Uterus
- Home
- Cancer Infomation
Uterine Cancer
Uterine cancer, primarily occurring as Endometrial Carcinoma (EC), is the most common gynecological malignancy in developed nations. clinical management has evolved from a purely histological assessment to a molecular-integrated classification system. This shift allows for precise risk-stratification, often sparing low-risk patients from aggressive over-treatment while identifying high-risk candidates for early immunotherapy.
Etiology & Risk Factors
The pathogenesis of endometrial cancer is generally categorized into Type I (estrogen-dependent) and Type II (estrogen-independent),
though molecular subtyping is now the preferred clinical framework.
Environmental & Lifestyle Triggers:
- Unopposed Estrogen: This remains the primary driver. It can result from early menarche, late menopause, nulliparity, or estrogen-only hormone replacement therapy (HRT).
- Obesity: Peripheral conversion of androstenedione to estrone in adipose tissue creates a hyperestrogenic state. obesity-associated chronic inflammation is also recognized as a direct pro-carcinogenic driver.
- Polycystic Ovary Syndrome (PCOS): Chronic anovulation leads to prolonged estrogen exposure without the protective effect of progesterone.
- Tamoxifen Use: While protective for breast cancer, it acts as an estrogen agonist on the endometrium.
Genetic Predispositions:
- Lynch Syndrome (HNPCC): Caused by germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2). Women with Lynch syndrome have a 40ā60% lifetime risk of uterine cancer.
- Cowden Syndrome: Mutations in the PTEN gene.
Molecular Subsets :
- POLE Ultramutated: Excellent prognosis; often allows for treatment de-escalation.
- Mismatch Repair Deficient (dMMR): Highly responsive to immunotherapy.
- p53 Abnormal (p53abn): Aggressive; typically requires intensified systemic therapy.
- No Specific Molecular Profile (NSMP): Intermediate prognosis.
Clinical Manifestations
Uterine cancer often presents early because the primary symptomāabnormal
bleedingāis highly noticeable.
Early-Stage Symptoms:
- Postmenopausal Bleeding (PMB): Any bleeding after menopause is uterine cancer until proven otherwise (found in >90% of cases).
- Abnormal Uterine Bleeding (AUB): In pre- or perimenopausal women, this includes heavy, irregular, or intermenstrual bleeding.
Advanced-Stage Symptoms:
- Pelvic Pain or Pressure: Indicative of a large uterine mass or local extension.
- Abdominal Distention: May signify ascites or omental "caking" (common in serous subtypes).
- Change in Bowel/Bladder Habits: Due to extrinsic compression by the tumor.
Paraneoplastic Syndromes:
- Rare, but can include Trousseau Sign (migratory thrombophlebitis) or Paraneoplastic Cerebellar Degeneration.
Diagnostic Workup
The diagnostic pathway emphasizes “molecular triage”
at the time of initial biopsy.
- 1. Transvaginal Ultrasound (TVUS): The first-line tool to measure endometrial thickness (ET).
- 2. Endometrial Biopsy (Pipelle): The gold standard for initial office-based diagnosis.
- 3. Dilation and Curettage (D&C) with Hysteroscopy: Performed if the Pipelle biopsy is inconclusive or if a focal lesion is suspected.
- 4. Molecular Reflex Testing: every new diagnosis of EC automatically undergoes IHC for MMR proteins and p53, plus POLE sequencing, ER,PR,Her 2 neu IHC to guide the surgical and adjuvant plan.
- 5. Liquid Biopsy: Used post-operatively to monitor ctDNA for molecular recurrence, particularly in high-risk p53abn or serous histologies.
Common Investigations & Staging
Imaging Modalities & Rationale
- Pelvic MRI (with Contrast): The modality of choice for local staging. It evaluates the depth of myometrial invasion and cervical stromal involvement, which are critical for surgical planning.
- CT Abdomen/Pelvis: Used to assess for distant metastases (omentum, liver) and bulky lymphadenopathy.
- FDG PET-CT: Primarily used for staging high-grade histologies (Serous, Clear Cell, Carcinosarcoma) or when recurrent disease is suspected.
- Chest Imaging: Routine CT chest is mandatory for high-grade tumors to rule out pulmonary metastases.
Treatment Overview
1. Surgery
- Standard Care: Total Laparoscopic (or Robotic) Hysterectomy with Bilateral Salpingo-Oophorectomy (TLH/BSO).
- Sentinel Lymph Node (SLN) Mapping: SLN mapping using Indocyanine Green (ICG) has largely replaced systematic lymphadenectomy for apparent early-stage disease, significantly reducing the risk of lymphedema.
- Fertility-Sparing Approach: For young patients with Grade 1 endometrioid EC, progestin therapy (LNG-IUD) may be considered under strict surveillance if no myometrial invasion is present.
2. Radiotherapy
- Vaginal Brachytherapy (VBT): Used as adjuvant therapy for intermediate-risk disease to reduce local recurrence with minimal toxicity.
- External Beam Radiation (EBRT): Utilizes IMRT/VMAT for Stage II or III disease to treat the pelvic nodes and parametria.
3. Systemic Therapy
- Chemotherapy: The combination of Carboplatin and Paclitaxel remains the backbone for advanced or recurrent disease.
- Immunotherapy (Checkpoint Inhibitors):
- Dostarlimab or Pembrolizumab: Now used as first-line therapy in combination with chemotherapy for patients with dMMR/MSI-H tumors.
- Targeted Therapy: Lenvatinib + Pembrolizumab is the standard for p53abn or pMMR (mismatch repair proficient) recurrent disease.
Emerging Therapies
- Antibody-Drug Conjugates (ADCs): New ADCs targeting HER2 (for serous tumors) and FRĪ± (Folate Receptor alpha) are showing high efficacy in platinum-resistant uterine cancers.
- AI-Predictive Histopathology: AI models now analyze digital biopsy slides to predict POLE or MMR status instantly, allowing for surgical planning even before genetic sequencing is complete.
- WEE1 Inhibitors: Specifically targeting the p53abn pathway to induce mitotic catastrophe in aggressive serous subtypes.
Medical Disclaimer
This guide is intended for professional medical use.
Treatment decisions must be individualized and made within a multidisciplinary tumor board (MDT).
Guidelines are subject to update; always consult the latest NCCN or institutional protocols for patient care.