Endometrial cancer - Symptoms, Causes, Treatment & Prevention

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Overview

Endometrial cancer (also called uterine corpus cancer) originates in the lining of the uterus, known as the endometrium. It is the most common gynecologic malignancy in high‑income countries.

• Incidence: In the United States, approximately 66,000 new cases are diagnosed each year (≈ 4.5 per 100,000 women) – CDC.
• Mortality: Around 10,000 women die annually in the U.S.; the 5‑year survival rate is > 80 % when caught early but drops to < 20 % for advanced disease (Mayo Clinic).
• Age & gender: Almost all cases occur in women; the median age at diagnosis is 62 years.
• Geography: Higher rates in North America, Europe, and Australia; lower rates in parts of Asia and Africa, likely reflecting differences in obesity, hormone use, and reproductive patterns (WHO).

Because the uterus is located deep in the pelvis, early symptoms are often mistaken for benign conditions, making awareness of warning signs essential.

Symptoms

Symptoms can vary, but most women notice at least one of the following:

• Abnormal uterine bleeding:
  • Bleeding between periods (intermenstrual spotting).
  • Heavier, longer periods than usual.
  • Post‑menopausal bleeding (any vaginal bleeding after menopause is a red flag).
• Pelvic pain or pressure: Discomfort that may be constant or occur during intercourse.
• Unexplained weight loss: Particularly when accompanied by other symptoms.
• Feeling of fullness in the lower abdomen: Often due to an enlarged uterus.
• Changes in urinary or bowel habits: Increased frequency or urgency if the tumor presses on nearby organs.
• Fatigue: General tiredness that does not improve with rest.

Because post‑menopausal bleeding accounts for over 90 % of early detections, any vaginal bleeding after menopause warrants prompt evaluation (CDC).

Causes and Risk Factors

The exact cause is unknown, but most cases are linked to hormonal imbalances—specifically excess estrogen without adequate progesterone protection.

Key risk factors

• Age > 50 years – risk rises sharply after menopause.
• Obesity: Body‑mass‑index (BMI) ≥ 30 triples the risk; adipose tissue converts androgens into estrogen (NIH).
• Hormone‑related factors:
  • Early onset of menstruation (< 12 years) or late menopause (> 55 years).
  • Unopposed estrogen therapy (estrogen without progesterone) for menopausal symptoms.
  • Polycystic ovary syndrome (PCOS) – chronic anovulation leads to prolonged estrogen exposure.
• Reproductive history: Never having been pregnant (nulliparity) or infertility raises risk.
• Diabetes mellitus: Particularly type 2, often co‑existing with obesity.
• Family history & genetics:
  • Lynch syndrome (hereditary non‑polyposis colorectal cancer) – up to 40 % lifetime risk of endometrial cancer.
  • Rare hereditary mutations such as PTEN (Cowden syndrome).
• Race & ethnicity: Higher incidence in White and African‑American women; lower in Asian women.
• Previous radiation therapy: Pelvic irradiation for other cancers.

Diagnosis

When endometrial cancer is suspected, clinicians follow a step‑wise work‑up:

1. Clinical evaluation

• Detailed medical and family history.
• Physical exam, including bimanual pelvic exam.
• Transvaginal ultrasound (TVUS) – assesses endometrial thickness; > 5 mm in post‑menopausal women is considered abnormal.

2. Tissue sampling

• Endometrial biopsy: Office‑based procedure using a Pipelle or similar device; yields microscopic diagnosis in > 90 % of cases.
• Dilation & curettage (D&C): Performed if the biopsy is nondiagnostic or if the uterus is large.

3. Staging investigations

Once cancer is confirmed, staging follows the FIGO (International Federation of Gynecology and Obstetrics) system, requiring imaging:

• Pelvic MRI: Preferred for assessing depth of myometrial invasion and cervical involvement.
• CT scan of chest/abdomen/pelvis: Detects distant metastases (lungs, liver, lymph nodes).
• PET‑CT: Useful in high‑risk or recurrent disease.

4. Laboratory tests

• Complete blood count, renal and liver panels – baseline before surgery or chemotherapy.
• CA‑125 is not a diagnostic marker but may be tracked in advanced disease.

5. Genetic counseling

Women with a personal or family history suggestive of Lynch syndrome should be referred for microsatellite instability (MSI) testing or immunohistochemistry for mismatch‑repair proteins.

Treatment Options

Treatment is individualized based on cancer stage, grade, patient’s age, comorbidities, and fertility desires.

1. Surgery

• Total hysterectomy with removal of both fallopian tubes and ovaries (bilateral salpingo‑oophorectomy) – standard for most cases.
• Sentinel lymph‑node mapping: Minimally invasive way to evaluate nodal spread, reducing lymphedema risk.
• Fertility‑preserving surgery: For highly selected stage IA, grade 1 tumors, high‑dose progestin therapy (oral medroxyprogesterone acetate or levonorgestrel IUS) may be offered.

2. Radiation therapy

• External beam radiation therapy (EBRT): Targets the pelvis; used after surgery for high‑risk features.
• Vaginal brachytherapy: Delivers radiation directly to the vaginal cuff, lowering recurrence rates while sparing surrounding tissues.

3. Systemic therapy

• Adjuvant chemotherapy: Carboplatin + paclitaxel is the most common regimen for stage III–IV or high‑grade disease.
• Hormonal therapy: Progestins (megesterol, medroxyprogesterone) for low‑grade tumors, especially in patients who cannot tolerate chemotherapy.
• Targeted agents & immunotherapy:
  • PD‑1 inhibitor pembrolizumab for MSI‑high or mismatch‑repair deficient tumors (Cleveland Clinic).
  • Trastuzumab for HER2‑positive serous carcinomas.

4. Palliative care

For advanced or recurrent disease, focus shifts to symptom control, quality of life, and psychosocial support.

5. Lifestyle & supportive measures

• Weight management and regular exercise improve outcomes and reduce recurrence risk.
• Nutrition counseling to maintain adequate protein and calories during treatment.
• Smoking cessation (although smoking is not a strong risk factor for endometrial cancer, it impairs healing).

Living with Endometrial Cancer

Diagnosis can be overwhelming; the following strategies help patients navigate daily life:

• Follow‑up schedule: Typically every 3–4 months for the first 2 years, then every 6–12 months up to 5 years, and annually thereafter. Visits include physical exam, pelvic imaging, and symptom review.
• Manage treatment side effects:
  • Post‑surgical pain – use prescribed NSAIDs or acetaminophen; avoid heavy lifting for 6–8 weeks.
  • Radiation‑related vaginal dryness – water‑based lubricants or vaginal estrogen (if not contraindicated).
  • Chemotherapy fatigue – schedule rest periods, moderate exercise, and balanced meals.
• Emotional health: Join support groups (e.g., Cancer Support Community), consider counseling, and practice stress‑reduction techniques such as mindfulness.
• Fertility & sexual health: Discuss options with a reproductive specialist; use moisturizers or pelvic floor therapy for sexual discomfort.
• Monitoring for recurrence: Report any new bleeding, pelvic pain, unexplained weight loss, or urinary changes promptly.

Prevention

While not all cases are preventable, risk can be markedly lowered through lifestyle and medical interventions:

• Maintain a healthy weight: Aim for BMI < 25; weight loss of 5–10 % reduces estrogen production from fat.
• Physical activity: ≥ 150 minutes of moderate‑intensity aerobic exercise per week (CDC recommendation).
• Balanced diet: Plenty of fruits, vegetables, whole grains, and limited red/processed meats.
• Hormone management:
  • If menopausal symptoms require estrogen, use combined estrogen‑progestin therapy rather than estrogen alone.
  • Consider a levonorgestrel intrauterine system for abnormal uterine bleeding with protective progestin effect.
• Diabetes control: Good glycemic control may lower risk.
• Screening for high‑risk women: Those with Lynch syndrome should have annual endometrial sampling beginning at age 30–35, per NCCN guidelines.
• Contraceptive use: Combined oral contraceptives reduce lifetime risk by up to 50 % when used for ≥ 5 years (Mayo Clinic).

Complications

If left untreated or when disease progresses, several serious complications can develop:

• Local invasion: Tumor may infiltrate the myometrium, cervix, bladder, or rectum, causing urinary or bowel obstruction.
• Metastasis: Common sites include lungs, liver, bones, and distant lymph nodes.
• Vaginal or pelvic recurrence: Can lead to chronic bleeding and pain.
• Deep‑vein thrombosis (DVT) / pulmonary embolism: Cancer‑associated hypercoagulability increases clot risk.
• Secondary malignancies: Prior radiation therapy may predispose to sarcomas or other cancers.
• Psychosocial impact: Depression, anxiety, and sexual dysfunction are frequent and need addressed.

When to Seek Emergency Care

References

• American Cancer Society. Uterine (Endometrial) Cancer Statistics. 2024. https://www.cancer.org
• Centers for Disease Control and Prevention. Endometrial Cancer Fact Sheet. 2023. PDF
• Mayo Clinic. Endometrial Cancer – Symptoms and Causes. Updated 2024. MayoClinic.org
• National Institutes of Health. Obesity‑Linked Increased Risk of Endometrial Cancer. 2022. NIH.gov
• World Health Organization. Cancer Fact Sheets. 2023. WHO.int
• Cleveland Clinic. Endometrial Cancer Treatment Options. 2024. ClevelandClinic.org

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