Key Facts

Endometrial cancer is the most common gynaecological malignancy in the UK. Incidence is rising, partly due to increasing obesity rates. The majority present with postmenopausal bleeding, enabling early diagnosis and good prognosis in most cases.

Epidemiology

• UK incidence: approximately 9,700 new cases per year (4th most common female cancer)
• Mortality: approximately 2,400 deaths per year
• Peak incidence: 60-64 years; 75% diagnosed at Stage I
• Incidence increasing by approximately 1% per year (linked to obesity epidemic)
• Rare before age 40 (<5% of cases)

Aetiology

• Type 1 (80%): oestrogen-dependent; risk factors include obesity (BMI >30, RR 2.5-5×), PCOS, nulliparity, early menarche, late menopause, tamoxifen use (2-7× risk), oestrogen-only HRT, diabetes
• Type 2 (20%): non-oestrogen-dependent; risk factors include advanced age, previous pelvic radiotherapy
• Lynch syndrome (HNPCC): 40-60% lifetime risk of endometrial cancer; mismatch repair gene mutations (MLH1, MSH2, MSH6, PMS2)

Pathophysiology

• Type 1: chronic unopposed oestrogen stimulation → endometrial hyperplasia → atypical hyperplasia → carcinoma
• Molecular pathway: PTEN loss, microsatellite instability, PIK3CA mutations
• Type 2: arises de novo from atrophic endometrium; TP53 mutations, HER2 amplification
• Spread: direct myometrial invasion → cervical involvement → lymphatic → peritoneal → haematogenous

Typical Presentation

• Postmenopausal bleeding (PMB): most common symptom (90%); any PMB requires investigation
• In premenopausal women: intermenstrual bleeding, menorrhagia, irregular periods

Advanced Disease

• Pelvic pain
• Abnormal vaginal discharge (blood-stained or purulent, particularly pyometra in elderly)
• Haematuria or rectal bleeding (local invasion)
• Abdominal distension (metastatic disease)

Red Flags

• Any postmenopausal bleeding (endometrial cancer until proven otherwise)
• Persistent intermenstrual bleeding in women >45 years
• Endometrial thickness ≥4mm on TVS in a woman with PMB
• Pyometra in elderly women (may mask underlying malignancy)
• Abnormal glandular cells on cervical screening

Bedside

• Speculum examination: exclude cervical cause of bleeding
• Bimanual examination: uterine size, adnexal masses

Bloods

• FBC (anaemia from chronic blood loss)
• U&Es, LFTs (baseline)
• CA-125 (may be elevated in advanced disease; not diagnostic)

Imaging

• TVS: first-line; endometrial thickness ≥4mm in PMB requires endometrial sampling
• MRI pelvis: for local staging (myometrial invasion depth, cervical involvement, lymph node assessment)
• CT chest/abdomen/pelvis: for distant staging (advanced disease)

Special Tests

• Endometrial biopsy: Pipelle biopsy (outpatient, 90-95% detection rate for cancer); if inadequate → hysteroscopy + biopsy
• Hysteroscopy + curettage: gold standard for diagnosis; allows direct visualisation and targeted biopsy
• Immunohistochemistry and molecular profiling: ER/PR status, MSI/MMR testing, p53, POLE mutation (TCGA molecular classification)
• Lynch syndrome testing: MMR immunohistochemistry on all endometrial cancers (or at least those <60 years)

Non-pharmacological

• MDT discussion (gynaecological oncology, clinical oncology, radiology, pathology)
• Weight loss counselling (reduces recurrence risk)
• Genetic counselling if Lynch syndrome suspected

Pharmacological

• Adjuvant radiotherapy: vaginal vault brachytherapy (VBT) for intermediate-risk Stage I; external beam RT for high-risk features
• Adjuvant chemotherapy: carboplatin + paclitaxel for high-risk histology (Type 2, Stage III-IV)
• Hormonal therapy: high-dose progestogens (medroxyprogesterone acetate 200-600mg OD or Mirena IUS) for:
  • Complex atypical hyperplasia in women wishing to preserve fertility
  • Advanced/recurrent disease (palliative)
• Pembrolizumab + lenvatinib: for advanced MMR-proficient endometrial cancer (KEYNOTE-775 trial)
• Dostarlimab: for dMMR/MSI-high endometrial cancer

Surgical/Interventional

• Standard surgery: total hysterectomy + bilateral salpingo-oophorectomy (TH+BSO); laparoscopic preferred
• Lymphadenectomy: pelvic ± para-aortic; sentinel lymph node mapping increasingly used
• Omental biopsy: for Type 2 histology
• Fertility-sparing: Mirena IUS + high-dose progestogen for complex atypical hyperplasia/early Grade 1 endometrioid in young women (specialist centres only)

Referral Criteria

• PMB in women ≥55: urgent 2-week wait referral (NICE NG12)
• Endometrial thickness ≥4mm on TVS with PMB: urgent referral
• Confirmed endometrial cancer: management in specialist gynaecological oncology centre
• Suspected Lynch syndrome: genetics referral

• Overall 5-year survival: 75-80% (most are diagnosed early)
• Stage IA (no myometrial invasion or <50%): 95%
• Stage IB (≥50% myometrial invasion): 85%
• Stage II (cervical stroma invasion): 75%
• Stage III (local/regional spread): 50-60%
• Stage IV (distant metastases): 15-20%
• Type 2 (serous/clear cell): significantly worse prognosis than Type 1
• Recurrence: 15-20% overall; 50% occur within 2 years

FIGO Staging (Endometrial Cancer)

TCGA Molecular Classification