Definition
Endometrial cancer is a malignancy originating from the lining of the uterus (endometrium).
- Most common gynecologic cancer in developed countries.
- Classified into two main types:
- Type I (Endometrioid): Estrogen-dependent, usually low-grade, better prognosis.
- Type II (Non-endometrioid: serous, clear cell, carcinosarcoma): Estrogen-independent, high-grade, poor prognosis.
Epidemiology
- Median age at diagnosis: ~60 years.
- Risk factors differ by type.
Risk Factors
Type I (Endometrioid, estrogen-driven)
- Obesity (↑ peripheral estrogen)
- Nulliparity, early menarche, late menopause
- Tamoxifen use
- PCOS, metabolic syndrome
Type II (Serous, clear cell)
Other Genetic Factors
Pathogenesis / Molecular Features
| Type | Molecular Alterations | Clinical Relevance |
|---|---|---|
| Type I (Endometrioid) | PTEN loss, PIK3CA, KRAS, MSI-H | Often MSI-H → responsive to immunotherapy |
| Type II (Serous) | TP53 mutations, HER2 amplification | Aggressive, often requires chemotherapy |
Clinical Features
- Abnormal uterine bleeding (most common, postmenopausal spotting)
- Pelvic pain, bloating, or mass effect in advanced disease
- Often early-stage diagnosis due to bleeding
Diagnostics
- Transvaginal ultrasound (endometrial thickness assessment)
- Endometrial biopsy (histopathology)
- Imaging: MRI, CT for staging
- Molecular testing: MMR, MSI, HER2, POLE mutation
Treatment (Oncology Pharmacy Focus)
Surgery
- Total hysterectomy + bilateral salpingo-oophorectomy
- Pelvic/para-aortic lymph node assessment for staging
- Cytoreduction may be considered in advanced disease
Adjuvant Therapy
- Radiation therapy: Vaginal brachytherapy or external beam (high-risk early-stage)
- Chemotherapy: Carboplatin + Paclitaxel (high-risk or advanced disease)
Targeted / Immunotherapy
- Immunotherapy: Pembrolizumab for MSI-H/dMMR tumors
- HER2-targeted therapy: Trastuzumab for HER2-positive serous endometrial carcinoma
Supportive Care
- Anti-emetics, growth factors if chemotherapy-induced myelosuppression
- VTE prophylaxis in high-risk patients
Prognosis
- Type I: Usually early-stage, good prognosis (5-year survival >80%)
- Type II: Aggressive, often advanced at diagnosis, poorer prognosis