Endometrial Cancer: A Plain-Language Overview

Endometrial cancer begins in the endometrium, the lining of the uterus. The American Cancer Society projects about 68,270 new cases of uterine cancer and 14,450 deaths in the United States for 2026, a figure SEER Stat Facts carries; NCI's PDQ summary still quotes the 2025 version. It is the most common gynecologic cancer here and makes up about 7% of all cancers in women.

Most of the risk traces to estrogen that is not balanced by progesterone. PDQ lists obesity and cycles without ovulation. It also lists estrogen-only hormone therapy after menopause. Tamoxifen, taken for breast cancer, is on the list too. Other risks: diabetes, metabolic syndrome, never having given birth, an early first period, and polycystic ovary syndrome. Lynch syndrome raises risk as well.

PDQ calls irregular vaginal bleeding the most common presenting sign, and notes it usually appears early. That is the reason 85% of cases are found at an early stage.

Get evaluated promptly, not eventually, for any of these:

• any vaginal bleeding at all after menopause, even a single spot.
• bleeding or spotting between periods, or periods that become much heavier.
• any new bleeding while taking tamoxifen.
• bleeding that returns after a biopsy came back normal.

That last one matters more than people expect. PDQ notes that endometrial sampling can miss disease, and cites a trial in which 36% of biopsies produced too little tissue to make a diagnosis. A normal result on a scanty sample is not the same as a normal endometrium.

Transvaginal ultrasound, or TVU, measures how thick the lining is. Among women with postmenopausal bleeding who turned out to have cancer, 96% had an endometrial thickness above 6 mm. In one study of women with postmenopausal bleeding, a 4 mm cutoff found 100% sensitivity but only 60% specificity, and 46% of those women measured above 4 mm. In women with no symptoms, the false-positive rate climbs higher still.

That is why PDQ does not support screening healthy women. The same numbers that work in a woman who is bleeding produce a flood of false alarms in a woman who is not.

The diagnosis itself comes from tissue. Endometrial sampling in the office has largely replaced dilation and curettage as the first test. If sampling fails or the bleeding persists, hysteroscopy allows the uterus to be seen directly.

PDQ gives the distribution. Endometrioid carcinoma accounts for about 75%. Uterine papillary serous carcinoma is under 10% and carries a worse outlook. Clear cell carcinoma is about 4%, also with poorer outcomes. Carcinosarcoma is about 3%. It is now grouped as a gland cancer with sarcoma-like change, not as a sarcoma.

The old split is still useful shorthand. Type 1 tumors are estrogen driven and arise from atypical hyperplasia. Type 2 tumors arise from thin, inactive endometrium and behave more aggressively.

The Cancer Genome Atlas sorted these tumors into four molecular groups. PDQ says this testing is encouraged in every patient, where it is available.

• POLE ultramutated: favorable outlook. PDQ notes adjuvant therapy is typically avoided in this group.
• MSI hypermutated, also called mismatch repair deficient or dMMR: intermediate outlook.
• Copy number low, also called no specific molecular profile or NSMP: intermediate outlook.
• Copy number high, also called p53 abnormal: poor outlook.

This is not academic. A grade 3 tumor that turns out to be POLE ultramutated may be spared extra treatment. A tumor that is dMMR opens the door to immunotherapy.

Stage I is confined to the body of the uterus and the ovary. IA means disease limited to the endometrium, or a nonaggressive type invading less than half the muscle wall. IB means a nonaggressive type invading half or more. IC covers aggressive cell types still limited to the endometrium or a polyp.

Stage II reaches the deep tissue of the cervix. It also covers heavy lymphovascular space involvement, meaning tumor inside small vessels. IIA is cervical stromal invasion. IIB is substantial vessel involvement. IIC is an aggressive type with muscle wall involvement.

Stage III means spread near the uterus. IIIA reaches the outer surface, or the ovaries and tubes. IIIB reaches the vagina, or the tissue beside the uterus. IIIC reaches lymph nodes in the pelvis or beside the aorta.

Stage IV means invasion of bladder or bowel lining, or spread to distant sites.

Standard surgery removes the uterus and cervix along with the ovaries and tubes. PDQ prefers keyhole surgery over open surgery. The hospital stay is shorter. Cancer outcomes hold up.

Whether to remove lymph nodes depends on measured risk. PDQ describes three groups. Grade 1 tumors held to the lining carry under 5% node risk. Node removal is not needed. Grade 2 or 3 tumors that invade less than half the wall carry 5% to 9% pelvic node risk. Risk beside the aorta is about 4%. A selective approach is fine. Deep, high-grade, or spread tumors carry 20% to 60% pelvic node risk. Risk beside the aorta runs 10% to 30%. Full node removal is advised.

Sentinel lymph node biopsy maps the first node the tumor drains to and removes only that one. PDQ calls it an adequate substitute for full node removal.

For stage I or II, grade 1 to 2 disease, PDQ describes surgery alone. Vaginal brachytherapy, or internal radiation, is one option instead. Watching without more treatment is fine in very low-risk cases.

Grade 3 and aggressive cell types get more. Treatment adds node removal and chemotherapy after surgery, with or without radiation. Carboplatin and paclitaxel is the preferred regimen for serous and clear cell disease.

Two immunotherapy drugs changed first-line treatment here.

FDA approved pembrolizumab with carboplatin and paclitaxel here. It is for advanced or recurrent disease. The trial was KEYNOTE-868/NRG-GY018, with 810 patients. Chemotherapy was paclitaxel and carboplatin, for 6 cycles every 3 weeks, with both amounts calculated by the treating team. Pembrolizumab was given every 3 weeks during chemotherapy, then on a longer every-6-week schedule for up to 14 more cycles, capped at 24 months. In the dMMR group, median time without the cancer growing was not reached. It was 6.5 months with placebo. The hazard ratio was 0.30. In the mismatch repair proficient group, it was 11.1 months against 8.5 months. The hazard ratio was 0.60.

FDA also approved dostarlimab-gxly with carboplatin and paclitaxel, based on the RUBY trial in 494 patients. Dostarlimab was given every 3 weeks for 6 cycles with chemotherapy, then every 6 weeks for up to 3 years. Median overall survival was 44.6 months against 28.2 months, a hazard ratio of 0.69. That approval no longer requires a dMMR or MSI-high result.

NCI lists three more approved drugs. They are durvalumab, lenvatinib, and megestrol acetate.

PDQ reports a lifetime endometrial cancer risk reaching 60% in Lynch syndrome. Two screening plans are cited. World guidelines call for a yearly scan plus biopsy from age 25 to 35. ACS guidance calls for a yearly biopsy starting at age 35.

If your tumor is dMMR, ask whether that reflects an inherited change or one acquired by the tumor alone. The answer affects your relatives, not only you.

• https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq
• https://www.cancer.gov/types/uterine/hp/endometrial-screening-pdq
• https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma
• https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
• https://www.cancer.gov/about-cancer/treatment/drugs/endometrial
• https://seer.cancer.gov/statfacts/html/corp.html