Uterine cancer

ALSO KNOWN AS: Endometrial carcinoma, cancer of the uterus, adenocarcinoma of the uterus, carcinosarcoma of the uterus, clear cell endometrial carcinoma, papillary serous carcinoma of the uterus, adenosquamous carcinoma of the uterus, endolymphatic stromal myosis, heterologous uterine sarcoma, homologous uterine sarcoma, leiomyosarcoma of the uterus, malignant mixed Mullerian tumor of the uterus, serous endometrial carcinoma, endometrial stromal sarcoma, rhabdosarcoma of the uterus, osteosarcoma of the uterus, chondrosarcoma of the uterus

RELATED CONDITIONS: Cancer of the cervix, Fallopian tube cancer, bladder cancer, vaginal cancer, rectal cancer, ovarian cancer

DEFINITION: The uterus has a body (also called the corpus), which is located within the lower portion of the abdominal cavity between the bladder and the rectum, and a vaginal portion, referred to as the cervix. Although the uterus and cervix are continuous, they are considered as separate structures with respect to cancer. Further, the uterus has a covering (the serosa), a layer of muscle (the myometrium), and a layer of cells (the endometrium) lining the uterine cavity (the uterine cavity is the site for fetal growth during pregnancy). Cancer of the uterus most often involves the endometrium, with the myometrium the less frequent site of cancer. The Fallopian tubes are connected to the top of the uterus on either side but are not considered part of the uterus. Cancer of the uterus is thus defined as cancer of the body of the uterus (the endometrium or myometrium), as opposed to cancer arising from the cervix or metastatic from an adjacent structure (such as the vagina, Fallopian tube, ovary, bladder, or rectum).

Risk factors: Factors that increase the risk of uterine cancer include the use of estrogen-containing medications without the addition of progesterone (called the unopposed estrogen effect; progesterone neutralizes the stimulatory effect of estrogen on the endometrium of the uterus), late menopause, obesity, infertility or not having given birth to a child (also known as nulliparity), diabetes, estrogen-secreting ovarian tumors, polycystic ovarian syndrome, high blood pressure, increased dietary fat intake, Lynch syndrome, radiation therapy to the pelvis for other reasons, and endometrial polyps.

Uterine cancer is more common in Black women than in White women. Black women are also more likely to die from the disease. The five-year relative survival rate for Black women is 64 percent, while for White women with the disease it is 84 percent. Studies have shown that chemical hair straighteners used by many Black women may increase the risk of cancer.

The factors known to decrease a woman’s risk of cancer of the uterus include interrupted ovulation (during and shortly after pregnancy or while using oral contraceptives, which prevent ovulation), use of progesterone as a therapeutic supplement, menopause, normal weight, and having given birth to more than one child (also known as multiparity).

Etiology and the disease process: Cancer of the uterus most often occurs in women in the menopause or those approaching the menopause (that is, perimenopause), with a peak occurrence between the ages of fifty and sixty-five. In women who have long-term unopposed estrogen stimulation, the endometrium undergoes hyperplastic changes that are benign but precede the development of cancer. In most cases, hyperplastic changes can be reversed with the discontinuation of estrogen or the addition of progesterone. The risk of endometrial hyperplasia progressing to cancer increases with age.

Incidence: Cancer of the uterus is the most frequent cancer involving the female reproductive tract in the United States, according to the American Cancer Society in 2024, and the fourth most frequent cancer affecting women, behind breast, lung, and colorectal cancer, according to the American Society of Clinical Oncology (ASCO) in 2023. The American Cancer Society estimated that there would be about 67,880 new cases of cancer of the body of the uterus (both endometrial cancers and uterine sarcomas) in 2024 and that about 13,250 women would die from uterine cancer that year.

Symptoms: Abnormal bleeding through the vagina is the most common symptom associated with cancer of the uterus, occurring in about 90 percent of cases, according to the American Cancer Society in 2019. Such bleeding may arise from the vagina, bladder, or rectum and must be thoroughly evaluated. Fortunately, abnormal bleeding is not always a sign of uterine cancer. For premenopausal women, the bleeding may take the form of breakthrough, prolonged, or heavy bleeding, all of which generally reflect an underlying hormonal imbalance and can be treated as such. For postmenopausal women, any bleeding should be considered abnormal and should be evaluated by a gynecologist. Other symptoms may include pain in the pelvis, a noticeable lump in the pelvic area, and pain during urination or sexual intercourse.

Screening and diagnosis: Unlike cancer of the cervix or breast cancer, which have well-accepted and effective screening tests (Pap smears and mammography, respectively), no simple screening test exists for cancer of the uterus. Nevertheless, two procedures are available for anyone at high risk: endometrial sampling and measurement of the endometrial thickness (or lining).

Endometrial sampling (endometrial biopsy) is an office-based procedure in which a small, flexible, plastic catheter is inserted into the uterus, and the cells lining the uterus (endometrial cells) are aspirated (sucked) into the catheter. Endometrial sampling is a relatively painless procedure, although some women experience mild uterine cramping. The aspirated cells are sent to a laboratory for microscopic evaluation, similar to a Pap smear. Endometrial sampling can also serve as the diagnostic test for endometrial cancer. In some cases, if the diagnosis of uterine cancer is in question based on endometrial sampling, a dilation and curettage (D&C) can be performed as an outpatient procedure in which more extensive sampling of the uterine cavity can be undertaken without causing discomfort to the patient. In rare cases, the diagnosis of uterine cancer is made at the time of a hysterectomy being performed for other indications.

Measurement of the endometrial thickness is also an office-based procedure, but in some cases this is done by a radiologist. An ultrasound probe is inserted through the vagina (transvaginal ultrasound) to measure the thickness of the lining of the uterus. The procedure is painless and takes only a few minutes to perform. Measurement of the endometrial thickness is most appropriate for menopausal women. An endometrial thickness less than 4 millimeters (mm) is rarely associated with a uterine malignancy in a woman not taking hormones, or less than 8 mm in a woman on hormones.

Staging of uterine cancer is according to the International Federation of Gynecology and Obstetrics (FIGO) as follows:

• Stage I: Cancer limited to the endometrium or myometrium
• Stage II: Cancer extending from the body of the uterus to the cervix
• Stage III: Cancer protruding through the serosa or metastases to the vagina, pelvis, or lymph nodes adjacent to the aorta
• Stage IV: Metastases to the bladder, bowel, or organs outside the pelvis in the abdomen

Treatment and therapy: Surgery, typically a hysterectomy with removal of the Fallopian tubes and ovaries and sampling of the local lymph nodes, is the mainstay of treatment. Radiation therapy is reserved for patients who are poor surgical candidates (such as patients with severe heart or respiratory diseases) or have unresectable disease. Chemotherapy is usually of limited value, being used primarily for women with metastatic disease. The blood test for cancer antigen 125 (CA 125) is not diagnostic of cancer of the uterus but can be used to monitor a patient for recurrence.

Prognosis, prevention, and outcomes: Prognostic factors for uterine cancer include age at the time of diagnosis, race (whites have a better prognosis than blacks), tumor stage, tumor grade, type of tumor (adenocarcinoma, clear cell adenocarcinoma, papillary serous adenocarcinoma, sarcoma, and so on), size of the uterus at the time of diagnosis, depth of invasion of the tumor into the layer of uterine muscle, presence of tumor in the blood vessels supplying the uterus, and spread of the tumor outside the uterus to other organs or lymph nodes. According to the ASCO in 2023, the overall five-year survival rates for cancer of the uterus is about 95 percent for local cases, 70 percent when regionally metastasized, and 18 percent with distant spread.

Bibliography

Creasman, W. T., et al. “Carcinoma of the Corpus Uteri: FIGO Annual Report on the Results of Treatment in Gynecological Cancer.” Intl. Journal of Gynaecology and Obstetrics, vol. 95, suppl. 1, 2006, pp. S105–43.

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