Uterine Cancer: Types, Treatment, and What to Expect

Types of Uterine Cancer

Uterine cancer develops in the uterus (womb). The vast majority of uterine cancers begin in the endometrium, the inner lining of the uterus, and are called endometrial cancers. A smaller number arise from the muscle or connective tissue of the uterus (uterine sarcomas).

Endometrioid Adenocarcinoma

The most common type, accounting for approximately 75-80% of all endometrial cancers. Endometrioid tumors are typically estrogen-driven, meaning they grow in response to estrogen exposure. They are often detected early because they cause abnormal bleeding, and they generally have a favorable prognosis, especially at low grades (grade 1 or 2).

Serous Carcinoma

An aggressive subtype that accounts for about 10% of endometrial cancers but causes a disproportionate share of endometrial cancer deaths. Serous tumors are not estrogen-driven and tend to spread beyond the uterus earlier than endometrioid cancers. They are always considered high-grade and typically require more aggressive treatment, including combination chemotherapy.

Clear Cell Carcinoma

A rare, aggressive subtype that accounts for fewer than 5% of endometrial cancers. Like serous carcinoma, clear cell tumors are high-grade and carry a higher risk of recurrence. Treatment typically follows protocols similar to serous carcinoma.

Carcinosarcoma (Malignant Mixed Mullerian Tumor)

A rare, aggressive tumor containing both carcinoma and sarcoma components. It is now generally classified as a high-grade endometrial carcinoma. Treatment involves surgery followed by chemotherapy, often with carboplatin and paclitaxel.

Uterine Sarcomas

These rare tumors (about 3-7% of uterine cancers) arise from the muscular wall (myometrium) or connective tissue rather than the endometrial lining. Types include leiomyosarcoma (the most common uterine sarcoma), endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Sarcomas are treated differently from endometrial carcinomas.

Risk Factors

Several factors increase the risk of developing endometrial cancer, most of which relate to estrogen exposure:

Estrogen-Related Factors

• Obesity: The single largest modifiable risk factor. Fat tissue produces estrogen, and women with a BMI over 30 have two to four times the risk of endometrial cancer. The risk increases with higher BMI.
• Estrogen-only hormone replacement therapy: Taking estrogen without progesterone (in women with a uterus) significantly increases endometrial cancer risk
• Early menarche or late menopause: More lifetime menstrual cycles mean more cumulative estrogen exposure
• Never having been pregnant (nulliparity): Pregnancy provides a protective effect due to higher progesterone levels
• Polycystic ovary syndrome (PCOS): Causes irregular ovulation and prolonged estrogen exposure without adequate progesterone
• Tamoxifen use: While tamoxifen blocks estrogen in breast tissue, it acts as a weak estrogen in the uterus, slightly increasing endometrial cancer risk

Other Risk Factors

• Lynch syndrome (hereditary nonpolyposis colorectal cancer/HNPCC): Carries a 40-60% lifetime risk of endometrial cancer. Women with Lynch syndrome should discuss early and frequent screening with their doctor.
• Age: Most endometrial cancers are diagnosed in women over 50, with the average age at diagnosis being 60
• Type 2 diabetes: Associated with increased risk, partly due to its association with obesity
• Prior pelvic radiation: Slightly increases risk of uterine cancer years later

Symptoms and Diagnosis

The most common and earliest symptom of endometrial cancer is abnormal vaginal bleeding. In postmenopausal women, any vaginal bleeding should be evaluated promptly. In premenopausal women, unusually heavy periods, bleeding between periods, or a change in menstrual pattern warrants investigation.

Other symptoms may include pelvic pain, a palpable pelvic mass, or unexplained weight loss, though these are more common in advanced disease.

Diagnosis typically involves transvaginal ultrasound to measure endometrial thickness, followed by endometrial biopsy (an office procedure) or dilation and curettage (D&C) to obtain tissue for pathology examination. There is currently no routine screening test for endometrial cancer in average-risk women.

Staging

Uterine cancer is surgically staged, meaning the final stage is determined after the tumor and lymph nodes have been removed and examined by a pathologist.

Treatment Options

Surgery: Hysterectomy

The cornerstone of uterine cancer treatment is total hysterectomy with bilateral salpingo-oophorectomy (removal of the uterus, both fallopian tubes, and both ovaries). This is often performed minimally invasively (laparoscopic or robotic-assisted), which results in shorter hospital stays and faster recovery compared to open surgery.

Sentinel lymph node mapping is increasingly used to assess whether cancer has spread to lymph nodes, avoiding the need for full lymph node dissection in many patients. Pelvic and para-aortic lymph node assessment remains important for staging, particularly in higher-risk tumors.

Radiation Therapy

Radiation therapy is commonly used after surgery to reduce the risk of recurrence. Two forms are used:

• Vaginal cuff brachytherapy: Internal radiation delivered to the top of the vagina. Often used alone for early-stage, intermediate-risk patients. Typically involves three to five sessions.
• External beam radiation therapy (EBRT): Radiation directed at the pelvis from outside the body. Used for higher-risk patients or when cancer has spread beyond the uterus. Usually given five days per week for four to six weeks.

Chemotherapy

Chemotherapy is recommended for advanced-stage disease (stage III-IV) and for aggressive subtypes (serous, clear cell, carcinosarcoma). The most common regimen is carboplatin plus paclitaxel, given every three weeks for six cycles. This combination has become the standard of care based on large clinical trials demonstrating improved survival.

For stage III endometrioid cancers, chemotherapy is often combined with radiation therapy. The GOG-258 and PORTEC-3 clinical trials have helped define the optimal combination strategies.

Hormone Therapy

Hormone therapy with progestins (medroxyprogesterone acetate or megestrol acetate) can be effective for low-grade, estrogen-receptor-positive endometrioid cancers. It is used in several settings:

• Fertility-sparing treatment: For young women with early-stage, low-grade endometrioid cancer who wish to preserve fertility. Treatment involves high-dose progestin with close monitoring by endometrial sampling every three to six months.
• Recurrent disease: Progestins can be used for recurrent low-grade endometrial cancer, especially in patients who are not candidates for further surgery or radiation.
• Combination hormonal therapy: Sometimes combined with other agents like lenvatinib for recurrent disease.

Immunotherapy

Immunotherapy has become an important treatment for a subset of uterine cancers. Key developments include:

• Pembrolizumab (Keytruda) for MSI-H/dMMR tumors: Approximately 25-30% of endometrial cancers have microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status, often related to Lynch syndrome. Pembrolizumab is approved for these tumors and has shown significant response rates.
• Dostarlimab (Jemperli): Another immune checkpoint inhibitor approved for dMMR recurrent endometrial cancer.
• Pembrolizumab plus lenvatinib: This combination is approved for advanced endometrial cancer that is not MSI-H/dMMR and has progressed after prior therapy. The combination of immunotherapy and a targeted therapy (lenvatinib) has shown meaningful responses even in tumors that would not typically respond to immunotherapy alone.

Prevention and Risk Reduction

• Maintain a healthy weight: Weight loss can significantly reduce endometrial cancer risk
• Physical activity: Regular exercise lowers risk, independent of weight
• Combined oral contraceptives: Use of birth control pills reduces endometrial cancer risk by up to 50%, with protection lasting years after discontinuation
• Progestin-containing IUD: The levonorgestrel IUD (Mirena) provides local progestin that protects the endometrium
• Lynch syndrome screening: If you have a family history of Lynch-associated cancers, consider genetic counseling and testing

Last reviewed: March 2026. This information is for educational purposes only and is not a substitute for professional medical advice. Always consult your gynecologic oncologist about your specific diagnosis and treatment plan.