What is Uterine Cancer? Symptoms, Diagnosis and Treatments

Table of Contents

Uterine cancer, also known as endometrial cancer, is a type of cancer that affects women.

Endometrial cancer begins when cells in the endometrium, or the lining of the uterus, start to grow out of control.

These cells begin to change and form a mass known as a tumor.

A tumor can be benign or cancerous.

When a tumor is cancerous, it can grow and spread to other areas of the body.

A woman’s uterus is a hollow organ typically the size and shape of a pear.

It’s in the uterus that a fetus develops during pregnancy and this organ is comprised of two parts: the cervix, which is the lower end that extends into the vagina, and the body or corpus, the upper part of the uterus.

The body of the uterus is made up of an outer layer of muscle (myometrium) and an inner lining called the endometrium.

During the menstrual cycle, hormone changes cause changes in the endometrium of the uterus.

Early in the cycle, before ovulation, the ovaries produce estrogen.

Estrogen thickens the endometrium to nourish an embryo if the egg is fertilized and pregnancy occurs.

If there is no pregnancy, lower levels of estrogen are produced and more progesterone is made after ovulation to prepare the innermost layer of the endometrium to shed.

At the end of the cycle, the shed lining becomes the menstrual flow.

While there are two types of uterine cancer (uterine sarcomas that begin in the muscle layer of the uterus and endometrial carcinomas that start in the endometrium), virtually all uterine cancer begins in the endometrium.

There are several forms of endometrial cancer that are classified according to how the cells appear under a microscope:

  • Adenocarcinoma, which is the most common. There are also many subtypes of adenocarcinoma.
  • Carcinosarcoma
  • Squamous cell carcinoma
  • Transitional carcinoma
  • Small cell carcinoma
  • Undifferentiated carcinoma

Along with classifying the appearance of the cells, uterine cancer is also graded based on how much cancer forms glands that appear similar to those in healthy endometrium.

In grades 1 and 2 cancers, most of the cancerous tissue forms glands.

In grade 3, more of the cancer cells are arranged in a disorganized fashion and do not form glands.

This grading is important because it dictates how aggressive the cancer is likely to be.

Type 1 endometrial cancers are believed to be caused by excess estrogen in the body and they usually do not spread quickly.

Type 2 cancers are more likely to spread and are not believed to be caused by excess estrogen.

Grade 3 uterine cancers are usually aggressive with a poorer prognosis.

 

History

Worldwide, about 320,000 women are diagnosed with endometrial cancer every year, and 76,000 die from the disease.

Endometrial cancer is now the 4th most common cancer and accounts for 7% of all female cancers after breast, lung, and colorectal cancers.

Among cancers that only affect women, endometrial cancer is third behind ovarian and cervical cancer.

Fortunately, endometrial cancer has a favorable prognosis for most women and results in just 4% of cancer deaths among women.

A dramatic increase in the rate of uterine cancer occurred in North America between 1960 and 1975, which was widely interpreted to be the result of an increase in the use of estrogen-only hormone therapy, now known to be a major risk factor for the disease.

The first cases of uterine cancer related to estrogen hormone therapy were reported in the 1960s.

Between 1960 and 1970, the sale of oral estrogen tripled in the United States and reached a peak of 17 million prescriptions.

By the early 1980s, the incidence rates for uterine cancer returned to previous levels and remained there for some time.

The rate of endometrial cancer is rising once again due to increasing rates of obesity in developed countries and higher populations of elderly and post-menopausal women.

Rates of uterine cancer have increased in numerous countries between 1980 and 2010.

The lifetime risk of uterine cancer for women in developed nations is 1.6% compared to just 0.6% in developing nations.

It’s estimated that 17% to 46% of endometrial cancer cases are related to diabetes.

The link between uterine cancer and Polycystic Ovary Syndrome (PCOS), meanwhile, was first reported in the 1940s and 1950s, with more modern studies reporting up to one-third of pre-menopausal women with uterine cancer having PCOS.

Today, the 5-year survival rate for endometrial cancer is 82%, which means 82% of women diagnosed with uterine cancer will survive for 5 years.

The 10-year survival rate is 79%.

When the cancer is still local when it is diagnosed (still in the uterus), the 5-year survival rate is 95%.

If cancer has spread regionally at diagnosis, the 5-year survival rate is 68%.

The 5-year survival rate when cancer has spread more distantly is 17%.

 

Risk Factors

Researchers have identified many risk factors for the development of uterine cancer.

While some factors can increase your risk of developing uterine cancer, they do not always cause cancer.

There are also many women who develop uterine cancer who have no known risk factors for the disease.

Hormones play a major role in the development of endometrial cancer.

Many risk factors of the disease are related to estrogen levels.

Prior to menopause, the ovaries are the main source of estrogen and progesterone, two female hormones.

The balance between these hormones changes during a woman’s menstrual cycle, but a shift toward more estrogen can raise the risk of cancer.

The most common risk factors for endometrial cancer include:

  • Age. Most women diagnosed with uterine cancer are over 50 years of age and have gone through menopause.
  • The number of menstrual cycles. Women who started their period before 12 and/or went through menopause after 50 have a higher risk of endometrial cancer.
  • Childbearing. Women who have never been pregnant or given birth have a higher risk of developing the disease.
  • Obesity. Fat tissue produces higher levels of estrogen, especially after menopause, which raises the risk of this type of cancer. Uterine cancer is twice as common among overweight women and three times more common among obese women compared to women who maintain a normal weight.
  • Diabetes. While the exact relationship is unknown, uterine cancer is more common among women with diabetes. It’s believed to be related to higher obesity rates in people with type 2 diabetes.
  • Family history. Women who have a family history of ovarian, uterine, or colon cancer have a higher risk of developing uterine cancer.
  • Ovarian syndromes and tumors. Some ovarian conditions like Polycystic Ovarian Syndrome (PCOS) and ovarian tumors increase estrogen levels and increase the risk of uterine cancer.
  • Estrogen replacement therapy. This type of hormone therapy without progesterone after menopause raises the risk of cancer. To lower this risk, women now usually treated with estrogen and progesterone in an approach called combination hormone therapy.
  • Tamoxifen. Research has found women who are treated with Tamoxifen (a breast cancer medication) have a higher risk of endometrial cancer.

There are also many factors associated with a lower risk of endometrial cancer.

As with risk factors for the disease, many protective factors influence hormones.

The following factors can reduce the risk of developing uterine cancer:

  • Birth control medication. Women who take birth control pills have a lower risk of the disease. The risk is lowest among women who take the pill for a long time. Research shows the protective effect of birth control lasts for a minimum of 10 years after a woman discontinues oral contraceptives.
  • Pregnancy. Having many pregnancies guards against endometrial cancer by shifting the hormone balance more toward progesterone instead of estrogen. Women who have never been pregnant have a higher risk of the disease, especially women who were infertile.
  • Intrauterine device. Women who used an intrauterine device (IUD) for birth control have a lower risk of uterine cancer. This protective benefit is only known with IUDs that do not contain hormones.
  • Exercise. Physical activity has been found to reduce the risk of uterine cancer. Women who lead a sedentary life have a higher risk of the disease.

While there is no guaranteed way to prevent uterine cancer, women can reduce their risk for the disease by taking birth control pills, especially for a long period of time; maintaining a healthy weight; managing diabetes by regularly monitoring blood glucose levels; and carefully considering the risk of starting hormone replacement therapy, especially estrogen replacement alone.

 

Screening

Early detection of endometrial cancer before it spreads to other areas can dramatically improve the prognosis of the disease.

Unfortunately, uterine cancer can become advanced before any symptoms are noticed, especially among women who do not develop abnormal bleeding or discharge.

There are currently no screening tests available to detect endometrial cancer early in women who are at average risk of developing the disease.

At menopause, the American Cancer Society recommends women be educated on the signs and risks of uterine cancer and to report any vaginal spotting, discharge, or bleeding to their doctor.

Regular pelvic exams are also recommended.

Pelvic exams can detect many forms of cancer, including some types of advanced uterine cancer, although they cannot be used to detect early uterine cancer.

In some cases, the Pap test, which screens for cervical cancer, detects early endometrial cancers.

Still, the Pap test is not a good screening test for uterine cancer as it will be normal 50% of the time for this cancer.

A pap smear test can detect if endometrial cancer has spread to the cervix, however.

Women who are at an increased risk of uterine cancer, including women who have diabetes, infertility, obesity, high blood pressure, or are past menopause, should be advised about the symptoms and risks of endometrial cancer.

Women who have hereditary non-polyposis colon cancer (HNPCC) and those who have a close relative with the disease or cancer can undergo genetic testing to look for a gene mutation associated with HNPCC.

Women who have or may have HNPCC and those known to carry an HNPCC gene mutation are advised to get a yearly endometrial biopsy beginning at the age of 35.

A biopsy involves removing a tiny sample of endometrial tissue for testing in a lab.

With uterine cancer, a biopsy is the only sure way to determine whether an area has cancer.

An endometrial biopsy is rather invasive and requires inserting a tube into the uterus through the cervix to remove a tissue sample via suction.

Many women experience cramps and bleeding after the biopsy.

 

Symptoms

There are several symptoms that may indicate uterine cancer. Unfortunately, many signs only become apparent once cancer becomes advanced.

The most common sign of uterine cancer is unusual vaginal bleeding or discharge, which is reported in 90% of women diagnosed with uterine cancer.

This symptom may involve a change in periods, bleeding between periods, or bleeding after menopause.

While irregular bleeding can occur with several non-cancerous conditions, it’s important to have it investigated right away.

Some women also report non-bloody vaginal discharge.

This is found in about 10% of endometrial cases.

Many women with uterine cancer also report pelvic pain or pressure during intercourse and at other times.

While this can be a sign of a less serious problem, it can point to cancer if it is accompanied by abnormal vaginal bleeding or discharge.

This symptom tends to be more common in the later stages of cancer.

In the later stages of endometrial cancer, some women also report feeling a mass or tumor in their abdomen and weight loss without trying.

While abnormal bleeding or discharge is a very common symptom of endometrial cancer, it’s important to realize that some women experience no symptoms at all.

 

Diagnosis and Stages

A diagnosis of endometrial cancer is first made through a physical exam.

While the results of a pelvic exam are usually normal, especially in the early stages of uterine cancer, it is possible to detect changes in the consistency, size, and shape of the uterus and supporting structures when the disease is advanced.

There are several tests physicians may use to confirm uterine cancer.

  • Pap Test

A Pap test or pap smear is often done in conjunction with a pelvic exam.

This test is primarily used to check for cervical cancer, but it can sometimes find abnormal glandular cells caused by endometrial cancer.

  • Transvaginal Ultrasound

A transvaginal ultrasound can be used to check the endometrial thickness in women who are experiencing post-menopausal bleeding.

This imaging test can also be used to help indicate whether the thickness of the tissue seems cancerous.

Ultrasound findings alone cannot be used to make a diagnosis, so the test will be used with another diagnostic tool like an endometrial biopsy.

This test involves inserting an ultrasound wand into the vagina and aiming it at the uterus to obtain pictures of the internal organs.

  • Endometrial Biopsy

Either a biopsy of endometrial tissue or a dilation and curettage (D&C) are used to obtain tissue samples to check for cancer.

An endometrial biopsy is usually the first choice as it’s less invasive, although it may not give conclusive results.

During an endometrial biopsy, a small tube is inserted through the vagina and into the uterus where a tissue sample is removed with suction.

Women who have abnormal bleeding before a biopsy may still require a D&C.

  • Dilation & Curettage (D&C)

D&C has been recently found to give a higher false-negative rate than endometrial biopsy, which means it is more likely to indicate there is no cancer when there is.

During this test, a woman is given anesthesia to block pain.

It’s often done in conjunction with a hysteroscopy in which a thin, flexible tube is inserted through the vagina and into the uterus to visualize the uterus.

  • Hysteroscopy

This test is used to see the gross anatomy of the endometrium.

It usually can’t be used to indicate whether cancer is present, but it may be used in conjunction with a biopsy and to confirm a cancer diagnosis.

  • CT Scan

A CT scan creates 3D pictures of the inside of the body from x-rays taken from various angles.

A CT scan is typically only used to get a pre-operative image of a tumor that seems advanced during a physical exam or may have a high risk of metastasis.

  • MRI

An MRI uses magnetic fields rather than x-rays to produce images of the body.

An MRI may be used to help determine if endometrial cancer has spread to the cervix and to check nearby lymph nodes for cancer.

After uterine cancer is diagnosed, it is staged.

Staging involves analyzing all of the information available to determine how much cancer has spread.

The stage and grade of the uterine cancer are essential in choosing the right treatment plan and giving a prognosis.

Staging will involve classifying cancer based on the extent of the tumor, whether it has spread to lymph nodes, and whether it has spread to more distant sites.

Doctors will be unsure of the stage of cancer until the surgery is completed as cancer must be staged by examining tissue removed during surgery.

There are two systems used to stage uterine cancer: the more familiar FIGO system and the TNM staging system.

 

TNM Staging

Tumor Extent (T):

  • T0 means there is no sign of a tumor.
  • Tis means there is pre-invasive cancer that is only found on the surface layer of the endometrium.
  • T1 means the cancer is only growing in the uterus body and not into supporting connective tissue.
  • T2 means cancer has spread into the cervix but remains in the uterus.
  • T3 means cancer has spread outside of the uterus has not spread to the inner lining of the urinary bladder or rectum.
  • T4 means cancer has spread to the inner lining of the bladder or rectum.

Lymph Node Spread (N):

  • NX means the spread can’t be assessed.
  • N0 means cancer has not spread to the lymph nodes.
  • N1 means cancer has spread to pelvic lymph nodes.
  • N2 means cancer has spread to lymph nodes that are along the aorta.

Distant Spread (M):

  • M0 means cancer has not spread to distant organs, lymph nodes, and tissue.
  • M1 means cancer has spread to distant areas.

FIGO Stages of Uterine Cancer

Most people are more familiar with the FIGO cancer stages:

  • Stage 0 means the cancer is only found in the surface layers of the endometrium.
  • Stage I means the cancer is only found in the body of the uterus.
  • Stage II means cancer has spread to supporting connective tissue of the cervix but remains in the uterus.
  • Stage III means cancer has spread outside of the uterus or has spread to the pelvic area.
  • Stage IV means cancer has spread to the inner surface of the rectum or urinary bladder, to lymph nodes in the groin, or distant areas like the lungs or bones.

Uterine cancer often metastasizes to the Fallopian tubes and the ovaries.

If the lymphatic system is involved, the para-aortic and pelvic nodes are usually the first to become involved in cancer.

Uterine cancer can also metastasize to the blood and spread to the lungs, brain, bone, and liver.

In about 25% of cases, endometrial cancer metastasizes to the lungs.

 

Treatments and Drugs

Uterine cancer treatment involves an entire team of health care professionals who work with the patient to develop a customized treatment plan specific to the cancer type, stage, and grade.

This multidisciplinary team may include a gynecologic oncologist, physician assistants, social workers, oncology nurses, counselors, dietitians, pharmacists, and more.

Endometrial cancer is generally treated with one or more treatments such as surgery, hormone therapy, chemotherapy, and/or radiation therapy.

Treatment recommendations will depend on the stage and type of cancer, the woman’s overall health, the woman’s age, the woman’s preferences, potential side effects, and more.

  • Surgery

Surgery involves the removal of the cancerous tumor and surrounding tissue and it’s usually the first treatment used.

Depending on the stage and location of cancer, different surgical procedures can be used.

One of the most common is a hysterectomy.

This may be a simple hysterectomy (or removing the cervix and uterus) or radical hysterectomy (which involves removing the cervix, uterus, the upper part of the vagina, and nearby tissue).

If the woman has already gone through menopause, both fallopian tubes and ovaries may also be removed.

A hysterectomy offers the best hope to stop cancer, especially if it is contained to the uterus, although it will render the woman unable to become pregnant.

Other surgeries that may be used include lymph node dissection or removing lymph nodes near the tumor, and sentinel lymph node biopsy, which helps the surgeon determine if cancer has spread to the lymph nodes.

Surgery comes with short-term and long-term consequences.

Most women will require a stay in the hospital for several days and a recovery process that can take weeks.

The inability to become pregnant can be especially concerning for some women who may prefer to explore other treatment options like less extensive surgery followed by hormone therapy.

  • Radiation Therapy

Radiation therapy involves using high-energy x-rays to target and kill cancer cells.

Radiation is performed by a radiation oncologist who will develop a radiation therapy schedule with a specific number of treatments over a period of time.

Some women require both surgery and radiation therapy, which is usually performed after surgery to destroy remaining cancer cells.

Radiation therapy does have side effects that may include nausea, fatigue, skin reactions, loose bowel movements, and difficulty eating.

Most side effects go away once the treatment is over, but there some long-term side effects affecting bowel function and vaginal symptoms that may occur.

  • Chemotherapy

Chemotherapy uses medications to destroy cancer cells.

Most chemotherapy drugs work by preventing the cells from growing and dividing.

When chemotherapy is used to treat uterine cancer, it’s usually done after surgery.

It may be done in conjunction with radiation therapy or it may be done instead.

Chemotherapy can be administered by an IV placed in the vein or orally.

An oncologist will develop a personalized chemotherapy schedule that includes a specific number of cycles over a period of time.

Sometimes only one chemotherapy drug is used, but some cases call for the use of a combination of drugs.

Chemotherapy can have a number of side effects including fatigue, nausea, vomiting, hair loss, loss of appetite, diarrhea, and an increased risk of infection.

In most cases, side effects go away on their own when the treatment is over.

Chemotherapy to treat uterine cancer can have additional side effects: early menopause and an inability to become pregnant.

Some chemo drugs can also cause kidney damage and hearing loss.

  • Hormone Therapy

Hormone therapy is sometimes appropriate to slow the growth of some types of endometrial cancer cells with hormone receptors on them.

Tumors that usually respond to hormone therapy include grade 1 or 2 tumors and adenocarcinomas.

In the case of uterine cancer, hormone therapy usually requires large doses of progesterone in pill form.

As with other treatment options, there are side effects with hormone therapy that may include weight gain, muscle aches, increased appetite, fluid retention, and insomnia.

 

Coping and Support

Coping with a cancer diagnosis and treatment can be challenging.

Along with physical effects, you will likely experience a range of social, emotional, and financial effects of a diagnosis.

Your team of medical experts will help you understand what to expect during every stage of treatment and offer resources for coping and getting the support you need.

Many people facing uterine cancer feel afraid of the side effects of treatment.

Your health care team will work with you to prevent and relieve side effects through palliative care.

You may also find yourself struggling with the social and emotional effects of difficult emotions like rage, anxiety, and stress.

While you may have trouble communicating how you feel and what you need from friends and family, they will also probably be unsure of what to say and how they can help.

Patients and family members are encouraged to share their feelings with the health care team and look for a support group in the area for help.

Counseling can be an effective way to deal with your mixed emotions and struggles.

Oncology social workers can help with the practical and emotional challenges of dealing with a uterine cancer diagnosis.

An oncology social worker can help with the psychosocial problems you face during your treatment, including difficulty adjusting to being ill, isolation from friends and family, difficulty making treatment decisions, changes in how you feel about yourself, caregiver issues, cultural concerns you may have, and planning for end-of-life issues.

In many cases, a social worker will serve as the first support person you work with, although he or she may refer you to someone else.

If your social worker is unable to provide the level of help you need, you may be referred to family and patient counseling or psychotherapy.

You may also find pastoral services helpful.

Many clergies today have pastoral training for working with people with cancer.

Cancer is not always something that can be treated or cured.

For some people, cancer is a chronic illness that needs to be managed.

In these cases, cancer may be controlled with treatments that stop it from spreading, and sometimes treatments can shrink cancer and give you a break until it grows again.

Living with chronic or recurring cancer can mean living with uncertainty, but it can help to stay informed, express your feelings, and find ways to relax.

A counselor or support group can help you manage the sense of loss and grief you may find yourself feeling when living with cancer means learning a new normal.

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