endometrial cancer endometrial carcinoma gynaecological oncology uterine cancer uterus post menopausal bleeding endometrial neoplasms gynaecology cancer

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