Endometrial Cancer Flashcards
What is the pathophysiology of endometrial cancer?
Stimulation of the endometrium by oestrogen without the protective effect of progesterone
What are risk factors for endometrial cancer?
- Obesity
- Diabetes mellitus
- Atypical endometrial hyperplasia
Menstrual factors:
- Early menarche
- Late menopause
- Nulliparity
Unopposed oestrogen:
- PCOS
- oestrogen only HRT
- Oestrogen secreting ovarian tumours
- Tamoxifen (E2 agonist at endometrium)
- Lynch syndrome/HNPCC
What is the most common type of endometrial cancer?
Endometrioid carcinoma
What histopathological findings are found in endometrial hyperplasia WITHOUT atypia?
Enlarged glands
Pleiomorphic
Mitosis
What histopathological findings are found in endometrial hyperplasia WITH atypia?
Abnormal glands:
- Dilated
- Budding/infolding of crowded glands
- Increased gland to stroma ratio
Atypia:
- Large, variable shape and size of nuclei
- Loss of polarity
- Increased nuclear to cytoplasmic ratio
- Hyperchromatism,
- Prominent nucleoli
- Abnormal mitotic figures
What were the findings of the Cochrane Review into Laparoscopy vs Laparotomy for Early Endometrial Cancer?
No difference in risk of
- death
- cancer recurrence
Laparoscopy associated with less blood loss and earlier discharge from hospital
In endometrial hyperplasia without atypia, what is the progression to endometrial cancer over 20 years?
<5%
Spontaneous resolution in up to 80%
With progesterone, resolution rates up to 96%
In endometrial hyperplasia with atypia, what is the risk of concomitant carcinoma?
22-43%
In patients undergoing hysterectomy
In endometrial hyperplasia with atypia, what is the risk of progression to endometrial cancer over 20 years?
30%
Spontaneous resolution in up to 30%
What is the standard management for endometrial hyperplasia with atypia?
Hysterectomy +/- BSO depending on menopausal status
What is the fertility sparing option for endometrial hyperplasia with atypia?
LNG IUS
Regression rates up to 86%
Timing of resampling: 6 months, then 12 months
? Role of removal of Mirena 1 month prior to enable accurate pathological assessment, remove pseudodecidualisation effect, progesterone effect
On completion of family, consideration of hysterectomy as risk of malignancy long-term is 11% with cessation of treatment
What % cases of endometrial cancer present premenopausally?
15%
What are two protective factors against endometrial cancer?
COCP
Smoking!
What are the three main lymphatic trunks of the corpus uteri?
Utero-ovarian (infundibulopelvic)
Parametrial
Presacral
They collectively drain into the hypogastric (also known as internal iliac), external iliac, common iliac, presacral and para-aortic nodes.
What are the most common metastatic sites for endometrial / uterine cancer?
Vagina
Ovaries
Lungs
What are the seven histopathological types of endometrial carcinomas?
- Endometrioid carcinoma
- Mucinous adenocarcinoma
- Serous adenocarcinoma
- Clear cell adenocarcinoma
- Undifferentiated carcinoma
- Neuroendocrine tumours
- Mixed carcinoma
What are the five histopathological types of mixed epithelial and mesenchymal uterine tumours?
- Adenomyoma
- Atypical polyploid adenomyoma
- Adenofibroma
- Adenosarcoma
- Carcinosarcoma
What are the two traditional classifications of endometrial cancers?
Type 1 tumours (80%):
- Grade 1 and 2 endometrioid carcinomas
- Risk factor: unopposed oestrogen exposure
- Arise from enodmetrial hyperplasia
- Affects younger, peri-menopausal women
Type 2 tumours (10-20%):
- Grade 3 endometrioid tumours
- Non-endometrioid tumours: serous, clear cell, mucinous, squamous, transitional cell, mesonephric and undifferentiated
- Arise from atrophic endometrium
- Less hormone sensitive
- Less differentiated, poorer prognosis.
- Affects older, post-menopausal women
Who is screening recommended for, in the context of endometrial cancer?
High risk groups ONLY, such as those with Lynch Syndrome
Pipelle and TV USS annually from the age of 35 until hysterectomy
Prophylactic TH+BSO should be discussed at the age of 40
(FIGO, 2018)
What was the key finding of the ASTEC study?
Removing pelvic nodes add staging information but no survival benefit was seen
What is the definition of endometrial hyperplasia?
Irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium
(RCOG GTG)
Why have people advocated that progestogens be used to treat endometrial hyperplasia?
The progestogens modify the proliferative effects oestrogen on the endometrium
Discuss the management of endometrial hyperplasia WITHOUT atypia:
Identify and correct reversible risk factors:
- Weight loss
- Stop oestrogen only HRT or switch to combined HRT.
Observe alone OR commence progestogen treatment (indicated if failure to regress with observation alone or symptomatic with AUB):
- Mirena (1st line): at least 6 months duration; ideally up to 5 years.
- Continuous oral progestogen: at least 6 months duration,
Follow-up:
- Endometrial biopsy every 6 months.
- Need 2 x consecutive negative biopsies before discharging.
- Advise to seek review if abnormal bleeding occurs after completion of treatment.
- High risk women e.g. BMI >=35 or treatment with oral progestogens should have biopsy every 6 months; once 2 x consecutive negative biopsies obtained, increased biopsy interval to every year.
Indications for hysterectomy:
- Progression to atypia
- No regression after 12 months of treatment
- Relapse of hyperplasia after completion of treatment
- Persistence of bleedding
- Declines surveillance / non-compliance with medical treatment.
Choice of surgical approach:
- Laparoscopy preferred: shorter stay, less pain, quicker recovery
- If postmenopausal: offer total hysterectomy with BSO
- If premenopausal: offer total hysterectomy with BS
(RCOG, GTG)
What is the management for a patient with endometrial hyperplasia with atypia?
Surgery (first-line):
- Postmenopausal: total hysterectomy + BSO
- Premenopausal: total hysterectomy + BS; individualise choice of oophorectomy
Fertility sparing treatment OR not suitable for surgery:
- Exclude invasive endometrial cancer, co-existing ovarian cancer
- Refer to gynaecology oncology MDM for advice: management and surveillance.
- Medical treatment: Mirena (1st line) or oral progestogens (2nd line)
- Follow-up usually biopsy every 3/12 until 2 x consecutive negative biopsies then increase interval to every 6 to 12 months until hysterectomy performed.
- When fertility is no longer desired, offer hysterectomy.
How does Tamoxifen increase the risk of endometrial cancer?
- Selective oestrogen receptor modulator
- Indicated in treatment of breast cancer: Inhibits proliferation of breast cancer by competitive antagonism of oestrogen receptors
- Partial AGONIST action on other tissues, including the vagina and the uterus
Estrogenic effect may promote the development of fibroids, endometrial polyps and hyperplasia and in turn, increase the risk of endometrial cancer
What is a woman’s life-time risk of developing endometrial cancer?
2-3%
What is the peak age of incidence of endometrial cancer?
75% of endometrial cancer occur in women over 60 years old.
What is the lymphatic drainage of the uterus?
- Utero-ovarian (infundibulopelvic
- Parametrial
- Presacral
These collective drain into the following lymph nodes:
- Hypogastric (internal iliac)
- External iliac
- Common iliac
- Presacral
- Para-aortic
Define stage I endometrial cancer.
Define stage IA and IB.
Stage I: tumour confined to uterus
Stage IA: No or less than half myometrial invasion
Stage IB: invasion equal to or more than half of myometrium
Define stage II endometrial cancer:
Tumour invasdes cervical stroma but does not extend beyond the uterus.
Define stage III endometrial cancer.
Define stage IIIA, IIIB and IIIC:
Local and/or regional spread of tumour.
Stage IIIA: tumour invades serosa of uterus and/or adnexae
Stage IIIB: vaginal involvement and/or parametrial involvement
Stage IIIC: metastases to pelvic and/or para-aortic lymph nodes
Define stage IV endometrial cancer.
Define stage IVA and IVB:
Stage IV: tumour invades bladder and/or bowel mucosa and/or distant metastases.
Stage IVA: invasion of bladder and/or bowel mucosa.
Stage IVB: distant metastasis including intra-abdominal metastases and/or inguinal nodes.
List the 4 main histopathologic criteria for high risk disease:
- Grade 3 tumour (poorly differentiated)
- LVSI
- Non-endometrioid histology
- Cervical stromal invasion
A postmenopausal woman has a TVUSS showing an endometrial thickness <4 mm; what is her probability of having endometrial cancer?
<1%
How would you screen a woman with Lynch syndrome for endometrial cancer?
TVUSS + pipelle surveillance starting age 35 annually until hysterectomy.
What is the sensitivity and specificity of endometrial pipelle in detecting endometrial cancer?
- Sensitivity 73%
- Specificity 99%
What is the combined negative predictive value of TVUSS and curettage in excluding endometrial cancer?
Negative predictive value 96%
List the investigations you would order in the work up of a woman you suspect has endometrial cancer:
Pipelle biopsy
Imaging:
- TVUSS: ET, uterine cavity fluid
- CXR: lung metastases
- MRI pelvis: depth of invasion, cervical involvement and lymphadenopathy
- CT chest, abdo pelvis or PET-CT: for high risk patients to evaluate lymph nodes and distant metastases
Endoscopy:
- Hysteroscopy D&C: to assess uterine cavity and obtain biopsy
- Cystoscopy: suspected bladder extension
- Proctoscopy: suspected rectal extension
Bloods:
- FBC
- LFTS
- Renal function
When should a woman with endometrial hyperplasia but wishing to conceive start trying?
At least one biopsy should show regression before trying.
Advise her regression is associated with higher implantation and pregnancy rates.
Is letrozole (aromatase inhibitor) associated with endometrial hyperplasia and cancer?
No
What characteristics make an endometrial cancer low risk?
How should these cancers be managed?
- Well differentiated
- <50% myometrial invasion
- <5% positive notes
Full surgical staging not required and total hysterectomy + BSO can be performed by a general gynaecologist.
Describe the steps involved in full surgical staging for endometrial cancer management:
- Midline laparotomy
- Peritoneal washings for cytology
Careful examination +/- biopsy of possible metastases:
- Omentum
- Liver
- Pouch of Douglas
- Adnexae
Extra-fascial total hysterectomy and BSO:
- May consider ovarian preservation in premenopausal women.
If cervical stroma involvement pre-op:
- Simple hysterectomy with free margins + pelvic and para-aortic lymphadenectomy
- OR modified radical hysterectomy and BSO
What is the indications for performing sentinel lymph node mapping?
What are the benefits of SLNM?
Indications:
- Clinical stage I / uterine-confined disease
- If considering lymphadenectomy, you can do SLNM first.
Benefits:
- Reduces morbidity associated with comprehensive lymphadenectomy
- Gives prognostic information from lymph node status
- Sensitivity >90%
Describe the key surgical principles of sentinel lymph node mapping:
- Superficial and deep cervical injection of dye
- Complete evaluation of peritoneal cavity
- Dissection to evaluate retroperitoneal spaces and identify sentinel drainage pathways from the parametria.
- Excision of most proximal lymph nodes in sentinel pathway.
- Remove any suspicious looking lymph nodes
- Use frozen section analysis if available.
- May perform hemipelvic side-specific lymphadenectomy for mapping failure to reduce false-negative staging.
Describe the role of adjuvant radiotherapy in the treatment of endometrial cancer:
Indicated in women with intermediate and high risk factors (at least 2 of):
- Age >60 years
- Deep myometrial invasion
- Grade 3
- Serous or clear cell histology
- LVSI
Combination adjuvant chemoradiation therapy indicated for stage III disease to maximise recurrence-free survival.
How should a woman desiring fertility with grade 1 endometrioid endometrial carcinoma be managed?
Fertility preservation only if no myometrial invasion demonstrated on MRI pelvis.
High dose progestogens:
- Megestrol acetate 160-320 mg/day
- MPA 400-600 mg/day
Refer to fertility clinic and encourage trying to conceive once response obtained.
Hysterectomy once childbearing completed.
What are the management options for stage II disease?
- Radical hysterectomy, BSO, bilateral pelvic lymphadenectomy and selective aortic node dissection.
- Neoadjuvant radiation therapy followed by simple hysterectomy
- Adjuvant radiotherapy: for involved nodes, adverse prognostic factors and close or involved surgical margins
- If surgery not feasible (tumour extension or medically comorbid: full pelvic radiotherapy and intracavitary brachytherapy.
What are the management options of stage III disease?
- Full surgical staging with radical hysterectomy, resection of all pelvic nodes, followed by EBRT and/or chemotherapy.
- If surgical resection not possible: neoadjuvant pelvic radiotherapy +/- chemotherapy, followed by exploratory laparotomy.
What is the follow-up intervals and duration for low risk disease (stage IA, grade 1 and 2)?
- 6 monthly reviews up to 2 years (alternate between GP and surgeon).
- Discharge at 2 years if no symptoms or concerns.
What is the follow-up intervals and duration for intermediate risk disease (stage IA G3, stage IB grades 1 and 2)?
- 6 monthly reviews with surgeon +/- rad onc up to 3 years.
- Discharge at 3 years if not symptoms or concerns.
What is the follow-up intervals and duration for high risk disease (stage IB G3, stages II and III, serous, clear cell and carcinosarcoma)?
- First review at 6 weeks and then 3 monthly reviews with surgeon +/- rad onc for first year.
- 6 monthly reviews for second year
- Discharge at 3 years if not ongoing symptoms or concerns.
