Endometrial cancer is a cancer that starts in the lining of the uterus, called the endometrium. It develops from the glandular cells that make up this inner lining, and it is the most common gynecological cancer in developed countries. Most cases are caught early because the disease tends to produce noticeable symptoms, particularly abnormal vaginal bleeding, which prompts women to seek medical attention before the cancer spreads.
Where It Starts and How It Develops
The endometrium is the tissue that thickens each month during the menstrual cycle and sheds during a period. Endometrial cancer arises specifically from the epithelial cells of the endometrial glands. This distinguishes it from uterine sarcoma, a much rarer cancer that develops in the muscular wall of the uterus rather than its lining.
The cancer develops through a process driven largely by hormonal imbalance. Estrogen stimulates endometrial cells to divide, while progesterone counteracts that effect by slowing cell growth. When endometrial cells are exposed to estrogen without enough progesterone to balance it (a situation called “unopposed estrogen”), they divide more rapidly than normal. Over time, this excess cell division can lead to abnormal changes in the lining, progressing from thickening (hyperplasia) to precancerous changes and eventually to cancer.
Type I vs. Type II Cancers
Endometrial cancers fall into two broad categories that behave quite differently. Type I tumors make up the large majority of cases. They are typically endometrioid adenocarcinomas, meaning they resemble normal endometrial gland tissue under a microscope. These cancers are driven by estrogen exposure, tend to be lower grade, and generally have a favorable prognosis. They often develop gradually from a precancerous stage of endometrial hyperplasia, giving doctors a window to catch them early.
Type II tumors are less common, accounting for roughly 10% to 20% of cases, but they are disproportionately deadly, responsible for about 40% of endometrial cancer deaths. These are predominantly serous or clear cell carcinomas. They tend to arise in thinner, atrophic endometrial tissue rather than from estrogen-driven overgrowth, are less well differentiated, and are more likely to have spread at the time of diagnosis. Despite being labeled “estrogen independent,” research has found that many classical risk factors like obesity, early menstruation, and diabetes still apply to Type II cancers as well.
The Most Common Symptom
Abnormal vaginal bleeding is the hallmark warning sign. In a large National Cancer Institute analysis, 90% of women diagnosed with endometrial cancer had reported bleeding before their diagnosis. For postmenopausal women, any vaginal bleeding at all is considered abnormal and should be evaluated. For premenopausal women, warning signs include periods that are unusually heavy, irregular, or bleeding between cycles.
Other symptoms can include watery or blood-tinged vaginal discharge, pelvic pain, and pain during intercourse. However, bleeding is by far the most reliable early signal. The good news is that while postmenopausal bleeding should always be investigated, the overall risk of it actually being cancer is relatively low. The concern is serious enough to warrant testing but not so high that most women with bleeding will receive a cancer diagnosis.
Risk Factors
Obesity is one of the strongest and most modifiable risk factors. Data from the Women’s Health Initiative found that obese women (BMI of 30 or higher) had a 76% increased risk of endometrial cancer compared to women at a normal weight. Obesity may contribute to as many as 40% of all cases. The connection is biological: fat tissue produces estrogen, so carrying excess weight means the endometrium is exposed to higher estrogen levels over a longer period, particularly after menopause when the ovaries stop producing progesterone.
Where fat is distributed matters too. Women with higher waist-to-hip ratios had a 33% increased risk independent of their overall BMI, suggesting that abdominal fat is especially relevant. Other conditions that create a hormonal imbalance work through the same pathway. Polycystic ovary syndrome (PCOS), for example, causes irregular or absent ovulation, which means the body produces estrogen without the cyclical progesterone that normally follows ovulation. Similarly, estrogen-only hormone replacement therapy (without progesterone) increases risk.
Additional risk factors include diabetes, early onset of menstruation, late menopause, never having been pregnant, and older age. Having used combined oral contraceptives, which contain both estrogen and progesterone, is actually protective.
The Role of Genetics
About 2% to 5% of endometrial cancers are linked to an inherited genetic condition, with Lynch syndrome accounting for most of those cases. Lynch syndrome is caused by mutations in genes responsible for repairing DNA copying errors. Women with Lynch syndrome have a significantly elevated lifetime risk of both endometrial and colorectal cancer.
Among endometrial cancer patients diagnosed before age 50, about 9% carry one of these gene mutations. Because of this, tumor tissue is now routinely tested for signs of defective DNA repair. This testing not only identifies women who may have Lynch syndrome (and whose family members should be screened) but also guides treatment decisions for advanced cancer, since tumors with these repair defects often respond well to immunotherapy.
How It’s Diagnosed
When a woman reports postmenopausal bleeding, the first step is usually a transvaginal ultrasound to measure the thickness of the endometrial lining. According to the American College of Obstetricians and Gynecologists, an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for cancer, meaning cancer is extremely unlikely at that measurement. If the lining is thicker than 4 mm, or if it can’t be clearly visualized on ultrasound, a tissue sample is needed.
An endometrial biopsy can be performed in a doctor’s office using a thin, flexible catheter inserted through the cervix. It takes only a few minutes, though it can cause cramping. If the biopsy is inconclusive or the bleeding persists, a more thorough evaluation with hysteroscopy (a small camera placed inside the uterus) or a dilation and curettage procedure may follow. One important caveat: rare aggressive subtypes, particularly Type II serous cancers, can sometimes develop even when the lining appears thin (under 3 mm), so persistent or recurrent bleeding always warrants tissue sampling regardless of ultrasound findings.
Treatment
Surgery is the primary treatment for most endometrial cancers. The standard procedure involves removing the uterus (hysterectomy) along with both fallopian tubes and ovaries. Surgeons also assess whether cancer has spread by evaluating lymph nodes, either through a full dissection or increasingly through sentinel lymph node mapping, a less invasive technique that identifies the first nodes where cancer would drain. Most of these surgeries are now performed minimally invasively, through laparoscopy or robotic-assisted approaches, which means shorter hospital stays and faster recovery compared to open surgery.
For early-stage, low-grade cancers, surgery alone may be all that’s needed. When cancer has spread into the deeper layers of the uterus, into the cervix, or to lymph nodes, radiation therapy is commonly added after surgery to reduce the chance of recurrence. This may involve external beam radiation, vaginal cuff brachytherapy (a localized treatment delivered directly to the top of the vagina), or both. Chemotherapy is typically reserved for higher-grade tumors or more advanced stages.
For advanced or recurrent endometrial cancer, treatment options have expanded significantly. Immunotherapy has become an important tool, particularly for tumors that show deficient DNA mismatch repair (the same defect seen in Lynch syndrome). A landmark trial published in the New England Journal of Medicine demonstrated that combining a targeted therapy with an immunotherapy drug improved outcomes for women with advanced endometrial cancer that had progressed after initial chemotherapy, including those whose tumors had intact DNA repair. This combination is now a standard option for recurrent disease.
Survival Rates by Stage
Because most endometrial cancers cause symptoms early, a large proportion are diagnosed while still confined to the uterus. At this localized stage, the five-year relative survival rate is 95.1%. When cancer has spread to nearby tissues or lymph nodes (regional stage), survival drops to 70.0%. For cancer that has spread to distant organs, the five-year survival rate is 19.4%. These numbers, drawn from national SEER data covering 2015 through 2021, reflect all types of endometrial cancer combined. Women with low-grade, Type I cancers caught early generally do better than these averages suggest, while those with aggressive Type II subtypes may face a more challenging outlook even at earlier stages.