocarcinoma is even less common, arising in only one of every 20,000-40,000 pregnancies.

Symptoms

Women who develop choriocarcinoma may be symptom-free or experience symptoms based on which organ(s) are involved:

  • Uterus: Vaginal bleeding, discharge
  • Lung: Coughing up blood, shortness of breath or chest pain
  • Liver: Abdominal pain
  • Brain: Headache, trouble with vision, convulsion, weakness or loss of function
  • Kidney: Blood in urine
  • Bowel: Blood in stool

Placental-site trophoblastic tumor is a very rare form of the disease that arises in the uterus at the site where the placenta was attached. These tumors penetrate the muscle layer of the uterus and usually do not spread to other parts of the body.

GTD treatment options

Chemotherapy is the main treatment for malignant GTD and is generally highly effective. Chemotherapy uses drugs to kill cancer cells. It may be taken by pill, or by a needle in vein or muscle. It is called systemic treatment because the drugs enter the bloodstream, travel through the body and can kill cancer cells outside the uterus. Chemotherapy may be given before or after surgery or alone. Patients can preserve fertility and still be cured with chemotherapy even in the presence of widespread disease.

Radiation may infrequently be used in certain cases to treat cancer that has spread to other parts of the body, particularly the brain. Radiation may come from a machine outside the body (external-beam radiation therapy) or from putting materials that produce radiation (radioisotopes) through thin plastic tubes into the area where the cancer cells are found (internal radiation).

Placental site trophoblastic tumors, unlike choriocarcinoma, are not very sensitive to chemotherapy. Since in most cases the tumor is localized to the uterus, hysterectomy is generally curative. When the disease spreads outside the uterus, high dose chemotherapy is used with some success.

Follow up after treatment

Hormone follow-up by measuring the level of hCG in the blood continues until the hormone level is normal for three weeks, then should continue monthly for 12 months (24 months or patients with Stage IV disease). During that time the patient should avoid pregnancy. Women who conceive within 12 months of completing chemotherapy have an increased risk of miscarriage, particularly if they have received multiple chemotherapeutic agents. If pregnancy occurs before follow-up is complete, tumor relapse may be difficult to detect and diagnosis of relapse may be delayed.

The chemotherapy used for the treatment of malignant GTD is generally well tolerated without long-term side effects with two exceptions:

  • The use of multi-agent chemotherapy is associated with an earlier menopause.
  • Women with high-risk GTN who require multi-agent chemotherapy which includes a drug called etoposide and survive for more than 25 years should be advised that they may be at increased risk of developing secondary tumors, particularly acute myeloid leukemia, colon cancer, melanoma and breast cancer.

Recurrent disease

GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and women with malignant GTD (called GTN) usually have a very good prognosis. Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumor and life-threatening disease, it is very sensitive to chemotherapy. 85 to 90 percent of women with low-risk malignant GTD are cured by the initial chemotherapy and the remaining are cured by the use of stronger combinations of drugs or surgery. Similarly, 85 to 90 percent of women who develop high-risk malignant GTD are cured by chemotherapy used together with the selective use of surgery and radiation. Approximately ten to 15 percent of women with high-risk malignant GTD will develop drug resistance after prolonged chemotherapy. This group is made up of patients with stage IV disease that involves distant organs such as the brain, liver and bowel. Specially designed chemotherapy treatments using drugs that have been shown to be effective against other cancers are being employed to prolong life for many of these women.

Becoming Pregnant Again

After completing hormone follow-up for hydatidiform mole, women may try for pregnancy whenever they wish. The risk of another molar pregnancy is low. More than 98 percent of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk for complications. Since patients with hydatidiform mole are at increased risk of another molar pregnancy, it is advisable for them to undergo ultrasound examinations at ten weeks of gestation to determine if the pregnancy is progressing normally.

Most women who require treatment for malignant GTD can become pregnant again and can have normal pregnancy outcomes. After chemotherapy is completed women should postpone pregnancy for 12 months (24 months for women with stage IV disease) while they are being followed with hormone testing to make sure the tumor does not recur. There does not appear to be an increase rate of congenital malformation irrespective of the chemotherapy used. Following GTD the expectation of normal future pregnancy is about comparable to the general population.