The uterus is a part of the female reproductive system responsible for the growth and development of the fetus. The inner lining of the uterus is the endometrium.
Endometrial cancer, or endometrial carcinoma, occurs when the endometrium cells start to grow and multiply uncontrollably. It is one of the most common cancers affecting the female reproductive system. It is a type of uterine cancer. The other type is uterine sarcoma, which involves the muscles and connective tissues of the uterus.
Unlike most cancers, the diagnosis of endometrial (uterine) cancer occurs early due to the presentation of symptoms. Thus, the treatment and prognosis of endometrial carcinoma are favorable. Endometrial adenocarcinomas constitute about 80% of all endometrial cancers in the endometrial glands.
Endometrial cancer is one of the most common cancers in women, and the number of cases is increasing. The data from the World Health Organization in 2020 reported endometrial cancer as the 6th most common cancer in women, ranking endometrial carcinoma at 15th among overall cancers.
There is also an increased incidence of this cancer type in India. This rise in endometrial carcinoma in India is attributed to changing trends in the reproductive profile and lifestyle of women in India, particularly in urban areas.
Based on the type of cell type from which it originates, endometrial carcinoma is classified into various types. The following are the different types of endometrial cancer are:
The most common types of endometrial cancer are:
It is one of the most common endometrial cancers and constitutes about 85–90% of the cases. The condition usually affects women between the ages of 55 and 65. It is also called the type 1 uterine carcinoma. It has a slow progression rate. Patients with endometrial adenocarcinoma have a relatively favorable prognosis.
Previously called malignant mixed Müllerian tumors, uterine carcinosarcomas are rare and highly aggressive tumors. Uterine carcinosarcoma has a low survival rate, with a 5-year survival rate of 38%. When histologically examined, these tumors have the features of both sarcoma and carcinoma.
It is one of the endometrial cancer types, and it accounts for only 5% of all endometrial cases. It has a variable degree of differentiation.
It is an aggressive cancer similar to the small-cell cancer of the lungs. Patients with this condition experience abdominal pain and abnormal vaginal bleeding.
Transitional cell carcinoma is one of the variants of endometrial carcinoma and has distinctive immunophenotypic and histological features. It is a rare occurrence.
The condition is characterized by abnormal p53 staining in immunohistochemistry, accounting for almost 20% of endometrial carcinomas. However, the mortality rate for serous carcinoma is high, standing at 74%.
The following are the less common endometrial cancer types:
It is one of the rare and aggressive endometrial cancer types. Approximately 45% of the cases have extrauterine growth at diagnosis.
It is a rare type of endometrial cancer. There is a challenge in diagnosing this condition due to the varied morphology of the endometrium.
Endometrial cancer staging is a significant step in endometrial cancer management. Staging helps the specialist in assessing the extent of the disease’s spread. Determining the stage of endometrial carcinoma plays a pivotal role in devising a customized treatment plan and effectively managing the disease.
Stage 1 endometrial cancer is divided into stage 1A and stage 1B.
During stage 1A, the cancer is present in the inner uterine lining and has invaded less than half of the uterine muscle layer.
During stage 1B, the cancer has spread over half of the myometrium (uterine muscles) but has not invaded beyond the uterine body. The cancer at stage 1 does not spread to the lymph nodes or distant organs.
In stage 2, cancer of the endometrium has spread to the uterine body and invaded the supporting cervical connective tissue (cervical stroma). However, the cancer has not spread outside the uterus, to the lymph nodes and distant organs.
Stage 3 endometrial cancer is subdivided into 3A, 3B, 3C1, and 3C2.
Stage 3A is characterized by the spread of cancer to the outer uterine surface and/or to the ovaries or the fallopian tubes.
Stage 3B involves spreading the malignant cells to the vagina or the tissues surrounding the uterus (parametrium).
Stage 3C1 involves the growth of tumors in the uterine body and some surrounding tissues. However, it does not invade the rectum or bladder. The cancer may invade pelvic lymph nodes but not aortic lymph nodes.
Stage 3C2 involves the growth of the cancer into the uterine body. It has not grown into the rectum or bladder. The cancer has spread to the aortic lymph nodes. Stage 3 endometrial cancer does not spread to distant sites.
Stage four endometrial cancer is divided into stages 4A and 4B.
In the 4A stage, the cancer invades the inner lining of the urinary bladder of the rectum. The cancer may have spread to the nearby lymph nodes but not to the distant organs.
In the 4B stage, the cancer has spread to the omentum, upper abdomen, groin lymph nodes, or distant organs, such as the lungs, liver, or bones. The cancer may or may not spread to the other lymph nodes.
In most cases, women experience endometrial cancer symptoms in the early stages. Therefore, it is easy to catch this cancer in its early stages and receive appropriate treatment.
Endometrial cancer may occur in any woman, with or without the underlying known risk factors. However, some women are more vulnerable to developing endometrial cancer, such as women with higher levels of estrogen, early menstruation, and late menopause, older age, underlying medical conditions such as Lynch syndrome and obesity, those who have never been pregnant, and those who have received hormone therapy for breast cancer.
The most commonly observed endometrial cancer symptoms include:
Patients with endometrial cancer may experience pelvic pain if the tumor becomes large and starts exerting pressure on the surrounding structures and nerves. Patients may have discomfort in the abdomen when the spread of cancer results in fluid accumulation in the abdominal area. Pain may also develop when the tumor spreads to the abdomen and pelvis.
Pain during sexual intercourse is one of the endometrial cancer symptoms. It may also be caused due to sexual changes that result in vaginal dryness. Although it may occur due to age and other underlying medical conditions, such as endometriosis and uterine fibroids, it is important to rule out the presence of serious conditions.
Watery or bloody vaginal discharges should not be ignored as they could indicate endometrial cancer. The women should also consult the gynecologists if discharge occurs between periods and after sexual intercourse. Burning sensations and itching during discharge are usually due to a yeast infection. However, it should be examined by the doctor.
Menstrual bleeding, which is longer or heavier than usual, especially in women over 40, maybe a sign of endometrial cancer. A menstrual cycle shorter than 21 days is also a red flag for serious conditions.
Like other cancers, unexplained weight loss is also one of the endometrial cancer symptoms. There are several mechanisms through which endometrial cancer causes weight loss.
First, as the cancer cells require more energy to divide and proliferate, they receive more nutrition. Second, in the case of endometrial cancer, it spreads to the abdomen, pushes the stomach, and reduces its size. Third, patients with advanced cancer have widespread inflammation that disrupts the metabolic processes.
Irregular and heavy vaginal bleeding in patients with endometrial cancer may result in anemia. Patients with anemia may experience fatigue, weakness, chest pain, shortness of breath, and dizziness.
Bloating may be one of the advanced-stage endometrial cancer symptoms. It is due to the accumulation of fluid in the abdomen. It may also occur due to the significant growth of tumors.
Constipation and other gastrointestinal conditions, such as abdominal pain and diarrhea, could also appear as advanced-stage endometrial cancer symptoms. It occurs when the tumor spreads to the pelvis and the abdomen.
Symptoms of different types of endometrial (uterine) cancer are:
The most common endometrial adenocarcinoma symptoms include abnormal vaginal bleeding, pain during sexual intercourse, watery discharge, and pelvic and abdominal pain.
The most common uterine papillary serous carcinoma symptoms include post-menopausal bleeding, pelvic pain, pain during sexual intercourse, and unexplained weight loss.
The most common uterine clear cell carcinoma symptom is abnormal vaginal discharge or bleeding. The other common symptoms include loss of appetite, bloating, weight loss, and altered bowel or bladder habits.
The common symptoms of uterine carcinosarcoma include vaginal bleeding, abdominal or pelvic pain, and distension.
Some of the possible endometrial cancer causes include:
Certain medical conditions, such as obesity, irregular ovulation, and diabetes, increase the level of estrogen. Exposure to estrogen may also be due to estrogen-based hormone therapy. Higher than normal levels of estrogen can lead to excessive growth of endometrial cells, which may eventually lead to cancer.
Women who consume a diet rich in animal fats, total fat, and saturated fat may develop endometrial cancer.
Studies have reported an association between the age of menopause and endometrial cancer. Having a late menopause may be one possible endometrial cancer causes.
Excessive exposure to estrogen may cause endometrial cancer. When the woman gets pregnant, the exposure to estrogen is interrupted, which helps reduce the risk of endometrial cancer. Thus, women who never attain pregnancy may be at a higher risk of developing endometrial cancer.
Obesity is also one of the possible endometrial cancer causes. Obese women may be exposed to estrogen or have an imbalance in their hormone levels and may develop endometrial cancer.
Women of older age may develop endometrial cancer. Endometrial cancer generally occurs after menopause.
Resistance to insulin in patients with diabetes may also lead to endometrial cancer. Further, insulin resistance also results in hormonal imbalances in women.
Women with a family history of endometrial or colorectal cancer may have a higher risk of developing endometrial cancer.
Women with a history of undergoing radiation therapy to manage pelvic cancer may also develop endometrial cancer due to radiation-induced mutations in the endometrial cells.
Women with underlying medical conditions, such as Lynch syndrome, may also develop endometrial cancer.
It is important to consult an oncologist if symptoms like painful intercourse, unexplained weight loss, loss of appetite, irregular vaginal bleeding, bleeding between periods, bleeding after menopause, and gastrointestinal issues are observed persistently. It is important to note that other gynecological cancers also show similar symptoms, and therefore, a proper evaluation helps in arriving at a conclusive diagnosis.
Endometrial cancer needs a comprehensive care approach. Once the diagnosis is confirmed, specialists perform staging, which helps in determining the extent of the disease’s spread.
Once the stage is confirmed, specialists devise an individualized treatment plan. Along with the stage, the type of endometrial cancer, its exact location, its grade, the patient’s age, their overall health condition, and their preferences are considered while the treatment plan is made.
Endometrial cancer diagnosis can be done through the following methods:
Several symptoms of endometrial cancer overlap with certain other conditions. Thus, it is important to rule out more serious conditions. The doctor may ask the patients about their medical history. Patients with Lynch syndrome, obesity, hereditary nonpolyposis colorectal cancer, and ovarian diseases have an increased risk of developing endometrial cancer. Further, hormone therapy for managing ovarian cancer also increases the risk of endometrial cancer.
The patients may also undergo a detailed pelvic examination. Pelvic examinations should be done regularly, especially in women with an increased risk for endometrial or vaginal cancer. During a pelvic examination, the doctor evaluates the external genitals. In addition, gloved fingers are inserted into the vagina to detect any tumor or abnormal growth. The signs of abnormalities or cancer can also be detected by inserting the speculum into the vagina, which improves the internal view.
Although a Pap smear does not diagnose endometrial cancer, it helps to detect cell changes that suggest a possibility of precancerous or cancerous conditions. It also helps diagnose non-cancerous conditions, such as inflammation or infection, which may also be the reasons for symptoms. Pathologists collect the cells from the uterine opening (cervix) during a Pap smear. The collected cells are examined under the microscope to detect abnormal cells.
The endometrial biopsy test is an accurate tool for diagnosing endometrial cancer. During a biopsy, samples of the abnormal cells or tissues are obtained and examined under the microscope to detect morphological changes. Endometrial biopsy is one of the most common methods to obtain endometrial tissue samples. It involves the use of a thin tube, which is inserted into the uterus. Suction is applied through the tube to collect the samples.
Hysteroscopy, an endometrial cancer test, is performed with the help of a hysteroscope. A hysteroscope is a flexible, thin tube inserted into the uterus through the vagina and cervix. The hysteroscope has a camera at the tip that transmits images of the internal tissues of the endometrium and the uterus. This procedure can help in the collection of a biopsy sample.
D&C is performed when the doctor cannot obtain enough abnormal tissues for examination during an endometrial biopsy. It is also done when there is a suspicion of endometrial cancer, but the results are not confirmatory. The procedure is done under sedation or general anesthesia. During the procedure, the cervix of the patient is dilated, and the uterine tissues are scrapped with an instrument. The procedure may or may not involve the use of hysteroscopy.
Ultrasound is usually the initial imaging method used to evaluate the uterus, ovary, and fallopian tubes in women suspected of having gynecological issues.
Ultrasound, as an endometrial cancer radiology technique, uses sound waves to create images. Several types of ultrasound procedures are performed. These include transvaginal ultrasound and pelvic ultrasound. Transvaginal ultrasound provides better images of the uterus compared to pelvic ultrasound. To view the endometrial cancer on ultrasound more clearly, the doctor may also recommend a hysterosonogram or saline infusion sonogram. It involves infusing salt water into the uterus before an ultrasound.
An MRI scan plays an important role in assessing endometrial cancer. An MRI scan helps evaluate the depth of tumor invasion into the myometrium, which correlates with lymph node metastasis and tumor grade. It helps in staging the disease and determining the disease prognosis. MRI also assists in planning radiation ports, evaluating treatment responses, and surveillance after treatment.
Proctoscopy and cystoscopy are performed when there is a suspicion of cancer being spread to the rectum or bladder. Proctoscopy is performed by inserting a tube into the rectum, while cystoscopy involves the insertion of a tube into the bladder. Both procedures are performed under local anesthesia. Sometimes, the doctor may also obtain sample tissues for further examination.
A CT scan cannot accurately diagnose endometrial cancer due to its poor soft tissue differentiation. The images obtained with a CT scan are less specific and sensitive in detecting myometrium invasion and cervix involvement than those obtained with an MRI. However, a CT scan may be used to detect the spread of cancer to other sites and the recurrence of cancer.
A PET scan is a powerful imaging technique to detect cancer cells throughout the body. It uses radioactive glucose derivatives. Due to their high metabolism, once the radioactive glucose enters the body, the cancer cells collect the substances in them. The scanner scans the body and detects the sites where the radioactive sugar is collected; these sites appear as bright spots. PET scans help in staging the disease by determining the extent of the disease.
Blood tests do not confirm the presence of cancer. However, they provide vital information about the overall body's health. Bleeding due to endometrial cancer may indicate anemia in blood tests. The doctor may also advise the patients to test for CA-125, which is a blood marker for endometrial cancer.
A chest X-ray may also be recommended in patients experiencing lung-related symptoms, such as shortness of breath or blood in mucus, which indicates that the cancer may have spread to the lungs.
A bone scan is recommended for patients suspected of having cancer metastasis in the bones.
No two endometrial cancer cases are the same, and therefore, it is necessary to devise a personalized treatment plan. Customized treatment plans help improve the clinical outcomes and the overall disease prognosis. The following are the commonly recommended endometrial cancer treatment options:
Surgery is recommended as a primary endometrioid carcinoma treatment. The type of surgery depends on the stage of the disease. For early-stage endometrial cancers, surgery may be the only treatment required. However, for patients with advanced-stage cancer, multimodal or combination treatment is recommended.
Hysterectomy, an endometrial cancer surgery, is the process of removing the cervix and uterus. A hysterectomy performed through the abdomen is known as an abdominal or simple hysterectomy. When the uterus is removed via the vagina, it is known as a vaginal hysterectomy. In some cases, the doctors may also remove the ovaries and/or fallopian tubes along with the uterus.
The doctor removes the lymph nodes of the pelvis to determine the presence of cancer cells in the lymph nodes. This procedure is known as lymph node dissection. The doctor may also perform sentinel lymph node mapping to determine which lymph node would be first affected by the cancer.
Apart from the abdominal hysterectomy, minimally invasive surgery may also be performed to remove the cervix and uterus. The minimally invasive surgeries include laparoscopic surgery and robotic-assisted surgery. Laparoscopic surgery is performed through a laparoscope, while robotic-assisted surgery is performed on a robotic surgery platform wherein robotic arms that are controlled by a robotic surgeon perform the surgery.
It is generally used in combination with surgery or chemotherapy as a part of endometrial adenocarcinoma treatment. Radiation therapy can be delivered through two techniques, namely external beam radiotherapy and internal beam radiotherapy (brachytherapy). In some cases, both procedures are used. Vaginal brachytherapy may be done after a hysterectomy. Brachytherapy may be administered at a high-dose or low-dose rate.
Chemotherapy is an endometrial cancer therapy wherein specific anti-cancer medications are used to kill or prevent the growth of cancer cells. These endometrial cancer medications are often recommended for aggressive and advanced-stage endometrial cancers.
Chemotherapy for endometrial cancer is usually administered in cycles, which include a treatment period followed by a rest period. Usually, the chemotherapy drugs are used in combinations. Sandwich therapy may also be used, including radiation therapy between the two cycles of chemotherapy drugs for endometrial cancer.
Endometrial cancer is hormone-sensitive, and therefore, hormone therapy may be recommended as a treatment option. Hormone therapy works by killing the cancer cells or slowing their growth. This form of endometrial cancer treatment involves the use of hormones or drugs that block the hormones. The therapy is usually used in patients with advanced endometrial cancer. The oncologists generally combine hormone therapy with chemotherapy to improve outcomes.
There are specific proteins and enzymes that regulate several vital cellular processes specific to cancer cells. As an endometrial cancer treatment, targeted therapy uses specific drugs that target these enzymes or proteins and interfere with these processes, thereby killing or preventing the growth of cancer cells. For instance, targeted therapy targets the proteins required to form new blood vessels and grow and divide cancer cells.
If the patients are not responding to any current treatments available, they are advised to enroll themselves in clinical trials related to endometrial cancer treatment and management. Clinical trials help cancer patients try new endometrial cancer drugs, treatment approaches or methods, etc., that may improve the survival rates and prognosis for these patients.
HCG Cancer Center is a leading cancer hospital in India with world-class facilities for diagnosing and managing endometrial cancer. The center has an excellent diagnostic infrastructure, comprising the most modern techniques for accurate diagnosis. The center has all the high-end endometrial cancer treatment facilities. The expert team at the center is extensively experienced in offering value-based and patient-centric care to patients diagnosed with endometrial cancer.
Those factors that increase the risk of developing endometrial cancer are referred to as endometrial cancer risk factors. Having these risk factors does not guarantee an endometrial cancer diagnosis; however, they increase one’s chances of developing this cancer.
Speaking of endometrial cancer prevention, it is not possible to prevent this cancer completely. However, making certain modifications to your lifestyle can help reduce the risk of endometrial cancer.
Endometrial cancer risk factors are categorized as modifiable or lifestyle-related factors and non-modifiable or non-lifestyle-related factors. Lifestyle-related factors are those that can be controlled and modified, and non-lifestyle-related factors are those that cannot be controlled. The most common endometrial cancer risk factors include:
Age is a non-modifiable risk factor for endometrial cancer. Endometrial cancer most commonly occurs in postmenopausal women and women over the age of 45. However, it may also occur in premenopausal women, especially when other risk factors, such as diabetes, obesity, and polycystic ovarian syndrome are associated.
Exposure to excess estrogen is also an endometrial adenocarcinoma risk factor. It may occur due to several underlying medical conditions, such as ovarian dysfunction and polycystic ovary syndrome. Women on estrogen-based hormone therapy also have a higher risk of developing endometrial cancer.
The uterus is exposed to estrogen during the menstrual cycle. In cases where the menstrual cycle starts early, and menopause is attained late, women have more number of menstrual cycles and therefore, higher exposure to estrogen. These women have a higher risk of developing endometrial cancer.
Women who have never attained pregnancy have a higher chance of getting endometrial cancer than women with at least one pregnancy. Getting pregnant reduces the period of uterine exposure to estrogen, thereby lowering the risk of endometrial cancer.
Some types of pelvic cancer require radiation therapy for their management. Radiation therapy uses high-energy radiation to kill cancer cells. However, in some cases, the healthy cells of the endometrium may also undergo mutations due to radiation therapy and may change into malignant cells.
Obesity is among the strongest risk factors for endometrial cancer. There are several mechanisms through which obesity causes endometrial cancer. Fat tissues may alter the levels of estrogen by converting androgens to estrogens, releasing excess estrogen into the bloodstream, and causing insulin resistance that can increase estrogen production.
It has been reported that overweight women have a two times higher risk and obese women have a three times higher risk of endometrial cancer than women with a healthy weight.
It is a condition characterized by the growth of endometrial tissues. Those with atypical hyperplasia have a higher risk of developing endometrial cancer. Studies have found that simple atypical hyperplasia progresses into endometrial cancer in about 8% of the cases, while complex atypical hyperplasia progresses into endometrial cancer in 29% of the cases.
Women with a family history of endometrial cancer may have an increased risk of developing this condition.
Tamoxifen is a medication used for the prevention and management of breast cancer. It mimics the action of estrogen on the uterine wall. In women with menopause, it stimulates the growth of the uterine lining, thereby increasing the risk of endometrial cancer. Although the risk of endometrial cancer with tamoxifen is low, women who are prescribed this drug should discuss this issue with their healthcare providers.
It is an inherited condition that increases the risk of several cancers, including endometrial cancer. It also enhances the risk of colon cancer. If a person has a family history of Lynch syndrome, the other family members should be screened for it and their risk of developing colon and endometrial cancers should be thoroughly assessed.
Women with diabetes have twice the risk of endometrial cancer than those without diabetes. Insulin resistance can cause increased estrogen levels, which is a risk factor for endometrial cancer.
It is not possible to prevent endometrial cancer as its exact cause is unknown. However, certain measures can help in reducing its risk. The following are the most important endometrial cancer prevention measures:
Maintaining a healthy weight significantly lowers the risk of endometrial cancer. Those women who are overweight or obese may consider losing weight and maintaining a healthy weight by reducing their calorie intake and enhancing their physical activity.
Opting for regular exercise can increase the chances of endometrial cancer prevention. Studies have reported that women who engage in regular physical activity have a 20–40% reduced risk of endometrial cancer.
Consuming a healthy diet comprising fruits and vegetables reduces the risk of endometrial cancer. Further, a diet that enhances obesity, such as a high-fat diet containing processed foods, should be avoided to lower the risk of endometrial cancer.
Limiting exposure to estrogen also lowers the risk of endometrial cancer. If the women are on hormone replacement therapy, they may discuss the risks and benefits of therapy with their healthcare providers. Further, estrogen-alone therapy may be replaced with a combination of estrogen-progestin therapy.
Several underlying medical conditions, such as obesity, diabetes, and polycystic ovarian syndrome, increase endometrial cancer risk. Managing these conditions lowers the risk of endometrial cancer.
Using birth control pills for at least one year may lower the risk of endometrial cancer. The reduction in risk may last for a few years after the drug is withdrawn. These drugs have side effects and should be taken after consultation with healthcare providers.
Getting pregnant at least once and breastfeeding lowers the risk of endometrial cancer due to reduced exposure to estrogen.
Regular check-ups for endometrial cancer may result in early diagnosis and management, especially in women with increased risk for hyperplasia and endometrial cancer.
Endometrial cancer initiates in the endometrium and is one of the most common cancers of the female reproductive system. The incidence of this cancer is rising in India. Some common types of endometrial carcinoma are endometrioid adenocarcinoma, small cell carcinoma, squamous cell carcinoma, uterine carcinosarcoma, serous carcinoma, and transitional carcinoma. Stage 1 refers to the early-stage, and stage 4 is the late-stage endometrial cancer.
