Endometrial Cancer (Uterine Cancer)

What endometrial cancer is

The endometrium thickens each month under the influence of estrogen and sheds during a period. After menopause it normally stays thin. When the lining is exposed to estrogen without enough progesterone to balance it, cells can overgrow (endometrial hyperplasia) and, in some cases, become cancerous.

Types

Doctors now also classify endometrial cancers by molecular type (POLE-mutated, mismatch repair deficient, p53-abnormal and no specific molecular profile), which helps predict outlook and guide treatment.

Symptoms

• bleeding after menopause: the most important sign. About 90% of people with endometrial cancer have abnormal bleeding. Only a minority of postmenopausal bleeding is cancer, but it must always be checked
• irregular, heavy or prolonged bleeding in perimenopause, or bleeding between periods
• watery, pink or brown discharge after menopause
• pelvic pain or pressure
• pain during sex
• in advanced disease: weight loss, belly swelling, a change in bowel or bladder habits

Risk factors

Most are linked to estrogen exposure without progesterone:

• obesity: fat tissue converts hormones into estrogen. Obesity is linked to a large share of cases
• estrogen-only hormone therapy in people with a uterus
• polycystic ovary syndrome and irregular ovulation
• early first period, late menopause and never having been pregnant
• tamoxifen for breast cancer
• type 2 diabetes and insulin resistance
• age: most diagnoses are after 50
• Lynch syndrome: an inherited condition with a lifetime endometrial cancer risk of up to about 40 to 60%, depending on the gene
• previous pelvic radiation

Factors that lower risk include combined hormonal contraception, progestin IUDs, pregnancy, breastfeeding and physical activity.

Diagnosis

1. Pelvic examination.
2. Transvaginal ultrasound: measures endometrial thickness. In postmenopausal bleeding, a thin lining (4 mm or less) makes cancer unlikely, according to ACOG, though persistent bleeding still needs a biopsy.
3. Endometrial biopsy: a thin tube takes a sample of the lining in the office.
4. Hysteroscopy with D&C: a camera views the inside of the uterus and samples tissue if the biopsy is inconclusive.
5. Staging tests: CT or MRI, and the final stage is confirmed by surgery.

All endometrial cancers are now tested for mismatch repair status, which screens for Lynch syndrome and guides immunotherapy.

Stages

Most cases are diagnosed at stage I because bleeding appears early.

Treatment

Surgery

• Total hysterectomy and removal of both tubes and ovaries, usually by minimally invasive laparoscopic or robotic surgery.
• Sentinel lymph node mapping to check whether the cancer has spread to nodes, with less risk of leg swelling (lymphedema) than removing many nodes.

Additional treatment

• vaginal brachytherapy (internal radiation) or external pelvic radiation for higher-risk early disease
• chemotherapy (usually carboplatin and paclitaxel) for advanced or aggressive types
• immunotherapy (such as dostarlimab or pembrolizumab) combined with chemotherapy, particularly effective in mismatch repair deficient tumors
• hormone therapy (progestins and others) for some advanced or recurrent low-grade cancers
• targeted therapy such as trastuzumab for HER2-positive serous cancers

Fertility-sparing treatment

For selected young people with early, low-grade endometrioid cancer or atypical hyperplasia who wish to preserve fertility, high-dose progestin therapy, often with a progestin IUD, under close monitoring may be an option.

Outlook

Survival depends mainly on stage and type. According to American Cancer Society data, the 5-year relative survival rate is about 95% for cancer confined to the uterus, about 70% for regional spread and around 18 to 20% for distant spread. Aggressive types and older age carry a less favorable outlook. Follow-up visits every 3 to 6 months for the first 2 to 3 years focus on new symptoms such as bleeding.

Prevention and early detection

There is no routine screening test for endometrial cancer in average-risk people. The best protection is to report any postmenopausal bleeding promptly. Other measures:

• maintain a healthy weight and stay active
• if taking estrogen with a uterus, use it combined with a progestin
• people with Lynch syndrome may be offered yearly checks and risk-reducing hysterectomy after childbearing

Frequently asked questions

What is the first sign of endometrial cancer?

The most common first sign is abnormal vaginal bleeding, especially any bleeding or spotting after menopause. Before menopause, bleeding between periods or unusually heavy or prolonged periods can be warning signs. Watery or blood-tinged discharge can also occur.

Is endometrial cancer the same as uterine cancer?

Endometrial cancer is by far the most common type of uterine cancer, so the terms are often used interchangeably. Uterine cancer also includes rarer uterine sarcomas, which arise from the muscle wall and behave differently.

Is postmenopausal bleeding always cancer?

No. Most postmenopausal bleeding is caused by thinning of the vaginal or uterine lining, polyps or hormone therapy. However, around 1 in 10 cases is endometrial cancer, so any bleeding after menopause should be checked promptly with an ultrasound or biopsy.

What is the survival rate for endometrial cancer?

When diagnosed while still confined to the uterus, the 5-year relative survival rate is about 95%. It is around 70% when the cancer has spread to nearby lymph nodes or tissues and much lower for distant spread. Outlook also depends on the tumor type and molecular features.

Can endometrial cancer be prevented?

Not entirely, but risk can be lowered by maintaining a healthy weight, staying active, using progestin with any estrogen therapy if you have a uterus, and using combined hormonal contraception or a progestin IUD where appropriate. People with Lynch syndrome may consider preventive surgery.