Endometrial cancer

Overview

Endometrial cancer is the most common gynaecological malignancy in the developed world - the fourth most common cancer in women in the UK. 80-90% are adenocarcinomas. Central mechanism: prolonged unopposed oestrogen stimulation of the endometrium.

Risk factors

Almost all risk factors relate to increased oestrogen exposure or absent progesterone opposition.

Risk factors - increased oestrogen / absent progesterone

Obesity - aromatase in adipose converts androgens to oestrone

Nulliparity - fewer anovulatory cycles shed with progesterone

Late menopause / early menarche - prolonged exposure

Unopposed oestrogen HRT - no progestogen opposition

Tamoxifen - partial oestrogen agonist in uterus

Type 2 diabetes - hyperinsulinaemia → IGF-1 receptor stimulation

PCOS - chronic anovulation

Lynch syndrome (HNPCC) - 30-60% lifetime risk; consider in young women

Presentation

•Postmenopausal bleeding (PMB) - cardinal symptom; ~90% of cases; must exclude malignancy in all cases

•Abnormal uterine bleeding - in pre-menopausal women: intermenstrual bleeding, menorrhagia, or irregular cycles

•Vaginal discharge - blood-stained or watery

•Pelvic pain - suggests locally advanced disease

🚨

Postmenopausal bleeding is endometrial cancer until proven otherwise. ~75% of women present with Stage 1 disease because PMB prompts early presentation. Atrophic vaginitis is a far more common cause of PMB but must be excluded by investigation, not assumed.

Investigations

🥇 First-line

•Transvaginal ultrasound scan (TVUSS) - endometrial thickness >4mm in a postmenopausal woman mandates further investigation

🏆 Gold standard

•Endometrial biopsy (pipelle or hysteroscopy-guided) - histological confirmation of diagnosis, tumour type and grade

🥈 Second-line

•CT chest/abdomen/pelvis - staging, lymphadenopathy, distant metastases

•MRI pelvis - superior for local extent; assesses depth of myometrial invasion and cervical stromal involvement

⚠️

Pipelle biopsy has a false-negative rate of ~10-15%. A negative pipelle in a high-risk patient with persistent symptoms warrants hysteroscopy. Hysteroscopy is preferred when polyps or focal lesions are suspected - allows direct visualisation and targeted biopsy.

Differential diagnosis

Key differentials for postmenopausal bleeding

Diagnosis	Distinguishing features
Atrophic vaginitis	Most common cause of PMB; thin endometrium on TVUSS; characteristic vaginal appearance on speculum
Endometrial hyperplasia	Precursor lesion; cannot distinguish from cancer clinically or on imaging; biopsy required; atypical hyperplasia ~32% concurrent cancer risk
Endometrial polyp	Localised (not generalised) endometrial thickening on TVUSS; hysteroscopy is definitive
Cervical cancer	Visible cervical lesion on speculum; postcoital bleeding; colposcopy and biopsy distinguish

Management

•First-line (curative): Total hysterectomy + bilateral salpingo-oophorectomy (BSO) + pelvic lymphadenectomy - laparoscopic preferred where eligible

•Adjuvant radiotherapy (brachytherapy ± external beam) - for intermediate/high-risk Stage 1-2 to reduce local recurrence; primary radiotherapy for women unfit for surgery

•Adjuvant chemotherapy (carboplatin + paclitaxel) - for advanced Stage 3-4 or high-grade disease, often combined with radiotherapy

•Hormonal therapy (progestogens e.g. medroxyprogesterone acetate) - for low-grade endometrioid cancer with fertility-preservation wishes, or those unfit for surgery; not standard curative treatment

📌

Referral: women aged ≥55 with PMB → 2-week wait (2WW) urgent cancer pathway. Women <55 with PMB → consider 2WW. All confirmed cases discussed at gynaecological oncology MDT before treatment.

Prognosis

5-year survival by FIGO stage

Stage	Description	5-year survival
Stage 1	Confined to uterus	>85-90%
Stage 2	Cervical stromal involvement	~70-80%
Stage 3	Regional spread	~40-60%
Stage 4	Distant metastases	~15-25%