Definition: Uterine cancer (endometrial cancer) is a tumor that develops in the body of the uterus (uterine corpus).

It occurs when cells in some part of the uterus divide and reproduce uncontrollably until a cancerous (malignant) lesion or tumor is formed.

Endometrial carcinoma- when the cancer arises from the lining of the uterus (endometrium) Uterine sarcoma- when the cancer arises in the muscle or other supporting tissues of the uterus (fatty tissue, bone, or fibrous tissue) Additional information: Endometrial cancer is the most common cancer found in the female pelvis; it occurs more than twice as often as cervical cancer. Endometrial cancer occurs more frequent in older women (peak age of 55 to 65 years), with only a 2% to 5% incidence among women younger than 40 years of age. Female patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome have a 60% lifetime risk of uterine cancer. Pregnancy reduces uterine cancer risk; there is a 30% risk reduction with the first pregnancy and 25% reduction with each subsequent pregnancy. Etiology: Common stimulus for uterine cancer development Unopposed oestrogen exposure Endogenous or exogenous

Oestrogen exposure - carcinogenic by causing endometrial hyperplasia, metaplasia and subsequent dysplasia. Non-oestrogen dependent phenotype exits and is characterize by a multiparous, thin woman with poorly differentiated histology and a worse prognosis. Risk Factors: Endogenous oestrogen excess Older age Early menarche Late menopause Low parity

Anovulatory cycles Obesity Insulin resistance/diabetes

Exogenous oestrogen exposure Others Hormone-secreting ovarian cancer granulosa cell tumour theca cell tumour Hereditary non-polyposis colorectal cancer Tamoxifen Hormone replacement therapy Isoflavones- soya, grains, seeds

Reference: Oncoly by Orla McArdle and Deirdre OMahony, 2008 pages 1075-1077
Stage and Grade of Endometrial Cancer The American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics staging classification: TX. Primary tumor cannot be assessed. T0. No primary tumor is seen. Tis (Carcinoma in situ). The cancer is found only in one area of the uterus and only in a few layers of cells. T1 (Stage I). Tumor is contained in the uterus. It has not spread to the cervix. T1a (Stage IA). Tumor is in the lining of the uterus (endometrium) or has spread into less than one-half of the muscle tissue (myometrium) of the uterus. T1b (Stage IB). Tumor has spread to one-half or more of the myometrium. T2 (Stage II). Tumor has spread from the uterus to the cervix but has not spread outside the uterus. T3a (Stage IIIA). Tumor is on the outer surface of the uterus, or in the ovaries or fallopian tubes. T3b (Stage IIIB). Tumor has spread (metastasized) into the tissue layers of thevagina. T4 (Stage IVA). Tumor has spread into the bladder or rectum. The TNM system stages lymph node involvement (N) to help determine the treatment options at each stage. NX. Lymph nodes near the primary tumor cannot be evaluated. N0. Cancer has not spread to lymph nodes near the primary tumor. N1 (IIIC1). Cancer has spread to lymph nodes near the primary tumor. N2 (IIIC2). Cancer has spread to the lymph nodes near the aorta, with or without spreading to the pelvic lymph nodes.

The TNM system stages metastasis (M) in the following way: M0. No distant metastasis is found. M1 (IVB). Metastasis to another area of the body has occurred, but not to the vagina, to the pelvic membranes and adjoining tissue, or to the lymph nodes near the aorta. The FIGO stages and the AJCC TNM class are grouped in the following table. Classification of endometrial cancer FIGO stage Stage 0 Stage I Stage IA Stage IB Stage II Stage III Stage IIIA Stage IIIB Stage IIIC1 Stage IIIC2 Stage IVA Stage IVB Tis, N0, M0 T1, N0, M0 T1a, N0, M0 T1b, N0, M0 T2, N0, M0 T3, N0, M0 T3a, N0, M0 T3b, N0, M0 T1-T3, N1, M0 T1-T3, N2, M0 T4, any N, M0 Any T, any N, M1 TNM class

Grade of endometrial cancer The grade of endometrial cancer refers to how the cancer cells look under a microscope. Knowing the grade can help your doctor decide which treatment options are best for you. Endometrial cancer cells are described as well-differentiated, moderately differentiated, or poorly differentiated. Differentiation is a term used to describe how clearly the cancer cells can be distinguished from the surrounding normal tissues and how normal or abnormal the cells look. GX. Grade cannot be assessed G1: Well-differentiated G2: Moderately differentiated G3-G4: Poorly differentiated or undifferentiated

PATHOPHYSIOLOGY

Screening:
Tests that may detect (find) endometrial cancer Pap test

A Pap test or pap smear is a procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, a brush, or a small wooden stick is used to gently scrape cells from the cervix and vagina. The cells are viewed under a microscope to find out if they are abnormal. Pap tests are not used to screen for endometrial cancer; however, Pap test results sometimes show signs of an abnormal endometrium (lining of the uterus). Follow-up tests may detect endometrial cancer.

Transvaginal ultrasound or endovaginal ultrasound

Transvaginal ultrasound (TVU) is a procedure used to examine the vagina, uterus, fallopian tubes, and bladder. An ultrasound transducer (probe) is inserted into the vagina and used to bounce highenergy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The doctor can identify tumors by looking at the sonogram

Additional info: No studies have shown that screening by transvaginal ultrasound (TVU) lowers the number of deaths caused by endometrial cancer.

Transvaginal ultrasound. An ultrasound probe connected to a computer is inserted into the vagina and is gently moved to show different organs. The probe bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).

TVU is commonly used to examine women who have abnormal vaginal bleeding. For women who have or are at risk for hereditary non-polyposis colon cancer, experts suggest yearly screening with transvaginal ultrasound, beginning as early as age 25.

Endometrial sampling
Endometrial sampling is the removal of tissue from the endometrium by inserting a brush, curette, or thin, flexible tube through the cervix and into the uterus. The tool is used to gently scrape a small amount of tissue from the endometrium and then remove the tissue samples. A pathologist views the tissue under a microscope to look for cancer cells. Endometrial sampling is commonly used to examine women who have abnormal vaginal bleeding. If you have abnormal vaginal bleeding, check with your doctor.

Cure or Treatment
Uterine cancer is treated by one or a combination of treatments, including surgery, radiation therapy, chemotherapy, and hormone therapy.

Surgery
-is the removal of the tumor and surrounding tissue during an operation. -First treatment used for uterine cancer.

1. Simple hysterectomy - removal of the body of the uterus and cervix 2. Radical hysterectomy - removal of the uterus, cervix, the upper part of the vagina, and nearby tissues - In this operation, the entire uterus, the tissues next to the uterus (parametrium and uterosacral ligaments), and the upper part of the vagina (next to the cervix) are all removed. 3. Bilateral salpingo-oophorectomy - This operation removes both fallopian tubes and both ovaries. - usually done at the same time the uterus is removed (either by simple hysterectomy or radical hysterectomy) to treat endometrial cancers. Removing both ovaries means that you will go into menopause if you have not done so already.

Hysterectomy may be performed as a traditional surgery (with one large incision) or by laparoscopy, which uses several smaller incisions. a camera and instruments are inserted through small, keyhole incisions. The surgeon then directs the robotic instruments to remove the uterus, cervix, and surrounding tissue.

Radiation therapy
is the use of high-energy x-rays or other particles to kill cancer cells. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time. 1. External-beam radiation therapy - The most common type of radiation treatment which is radiation given from a machine outside the body. 2. Internal radiation therapy or brachytherapy - When radiation treatment is given using implants - By injecting a small amount of radioactive material directly into the tumor.

Side effects from radiation therapy: Fatigue mild skin reactions upset stomach loose bowel movements

Additional: Advise patients not to have sexual intercourse during radiation therapy. Women may resume normal sexual activity within a few weeks after treatment if they feel ready.

Chemotherapy
is the use of drugs to kill cancer cells, usually by stopping the cancer cells ability to grow and divide. Systemic chemotherapy is delivered through the bloodstream to reach cancer cells throughout the body. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Chemotherapy may be used:

as the primary treatment for recurrent uterine cancer to destroy cancer cells after surgery to destroy cancer cells left behind and to reduce the risk of the cancer recurring (adjuvant chemotherapy) to relieve pain or to control the symptoms of advanced uterine cancer (palliative chemotherapy) Endometrial carcinoma The most common chemotherapy drugs used to treat endometrial carcinoma are:

doxorubicin (Adriamycin) cisplatin (Platinol AQ) carboplatin (Paraplatin, Paraplatin AQ) ifosfamide (Ifex) paclitaxel (Taxol) docetaxel (Taxotere) The most common chemotherapy combinations used to treat endometrial carcinoma are:

cisplatin and doxorubicin paclitaxel and doxorubicin carboplatin and docetaxel carboplatin and paclitaxel cisplatin, paclitaxel and doxorubicin Carcinosarcoma may be treated with cisplatin and ifosfamide, with or without paclitaxel.

Uterine sarcoma The most common chemotherapy drugs used to treat uterine sarcoma are:

doxorubicin ifosfamide cisplatin paclitaxel docetaxel gemcitabine (Gemzar) The most common chemotherapy combinations used to treat uterine sarcoma are:

cisplatin and doxorubicin doxorubicin and ifosfamide docetaxel and gemcitabine Goal of Chemotherapy Is to destroy cancer remaining after surgery, slow the tumor's growth, or reduce side effects. Although chemotherapy can be given orally (by mouth), most drugs used to treat uterine cancer are given intravenously (IV). IV chemotherapy is either injected directly into a vein or through a catheter (a thin tube inserted into a vein). Side effects chemotherapy: Fatigue risk of infection nausea and vomiting loss of appetite Diarrhea Inability to become pregnant Early menopause. Hearing loss Kidney damage

Hormone therapy
is used to slow the growth of uterine cancer cells involves the sex hormone progesterone, given in a pill form Other hormone therapies: tamoxifen (Nolvadex) aromatase inhibitors (AIs) such as anastrozole (Arimidex) letrozole (Femara) exemestane (Aromasin).

An AI is a drug that reduces the amount of the hormone estrogen in a woman's body by stopping tissues and organs other than the ovaries from producing it. Side effects of hormone therapy: fluid retention increase in appetite Weight gain. Women in their childbearing years may have changes in their menstrual cycle.

Treatment options by stage

Stage I SurgerySurgery and radiation therapy Hormone therapy Surgery, radiation, and chemotherapy Stage II Surgery and radiation therapy Surgery, radiation, and chemotherapy Stage III Surgery and radiation therapy Surgery and chemotherapy Surgery, radiation, and chemotherapy Stage IV Surgery Radiation therapy Hormone therapy Chemotherapy Stage-adjusted survival rates 5-year survival >75% 60% 30% 10%

Stage I II III IV