Uterine Cancer

Uterine cancer is the most common gynecologic malignancy in developed countries, primarily affecting the endometrium (lining of the uterus). It typically occurs in postmenopausal women and presents with vaginal bleeding, pelvic pain, and sometimes palpable masses. Early detection through recognition of symptoms and regular gynecological care significantly improves treatment outcomes and survival rates.

Medical Disclaimer: This information is for educational purposes only. Vaginal bleeding after menopause or unusual bleeding patterns require immediate medical evaluation. Contact your healthcare provider promptly for proper diagnosis and treatment.

Overview

Uterine cancer encompasses malignancies arising from the uterus, with endometrial cancer accounting for approximately 95% of cases. This cancer typically develops in the endometrium, the hormone-sensitive lining of the uterus that undergoes cyclical changes during menstruation. The disease predominantly affects women after menopause, with the average age of diagnosis being 60 years old.

The incidence of uterine cancer has been steadily increasing, largely attributed to rising obesity rates, earlier menarche, later menopause, and decreased fertility rates in developed countries. Fortunately, most cases are diagnosed at an early stage due to the characteristic symptom of abnormal vaginal bleeding, which prompts women to seek medical attention. When detected early, uterine cancer has excellent survival rates, with five-year survival exceeding 95% for stage I disease.

There are two main histological types of endometrial cancer: Type I (endometrioid) tumors, which are estrogen-dependent and generally have a better prognosis, and Type II (non-endometrioid) tumors, including serous and clear cell carcinomas, which are more aggressive and estrogen-independent. Understanding these distinctions is crucial for determining appropriate treatment strategies and predicting outcomes.

Symptoms

Uterine cancer symptoms can be subtle initially but typically become more pronounced as the disease progresses. Recognition of these warning signs is crucial for early detection and optimal treatment outcomes.

Primary Symptoms

  • Vaginal bleeding after menopause - the most common and significant symptom, occurring in 90% of cases
  • Abnormal menstrual bleeding in premenopausal women (heavier, longer, or more frequent periods)
  • Spotting or bleeding between menstrual periods
  • Watery or blood-tinged vaginal discharge

Pain and Discomfort

  • Pelvic pain - may be constant or intermittent, often described as cramping or pressure
  • Lower abdominal pain or bloating
  • Pain during intercourse (dyspareunia)
  • Lower back pain that may radiate to the legs

Physical Changes

  • Groin mass - enlarged lymph nodes that may be palpable
  • Abdominal distension or feeling of fullness
  • Unexplained weight loss
  • Fatigue and weakness

Advanced Disease Symptoms

  • Difficulty urinating or changes in urination patterns
  • Bowel changes or difficulty with bowel movements
  • Leg swelling (lymphedema)
  • Shortness of breath (if disease spreads to lungs)
  • Bone pain (if metastasis to bones occurs)

Associated Risk Factors

Certain factors increase the likelihood of developing uterine cancer:

  • Obesity - increases estrogen production in fat tissue
  • Diabetes mellitus - often associated with obesity and metabolic syndrome
  • Hypertension - part of metabolic syndrome
  • Never having been pregnant (nulliparity)
  • Late menopause (after age 52)
  • Early menarche (before age 12)

Causes

Uterine cancer develops through a complex interplay of genetic, hormonal, and environmental factors. Understanding these causes helps in both prevention strategies and treatment decisions.

Hormonal Factors

Estrogen Exposure

  • Prolonged unopposed estrogen exposure is the primary risk factor for Type I endometrial cancer
  • Estrogen stimulates endometrial growth without adequate progesterone to balance the effect
  • Sources include early menarche, late menopause, and estrogen-only hormone replacement therapy
  • Obesity increases estrogen production through aromatization in adipose tissue

Reproductive Factors

  • Nulliparity (never having been pregnant) increases risk due to lack of progesterone protection
  • Infertility, often associated with anovulation and unopposed estrogen
  • Polycystic ovary syndrome (PCOS) causing irregular ovulation

Genetic Factors

  • Lynch syndrome: Hereditary nonpolyposis colorectal cancer syndrome increases risk 40-60%
  • Family history: Having relatives with endometrial, ovarian, or colorectal cancer
  • PTEN mutations: Associated with Cowden syndrome
  • TP53 mutations: More common in aggressive Type II cancers

Medical Conditions

  • Diabetes mellitus: Independent risk factor, possibly through insulin resistance
  • Hypertension: Often associated with metabolic syndrome
  • Endometrial hyperplasia: Precancerous condition, especially with atypia
  • Tamoxifen use: While protective for breast cancer, increases endometrial cancer risk

Lifestyle Factors

  • Obesity: Most significant modifiable risk factor, increases risk 2-3 fold
  • Physical inactivity: Contributes to obesity and metabolic dysfunction
  • Diet: High-fat, low-fiber diets may increase risk
  • Smoking: Paradoxically may decrease risk by reducing estrogen levels

Risk Factors

Multiple factors influence the likelihood of developing uterine cancer. Understanding these helps in risk assessment and prevention strategies.

Non-Modifiable Risk Factors

  • Age: Risk increases with age, peaking in the 60s
  • Race: White women have higher incidence, but Black women have worse outcomes
  • Family history: Genetic predisposition, especially Lynch syndrome
  • Personal history: Previous breast or ovarian cancer

Hormonal Risk Factors

  • Early menarche: Before age 12 increases lifetime estrogen exposure
  • Late menopause: After age 52 prolongs estrogen exposure
  • Nulliparity: Never having been pregnant
  • Infertility: Often associated with anovulation
  • Hormone replacement therapy: Estrogen-only formulations

Metabolic Risk Factors

  • Obesity: BMI >30 kg/m² increases risk significantly
  • Type 2 diabetes: Independent risk factor
  • Metabolic syndrome: Cluster of metabolic abnormalities
  • PCOS: Associated with insulin resistance and anovulation

Medication-Related Factors

  • Tamoxifen: Selective estrogen receptor modulator
  • Unopposed estrogen therapy: Without progesterone protection
  • Some fertility drugs: When used for extended periods

Protective Factors

  • Pregnancy and breastfeeding: Protective due to progesterone exposure
  • Combined oral contraceptives: Long-term use provides significant protection
  • Progestin-containing IUDs: Local progesterone effect
  • Physical activity: Regular exercise reduces risk
  • Healthy weight maintenance: Reduces estrogen production

Diagnosis

Diagnosis of uterine cancer involves a systematic approach combining clinical evaluation, imaging studies, and definitive tissue sampling. Early and accurate diagnosis is crucial for optimal treatment planning and outcomes.

Clinical Evaluation

History and Physical Examination

  • Detailed menstrual and reproductive history
  • Assessment of bleeding patterns and associated symptoms
  • Family history of gynecologic and colorectal cancers
  • Medical history including diabetes, obesity, and medication use
  • Pelvic examination to assess uterine size and mobility
  • Examination for lymphadenopathy and abdominal masses

Imaging Studies

Transvaginal Ultrasound

  • First-line imaging for postmenopausal bleeding
  • Measures endometrial thickness (>4mm in postmenopausal women is abnormal)
  • Assesses myometrial invasion depth
  • Evaluates ovaries and adnexa

MRI (Magnetic Resonance Imaging)

  • Superior for assessing myometrial invasion depth
  • Evaluates cervical involvement
  • Useful for surgical planning
  • May identify enlarged pelvic lymph nodes

CT Scan

  • Chest, abdomen, and pelvis for staging purposes
  • Identifies distant metastases
  • Assesses retroperitoneal lymphadenopathy
  • Evaluates other organ involvement

Tissue Sampling

Endometrial Biopsy

  • Office-based procedure using suction curette
  • High sensitivity for detecting endometrial cancer
  • Provides histologic diagnosis and grading
  • May be inadequate in some cases requiring D&C

Dilatation and Curettage (D&C)

  • More comprehensive sampling under anesthesia
  • Used when office biopsy is inadequate or impossible
  • May be combined with hysteroscopy for direct visualization

Hysteroscopy

  • Direct visualization of endometrial cavity
  • Allows targeted biopsy of suspicious areas
  • Can identify polyps or other focal lesions
  • May be diagnostic or therapeutic

Laboratory Tests

  • Complete blood count to assess for anemia
  • Comprehensive metabolic panel
  • CA-125 (may be elevated in advanced disease)
  • Liver function tests if metastases suspected

Staging

FIGO (International Federation of Gynecology and Obstetrics) staging system:

  • Stage I: Confined to uterine corpus
  • Stage II: Involves cervical stroma
  • Stage III: Local/regional spread
  • Stage IV: Distant metastases

Treatment Options

Treatment of uterine cancer is individualized based on stage, histologic type, grade, patient age, and overall health status. A multidisciplinary approach involving gynecologic oncologists, radiation oncologists, and medical oncologists optimizes outcomes.

Surgical Treatment

Primary Surgery

  • Total hysterectomy with bilateral salpingo-oophorectomy:
    • Standard treatment for most endometrial cancers
    • May be performed open, laparoscopic, or robotic
    • Includes removal of fallopian tubes and ovaries
  • Lymph node assessment:
    • Sentinel lymph node mapping increasingly used
    • Pelvic and para-aortic lymphadenectomy for high-risk cases
    • Guides adjuvant therapy decisions
  • Omentectomy: For papillary serous and clear cell histology

Minimally Invasive Approaches

  • Laparoscopic surgery with faster recovery
  • Robotic-assisted surgery for complex cases
  • Vaginal hysterectomy in selected patients
  • Similar oncologic outcomes to open surgery

Radiation Therapy

External Beam Radiation Therapy (EBRT)

  • Adjuvant therapy for intermediate and high-risk disease
  • Pelvic radiation to reduce local recurrence
  • Extended field radiation for para-aortic involvement
  • Intensity-modulated radiation therapy (IMRT) to spare normal tissues

Brachytherapy

  • Vaginal cuff brachytherapy for low-risk disease
  • Lower toxicity than external beam radiation
  • Effective for preventing vaginal recurrence
  • Can be combined with EBRT for high-risk cases

Systemic Therapy

Chemotherapy

  • Adjuvant chemotherapy:
    • For advanced stage or high-risk histology
    • Carboplatin and paclitaxel standard regimen
    • Improves overall survival in stage III-IV disease
  • Neoadjuvant chemotherapy: For inoperable disease
  • Palliative chemotherapy: For recurrent or metastatic disease

Hormone Therapy

  • Progestins (megestrol acetate, medroxyprogesterone)
  • For low-grade, hormone receptor-positive tumors
  • Young women desiring fertility preservation
  • Recurrent disease with slow progression

Targeted Therapy

  • Immunotherapy: Pembrolizumab for mismatch repair deficient tumors
  • mTOR inhibitors: Everolimus for recurrent disease
  • CDK4/6 inhibitors: Under investigation

Treatment by Stage

  • Stage I: Surgery ± adjuvant therapy based on risk factors
  • Stage II: Surgery + radiation ± chemotherapy
  • Stage III: Surgery + chemotherapy ± radiation
  • Stage IV: Individualized approach, often palliative

Supportive Care

  • Management of treatment-related side effects
  • Nutritional support and counseling
  • Physical therapy and rehabilitation
  • Psychological support and counseling
  • Palliative care for advanced disease

Prevention

While not all cases of uterine cancer can be prevented, several strategies can significantly reduce risk, particularly for women with modifiable risk factors.

Lifestyle Modifications

  • Weight management:
    • Maintain healthy BMI (18.5-24.9 kg/m²)
    • Even modest weight loss reduces risk
    • Balanced diet with adequate fruits and vegetables
    • Limit processed foods and excessive calories
  • Regular physical activity:
    • At least 150 minutes moderate exercise weekly
    • Helps maintain healthy weight
    • Improves insulin sensitivity
    • Reduces estrogen levels

Medical Prevention

  • Oral contraceptive use:
    • Combined pills provide significant protection
    • Effect lasts years after discontinuation
    • Benefit increases with duration of use
  • Progestin therapy:
    • For women with PCOS or irregular cycles
    • Levonorgestrel-releasing IUD
    • Cyclical progestin for anovulatory women
  • Diabetes management:
    • Optimal glucose control
    • Metformin may have protective effects
    • Regular monitoring and treatment

Screening and Early Detection

  • No routine screening: for average-risk asymptomatic women
  • High-risk surveillance:
    • Annual endometrial biopsy for Lynch syndrome carriers
    • Starting at age 35 or 5 years before earliest family diagnosis
    • Consider prophylactic hysterectomy after childbearing
  • Symptom awareness:
    • Prompt evaluation of postmenopausal bleeding
    • Investigation of abnormal bleeding patterns
    • Regular gynecological examinations

Genetic Counseling

  • Family history assessment
  • Genetic testing for Lynch syndrome
  • Risk-reducing surgical options
  • Enhanced surveillance protocols

When to See a Doctor

Seek immediate medical attention for:

Schedule routine consultation for:

  • Family history of endometrial, ovarian, or colorectal cancer
  • Personal history of breast or ovarian cancer
  • Known Lynch syndrome or genetic predisposition
  • Chronic anovulation or PCOS
  • Long-term tamoxifen use
  • Unopposed estrogen therapy

Annual gynecological exams recommended for:

  • All women over age 21
  • Earlier if sexually active
  • Discussion of individual risk factors
  • Preventive strategies and screening needs

High-risk individuals should discuss:

  • Enhanced surveillance protocols
  • Genetic counseling and testing
  • Risk-reducing interventions
  • Family planning considerations

Related Conditions

References

  1. National Comprehensive Cancer Network. Uterine Neoplasms. NCCN Clinical Practice Guidelines in Oncology. Version 1.2024.
  2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233-254.
  3. Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. Lancet. 2016;387(10023):1094-1108.
  4. Brooks RA, Fleming GF, Lastra RR, et al. Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69(4):258-279.
  5. American College of Obstetricians and Gynecologists. Committee Opinion No. 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding. Obstet Gynecol. 2018;131(5):e124-e129.
  6. Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol. 2016;27(1):16-41.