Endometrial carcinoma is the fourth most common cancer among women in the UK, with rising incidence particularly in post-menopausal women. It is classified into two types—Type 1, which is hormone receptor positive with a better prognosis, and Type 2, which is poorly differentiated and associated with worse outcomes. Management involves surgical options like hysterectomy along with adjuvant therapies based on the stage of cancer, with prognosis varying significantly by stage and histological type.

1. Endometrial Carcinoma
Ibrahim Abbass

2. Cancers of the female reproductive tract
• Vulval cancers
• Vaginal cancers
• Cervical cancers
• Endometrial cancers
• Fibroids
• Ovarian cancers
• Other (conceptus, secondary ovarian cancers)

3. Part 1- Endometrial adenocarcinoma
• Epidemiology
• Aetiology & risk factors
• Histology
• Pathophysiology
• Clinical presentation
• Workup
• Management
• Prognosis

4. Epidemiology
• UK incidence: 28/100,000
• 9,000 new UK cases in 2013
• The fourth most common cancer in women in the UK , after breast (31%), lung (12%), bowel
(11%), and more common now than cervical cancer*
• Incidence on the rise in post menopausal European women
• Marked geographical variation: North American: Chinese ratio ≈7:1

5. Aetiology & risk factors
Unopposed oestrogen exposure hypothesis
• Age
• Nulliparity
• Early menarche & late menopause
• HRT
• Obesity & the metabolic syndrome; PCOS
But not
• Combined oral contraceptive

6. Histology
• Classically, endometrial carcinomas have been split into two types based on histological
findings:
• Type 1 “endometrioid” carcinomas are well differentiated (grade 1), hormone receptor positive
neoplasms, typically with a good prognosis. Is generally thought to be preceded by endometrial
hyperplasia, but there is additional dysregulation of the PI3KCA/ AKT signalling pathway, and the
histological pattern of hyperplasia is atypical. Affects women aged 55-65 yrs. Accounts for
around 80% of endometrial adenocarcinomas.
• Type 2 carcinomas are poorly differentiated (grade 3), aneuploid, hormone receptor negative
neoplasms, typically with a poor prognosis. TP53 loss of function. Arises in the setting of
endometrial atrophy, and can be subdivided into serous and clear cell types. Affects women
aged 65-75 yrs. 20% of endometrial carcinomas.

7. Histology (cont.)
Type I Type II- serous

8. Pathophysiology
Type I
Type II

9. Clinical presentation
More common in post menopausal women (75%)
• PMB- always a red flag symptom; 1 in 5 PMB’s are due to malignancy
Pre- or perimenopausal women (25%)
• IMB & menorrhagia

10. Clinical presentation- History
PMHx
• Breast cancer, diabetes mellitus, Lynch syndrome
Menstrual & gynaecological hx
• Early menarche/ late menopause
• Known endometrial hyperplasia
• Parity
DHx
• HRT, tamoxifen, contraception

11. Clinical presentation- Examination
Physical examination may be entirely normal
• Speculum exam of vaginal walls & cervix
• Bimanual palpation

12. Workup
Transvaginal ultrasound- measurement of endometrial thickness; greater than 4-5mm?
Biopsy- endometrial sampling as outpatient
• Pipelle or Vabra cannula (99% and 97% sensitivity; PPV 81%)
• Sample all parts of the uterus
Hysteroscopy & biopsy- only if minimally invasive sampling fails
Dilatation & curettage- no longer performed

13. Workup (cont.)
• Bloods (FBC, LFT’s, U&E’s)
• CXR
• CT/ MRI
Staging (FIGO system)
I- in the body of the uterus only (80%)
II- in the body and the cervix only
III- spread beyond the uterus, but not the pelvis
IV- beyond the pelvis
NICE diagnostic algorithm

14. Management
Surgical
• Partial hysterectomy/ TAH & bilateral salpingo-oophorectomy (BSO)
• Lymphadenectomy
Adjuvant medical therapy
• Radiotherapy (preoperative: brachytherapy- caesium/ radium rods PV; postoperative: external
beam radiation)
• Chemotherapy (Carboplatin; Doxorubicin; Taxol)
• Hormonal therapy (palliative/ fertility preserving therapy): high dose progestogens e.g.
medroxyprogesterone acetate 200mg PO

15. Management (cont.)
FIGO stage I
• Hysterectomy & bilateral salpingo-oophorectomy
FIGO stage II
• Hysterectomy & bilateral salpingo-oophorectomy
• Lymphadenectomy
• ± Radiotherapy ± chemotherapy

16. Management (cont.)
FIGO stage III
• Maximal surgical debulking (including radical hysterectomy, bilateral salpingo-oophorectomy;
possible anterior/ posterior exenteration)
• ± Radiotherapy ± chemotherapy
FIGO stage IV
• Maximal surgical debulking
• Palliative resection of metastases
• ± Radiotherapy ± chemotherapy ± hormone therapy

17. Management (cont.)
• ESMO classify tumours into low, intermediate, high intermediate & high risk groups (based on
stage & grade)
• Low risk: no adjuvant therapy recommended
• Intermediate risk: Adjuvant brachytherapy; however no therapy is an option, especially in
younger patients
• High-intermediate risk & node negative: Adjuvant brachytherapy
• High-intermediate risk & nodal status unknown/ positive: Adjuvant EBRT
• High risk & node negative: Adjuvant EBRT
• High risk & nodal status unknown/ positive: Adjuvant EBRT & chemotherapy

18. Management (cont.)

19. Prognosis
• Prognosis is generally favourable
• Stage is the most important prognosticator
• Grade- serous & clear cell types have poorer outcomes

20. Prognosis (cont.)
One-Year Net Survival (%) by Stage, Women Aged 15-99, England 2014

21. Prognosis (cont.)
Five-Year Relative Survival (%) by Stage, Adults Aged 15-99, Former Anglia Cancer Network 2002-2006

22. Part 1 - Summary
• Often preceded by endometrial hyperplasia; proliferation encouraged by unopposed action of
oestrogen
• Clinically presents as post menopausal bleeding; must always be investigated
• Diagnosed by transvaginal US & endometrial sampling in outpatients; bloods, CXR, CT, MRI for
staging
• Staged using the FIGO system
• Surgical therapies: hysterectomy & lymphadenectomy
• Medical therapies: radiotherapy, chemotherapy, hormone therapies
• Choice of therapy depends on the stage & grade of tumour & risk stratification