Endometrial cancer

Overview

Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination or sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

Symptoms

These and other symptoms may be caused by endometrial cancer. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur: 

  •  Bleeding or discharge not related to menstruation (periods)
  •  Difficult or painful urination
  •  Pain during sexual intercourse
  •  Pain in the pelvic area.
  •  vaginal bleeding after menopause
  •  abnormal, watery, or blood-tinged discharge from vagina

 

Causes

Some risk factors associated with endometrial cancer include: 

Changes in the balance of female hormones in the body 

Fluctuations of the main hormones estrogen and progesterone can cause changes in the endometrium. 

A disease that increases the amount of estrogen but not the amount of progesterone in your body can put you at a greater risk or endometrial cancer. Some examples of such diseases are: irregular ovulation patterns, such as those experienced by women with poly-cystic ovary syndrome (PCOS), obesity, and diabetes. Taking hormones after menopause that contain estrogen but not progesterone can increase risk of endometrial cancer. 

A rare type of ovarian tumor that secretes estrogen can also increase the risk of endometrial cancer. 

More years of menstruation

Women who have started menstruation early (typically before the age of 12) or beginning menopause later increases the risk of endometrial cancer. The more periods had, the more exposure the endometrium has to estrogen. 

No pregnancies

Women who have never been pregnant are at a higher risk of endometrial cancer compared with those who have had at least one pregnancy. 

Older Age

The risk of endometrial cancer increases with age. The majority of endometrial cancers occurs in older women who have undergone menopause. 

Obesity

Excess body fat alters the bodys balance of hormones. Women who are obese are at a higher risk of endometrial cancer. 

Hormone Therapy for Breast Cancer 

Women who have undergone hormone therapy with the drug tamoxifen have an increased risk of endometrial cancer. For most women, the small risk of endometrial cancer does not outweigh the benefits of tamoxifen.

Inherited colon cancer syndrome

Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome that increases the risk of colon cancer and other cancers, including endometrial cancer. 

http://www.mayoclinic.com

Prevention

All women should have regular pelvic exams beginning at the onset of sexual activity (or at the age of 21 if not sexually active) to help detect signs of infection of abnormal development. Women should have a Pap smears beginning 3 years after becoming sexually active. Women with any risk factors for endometrial cancer should be followed more closely by their doctors. Frequent pelvic examinations and screening tests such as a Pap smear and endometrial biopsy should be considered. Women who are taking estrogen replacement therapy should have regular pelvic examinations and Pap smears.

Diagnosis

Diagnosis of endometrial cancer is made first by a physical examination and dilation and curettage (removal of endometrial tissue; D&C). This tissue is then examined histologically for characteristics of cancer. If cancer is found, medical imaging may be done to see whether the cancer has spread or invaded tissue.

Examination

Routine screening of asymptomatic people is not indicated, since the disease is highly curable in its early, symptomatic stages. Instead, women, particularly menopausal women, should be aware of the symptoms and risk factors of endometrial cancer. A cervical screening test, such as a Pap smear, is not a useful diagnostic tool for endometrial cancer because the smear will be normal 50% of the time. A Pap smear can detect disease that has spread to the cervix.[5] Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced. Cervical stenosis, the narrowing of the cervical opening, is a sign of endometrial cancer when pus or blood is found collected in the uterus (pyometra or hematometra).

Women with Lynch syndrome should begin to have annual biopsy screening at the age of 35. Some women with Lynch syndrome elect to have a prophylactic hysterectomy and salpingo-oophorectomy to greatly reduce the risk of endometrial and ovarian cancer.

Transvaginal ultrasound to examine the endometrial thickness in women with postmenopausal bleeding is increasingly being used to aid in the diagnosis of endometrial cancer in the United States. In the United Kingdom, both an endometrial biopsy and a transvaginal ultrasound used in conjunction are the standard of care for diagnosing endometrial cancer. The homogeneity of the tissue visible on transvaginal ultrasound can help to indicate whether the thickness is cancerous. Ultrasound findings alone are not conclusive in cases of endometrial cancer, so another screening method (for example endometrial biopsy) must be used in conjunction. Other imaging studies are of limited use. CT scans are used for preoperative imaging of tumors that appear advanced on physical exam or have a high-risk subtype (at high risk of metastasis). They can also be used to investigate extrapelvic disease. An MRI can be of some use in determining if the cancer has spread to the cervix or if it is an endocervical adenocarcinoma. MRI is also useful for examining the nearby lymph nodes.

Dilation and curettage or an endometrial biopsy are used to obtain a tissue sample for histological examination. Endometrial biopsy is the less invasive option, but it may not give conclusive results every time. Hysteroscopy only shows the gross anatomy of the endometrium, which is often not indicative of cancer, and is therefore not used, unless in conjunction with a biopsy. Hysteroscopy can be used to confirm a diagnosis of cancer. New evidence shows that D&C has a higher false negative rate than endometrial biopsy.

Before treatment is begun, several other investigations are recommended. These include a chest x-ray, liver function tests, kidney function tests, and a test for levels of CA-125, a tumor marker that can be elevated in endometrial cancer.

Prognosis

Survival rates

The five-year survival rate for endometrial adenocarcinoma following appropriate treatment is 80%. Most women, over 70%, have FIGO stage I cancer, which has the best prognosis. Stage III and especially Stage IV cancers has a worse prognosis, but these are relatively rare, occurring in only 13% of cases. The median survival time for stage III-IV endometrial cancer is nine to ten months. Older age indicates a worse prognosis. In the United States, white women have a higher survival rate than black women, who tend to develop more aggressive forms of the disease by the time of their diagnosis. Tumors with high progesterone receptor expression have a good prognosis compared to tumors with low progesterone receptor expression; 93% of women with high progesterone receptor disease survived to three years, compared with 36% of women with low progesterone receptor disease. Heart disease is the most common cause of death among those who survive endometrial cancer, with other obesity-related health problems also being common.

Reccurence rates

Recurrence of early stage endometrial cancer ranges from 3 to 17%, depending on primary and adjuvant treatment. Most recurrences (75–80%) occur outside of the pelvis, and most occur two to three years after treatment, 64% after two years and 87% after three years.

Higher-staged cancers are more likely to recur, as are those that have invaded the myometrium or cervix, or that have metastasized into the lymphatic system. Papillary serous carcinoma, clear cell carcinoma, and endometrioid carcinoma are the subtypes at the highest risk of recurrence. High-grade histological subtypes are also at elevated risk for recurrence.

The most common site of recurrence is in the vagina; vaginal relapses of endometrial cancer have the best prognosis. If relapse occurs from a cancer that has not been treated with radiation, EBRT is the first-line treatment and is often successful. If a cancer treated with radiation recurs, pelvic exenteration is the only option for curative treatment. Palliative chemotherapy, cytoreductive surgery, and radiation are also performed. Radiation therapy (VBT and EBRT) for a local vaginal recurrence has a 50% five-year survival rate. Pelvic recurrences are treated with surgery and radiation, and abdominal recurrences are treated with radiation and, if possible, chemotherapy. Other common recurrence sites are the pelvic lymph nodes, para-aortic lymph nodes, peritoneum (28% of recurrences), and lungs, though recurrences can also occur in the brain (<1%), liver (7%), adrenal glands (1%), bones (4–7%; typically the axial skeleton), lymph nodes outside the abdomen (0.4–1%), spleen, and muscle/soft tissue (2–6%).

Treatment

Surgery

The primary treatment for endometrial cancer is surgery; 90% of women with endometrial cancer are treated with some form of surgery.Surgical treatment typically consists of hysterectomy including a bilateral salpingo-oophorectomy, which is the removal of the uterus, and both ovaries and Fallopian tubes. Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is performed for tumors of histologic grade II or above. Lymphadenectomy is routinely performed for all stages of endometrial cancer in the United States, but in the United Kingdom, the lymph nodes are typically only removed with disease of stage II or greater. The topic of lymphadenectomy and what survival benefit it offers in stage I disease is still being debated. In stage III and IV cancers, cytoreductive surgery is the norm, and a biopsy of the omentum may also be included. In stage IV disease, where there are distant metastases, surgery can be used as part of palliative therapy. Laparotomy, an open-abdomen procedure, is the traditional surgical procedure; however, laparoscopy (keyhole surgery) is associated with lower operative morbidity. The two procedures have no difference in overall survival. Removal of the uterus via the abdomen is recommended over removal of the uterus via the vagina because it gives the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer. Staging of the cancer is done during the surgery.

The few contraindications to surgery include inoperable tumor, massive obesity, a particularly high-risk operation, or a desire to preserve fertility. These contraindications happen in about 5–10% of cases. Women who wish to preserve their fertility and have low-grade stage I cancer can be treated with progestins, with or without concurrent tamoxifen therapy. This therapy can be continued until the cancer does not respond to treatment or until childbearing is done. Uterine perforation may occur during a D&C or an endometrial biopsy. Side effects of surgery to remove endometrial cancer can specifically include sexual dysfunction, temporary incontinence, and lymphedema, along with more common side effects of any surgery, including constipation.

Add-on therapy

There are a number of possible additional therapies. Surgery can be followed by radiation therapy and/or chemotherapy in cases of high-risk or high-grade cancers. This is called adjuvant therapy.

Chemotherapy:

Adjuvant chemotherapy is a recent innovation, consisting of some combination of paclitaxel (or other taxanes like docetaxel), doxorubicin (and other anthracyclines), and platins (particularly cisplatin and carboplatin). Adjuvant chemotherapy has been found to increase survival in stage III and IV cancer more than added radiotherapy. Mutations in mismatch repair genes, like those found in Lynch syndrome, can lead to resistance against platins, meaning that chemotherapy with platins is ineffective in people with these mutations. Side effects of chemotherapy are common. These include hair loss, low neutrophil levels in the blood, and gastrointestinal problems.

In cases where surgery is not indicated, palliative chemotherapy is an option; higher-dose chemotherapy is associated with longer survival.[ Palliative chemotherapy, particularly using capecitabine and gemcitabine, is also often used to treat recurrent endometrial cancer.

Radiotherapy:

Adjuvant radiotherapy is commonly used in early-stage (stage I or II) endometrial cancer. It can be delivered through vaginal brachytherapy (VBT), which is becoming the preferred route due to its reduced toxicity, or external beam radiotherapy (EBRT). Brachytherapy involves placing a radiation source in the organ affected; in the case of endometrial cancer a radiation source is placed directly in the vagina. External beam radiotherapy involves a beam of radiation aimed at the affected area from outside the body. VBT is used to treat any remaining cancer solely in the vagina, whereas EBRT can be used to treat remaining cancer elsewhere in the pelvis following surgery. However, the benefits of adjuvant radiotherapy are controversial. Though EBRT significantly reduces the rate of relapse in the pelvis, overall survival and metastasis rates are not improved. VBT provides a better quality of life than EBRT.

Radiotherapy can also be used before surgery in certain cases. When pre-operative imaging or clinical evaluation shows tumor invading the cervix, radiation can be given before a total hysterectomy is performed. Brachytherapy and EBRT can also be used, singly or in combination, when there is a contraindication for hysterectomy. Both delivery methods of radiotherapy are associated with side effects, particularly in the gastrointestinal tract.

Hormonal therapy:

Hormonal therapy is only beneficial in certain types of endometrial cancer. It was once thought to be beneficial in most cases. If a tumor is well-differentiated and known to have progesterone and estrogen receptors, progestins may be used in treatment. About 25% of metastatic endometrioid cancers show a response to progestins. Also, endometrial stromal sarcomas can be treated with hormonal agents, including tamoxifen, 17-hydroxyprogesterone caproate, letrozole, megestrol acetate, and medroxyprogesterone. This treatment is effective in endometrial stromal sarcomas because they typically have estrogen and/or progestin receptors. Progestin receptors function as tumor suppressors in endometrial cancer cells. Preliminary research and clinical trials have shown these treatments to have a high rate of response even in metastatic disease.

Monitoring

The tumor marker CA-125 is frequently elevated in endometrial cancer and can be used to monitor response to treatment, particularly in serous cell cancer or advanced disease. Periodic MRIs or CT scans may be recommended in advanced disease and women with a history of endometrial cancer should receive more frequent pelvic examinations for the five years following treatment. Examinations conducted every three to four months are recommended for the first two years following treatment, and every six months for the next three years.

Women with endometrial cancer should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival, and because it has its own costs and side effects. If a recurrence is suspected, PET/CT scanning is recommended.