Endometrial Cancer

Aka: Endometrial Cancer, Uterine Cancer, Endometrial Carcinoma

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II. Epidemiology

  1. Onset age over 50 years in 90% of cases (mean age is 63 years)
    1. Premenopausal diagnosis of Endometrial Cancer occurs in 20% of cases
  2. Most common gynecologic tract cancer (and the fourth most common cancer overall in women)
    1. Incidence 1.5 times more common than Ovarian Cancer
    2. Incidence 3 times more common than Cervical Cancer
  3. U.S. Statistics estimated for 2025
    1. Incidence: 69,120 new cases per year
    2. Mortality: 13,860 deaths per year
    3. Increasing Incidence (doubling in the last 20 years, esp. related to Obesity)
    4. ACS Cancer facts and figures
      1. https://www.cancer.org/research/cancer-facts-statistics.html

III. Risk Factors

  1. See Endometrial Cancer Risk Factors (also includes protective factors)
  2. Hereditary Nonpolyposis Colorectal Cancer (HNPCC, Lynch Syndrome) are at high risk of Endometrial Cancer
    1. Offer annual Endometrial Biopsy starting at age 35 years
  3. Paradoxically, Tobacco use is associated with a lower Incidence of Uterine Cancer

IV. Types

  1. Type I - Endometrial Adenocarcinoma or Endometrioid (75-80% of cases)
    1. Typically associated with Unopposed Estrogen with Endometrial Hyperplasia as a precursor
  2. Type II - Non-Endometrioid (10%)
    1. Not associated with Unopposed Estrogen, Endometrial Hyperplasia or other typical Endometrial Cancer Risks
    2. Includes serous, papillary, clear cell, mucinous, squamous, an adenosquamous types
    3. Onset at older age, more advanced stage and with worse prognosis (accounts for 40% of mortality)
    4. Most common in black women over age 50 years old
  3. Familial Tumors (10%)
    1. Most associated with Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC)
    2. HNPCC confers a 22-50% lifetime risk of Endometrial Cancer

V. Pathophysiology

  1. See Endometrial Hyperplasia (precursor of Type I, endometrioid cancers)

VI. Symptoms: Presentation (90% of cases)

  1. Abnormal Uterine Bleeding (most common presenting symptom)
  2. Abnormal Vaginal Discharge
  3. Accompanying symptoms suggestive of advanced disease
    1. Abdominal Pain or Pelvic Pain
    2. Abdominal Distention or bloating
    3. Early satiety
    4. Change in bowel or Bladder habits

VII. Exam

  1. Evaluate for other sources of bleeding (e.g. vagina, Cervix)
  2. Bimanual exam

VIII. Evaluation

  1. See Endometrial Cancer Screening
    1. Covers Indications (includes Endometrial Hyperplasia)
    2. Includes evaluation with Trasvaginal Ultrasound and Endometrial Biopsy
  2. See Dysfunctional Uterine Bleeding

IX. Imaging

  1. Pelvic Ultrasound (transvaginal and transabdominal Ultrasound)
    1. See Endometrial Cancer Screening for Ultrasound recommendations
    2. Endometrial thickness <4 mm in POSTmenopausal women may exclude Endometrial Cancer
      1. Endometrial stripe thickness is unreliable in PREmenopausal women
  2. At time of Endometrial Cancer diagnosis
    1. Chest XRay
    2. Trasvaginal Ultrasound (if not already performed)
    3. Consider Pelvic MRI

X. Labs

  1. Urine Pregnancy Test
  2. Endometrial Biopsy
  3. Pap Smear (if due)
    1. AGUS on Pap Smear may suggest Endometrial Hyperplasia or Endometrial Cancer

XI. Staging

  1. See Endometrial Cancer Staging

XII. Differential Diagnosis

  1. See Anovulatory Bleeding
  2. Endometrial Atrophy
  3. Endometrial Hyperplasia
  4. Endometrial Polyps
  5. Cervical Cancer
  6. Cervical Polyps
  7. Coagulopathy
  8. Uterine Fibroids

XIII. Management

  1. Precautions
    1. Biopsy may under-grade Endometrial Cancer (e.g. Grade I is really a Grade 3)
  2. Surgery
    1. Total Hysterectomy with bilateral salpingoophorectomy
      1. First-line management in Stages I-III
      2. Tumor debulking in Stage IV Endometrial Cancer
      3. Vaginal Hysterectomy is not recommended
        1. Does not allow for abdominal evaluation or lymphadenectomy
    2. Peritoneal washings (pelvic washings)
      1. Indicated in Stages I-III
    3. Para-aortic or pelvic Lymph Node dissection may be needed depending on staging
      1. Indicated in Stages I-III
  3. Radiation Therapy (external beam or vaginal brachytherapy)
    1. Indicated in Stages II, III
    2. Consider in Stage I if high-risk prognosis
    3. Decreases local and regional recurrence rates
    4. Does NOT improve survival in Stage I and II Endometrial Cancers
    5. Ideally used in combination with surgery for best efficacy
      1. However may be considered in non-surgical candidates
  4. Systemic therapy (indicated in Stages III, IV)
    1. Progestins
      1. Indicated in recurrence with distant metastases
      2. Consider in patients unable to tolerate first-line therapy
    2. Tamoxifen 20 mg orally twice daily
      1. Consider in patients not responding to Progesterone therapy
      2. Response in 20% of patients failing Progesterone therapy
    3. Chemotherapy
      1. Doxorubicin (Adriamycin)
      2. Mitotic Inhibitor Chemotherapy (e.g. Paclitaxel, Docetaxel, Carboplatin)
    4. Immunotherapy
      1. Improves response to Chemotherapy
      2. VEGFR Monoclonal Antibody (Bevacizumab)
      3. Immune Checkpoint Inhibitor (Pembrolizumab, Dostarlimab)
  5. Post-treatment surveillance (Cancer Survivor Care)
    1. History and exam every 3-6 months for 2-3 years, then every 6-12 months up to year 5, then yearly
      1. Include speculum exam and pelvic exam
      2. Pap Smear of the vaginal cuff after Hysterectomy is NOT recommended
    2. Cancer Antigen 125 monitoring if initially elevated (per oncology)
    3. Imaging as indicated for findings suggestive of recurrence
      1. Imaging surveillance is not recommended for asymptomatic women
    4. Carek (2024) Am Fam Physician 110(1): 37-44 [PubMed]

XIV. Prognosis

  1. See Endometrial Cancer Staging
  2. Five year survival varies by sub-stage
    1. Localized Endometrial Cancer: 95%
    2. Regional Endometrial Cancer: 70%
    3. Distant Endometrial Cancer: 19%

XV. Prevention

  1. Consider prophylactic Hysterectomy at age 40 years old for women with Lynch Syndrome
  2. Manage Unopposed Estrogen states
    1. Consider Oral Contraceptive or Progesterone IUD
    2. Obesity Management with weight loss

XVI. References

  1. Braun (2016) Am Fam Physician 93(6): 468-74 [PubMed]
  2. Bryce (2025) Am Fam Physician 111(6): 526-31 [PubMed]
  3. Buchanan (2009) Am Fam Physician 80(10): 1075-88 [PubMed]
  4. Sorosky (2008) Obstet Gynecol 111(2 pt 1): 436-47 [PubMed]

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