Endometrial cancer is the fourth most common cancer in women. In the United Kingdom,
7,536 cases were diagnosed in 2007 and there were 1,741 deaths in 2008. Between 1971 and 2005 the there was a fall in mortality by 27% in the UK. The 10 year survival rate of endometrial carcinoma is 75% (1).
The majority of endometrial cancer occurs in postmenopausal women,
but up to 25% of cases may be premenopausal (2).
The lifetime risk of developing endometrial carcinoma is 1.7–2%,
and the incidence is rising with an increase in life expectancy and in risk factors (Table 1),
such as obesity (3).
Risk Factors associated with endometrial carcinoma
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Obesity
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Late menopause (>52 years old)
|
Nulliparity
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Diabetes mellitus
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Tamoxifen therapy and oral contraceptive pill
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Prolonged unopposed oestrogen exposure
|
Hypertension
|
Family history of endometrial or breast cancer
|
Personal history of ovarian or breast cancer
|
Table 1: Risk factors associated with endometrial carcinoma(4)
The majority of women with endometrial carcinoma present with inter-menstrual or post-menopausal bleeding,
with 75-80% presenting with stage I disease (5).
There are several different histological subtypes of endometrial carcinoma. The most common is endometrial adenocarcinoma (90%). Less common subtypes include adenocarcinoma with squamous differentiation,
adenosquamous carcinoma,
papillary serous carcinoma and clear cell carcinoma.
The last 2 histological subtypes are considered the most aggressive and,
along with grade III endometrial adenocarcinoma,
are associated with a worse prognosis (4). (See Table 2 for prognostic indicators).
Factors Affecting Prognosis
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Patient age
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Histologic grade of tumour
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Deep myometrial invasion
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Cervical invasion
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Extra-uterine spread
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Lymph node involvement
|
Table 2: Prognostic indicators in endometrial carcinoma(4,5)
A typical clinical presentation occurs with symptoms of abnormal bleeding per vaginum and referral from a primary care physician to a dedicated hospital clinic.
Assessment often consists of history,
examination,
ultrasound examination to assess for endometrial thickness and cytological assessment by pipelle endometrial sampling.
If this sampling is inadequate,
particularly in patients with an abnormally thickened endometrium on ultrasound,
direct tissue biopsy via hysteroscopy is often then employed.
Accurate staging of endometrial cancer is vital.
Both effective treatment and prognosis relates directly to tumour stage at presentation.
As with all gynaecological malignancies the International Federation of Gynecology and Obstetrics (FIGO) staging system is used.
This is very similar to TNM classification staging system widely used for other solid organ malignancies.
Gynaecological staging systems have been present from the 1920s and FIGO itself was derived from pre-war League of Nations staging criteria.
Originally FIGO staging was based on anatomical extent of disease assessed on clinical examination but with time has become both surgically and pathologically based.
Modern pre-operative staging relies on magnetic resonance imaging (MRI) to triage presenting patients into differing treatment arms.
MRI provides the most accurate radiological modality for assessing tumour invasion,
particularly in the vast majority of cases where tumour remains confined to the uterine corpus.
The FIGO staging was revised in 2009 for the first time in a decade (Table 3 & 4).
Stage
|
Surgico-Pathologic Findings
|
IA
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Tumour limited to the endometrium
|
IB
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Invasion to less than half of the myometrium
|
IC
|
Invasion equal to or more than half the myometrium
|
IIA
|
Endocervical glandular involvement only
|
IIB
|
Cervical stromal invasion
|
IIIA
|
Tumour invades the serosa of the corpus uteri and/or adnexae and/or positive peritoneal cytological findings
|
IIIB
|
Vaginal metastases
|
IIIC
|
Metastases to pelvic and/or paraaortic lymph nodes
|
IVA
|
Tumour invasion of bladder and/or bowel mucosa
|
IVB
|
Distant metastases,
including intra-abdominal metastasis and/or inguinal lymph nodes
|
Table 3: The previous 1998 FIGO Staging for Endometrial Cancer
Stage
|
Surgico-Pathologic Findings
|
I
|
Tumour confined to uterine body
|
IA
|
No or less than one-half myometrial invasion
|
IB
|
Invasion equal to or more than one half of the myometrium
|
II
|
Tumour invades cervical stroma,
but does not extend beyond the uterus
|
III
|
Local and / or regional spread of the tumour
|
IIIA
|
Tumour invades the serosa of the corpus uteri and / or adnexae
|
IIIB
|
Vaginal and / or parametrial involvement
|
IIIC
|
Metastases to pelvic and / or para-aortic lymph nodes
|
IIIC1
|
Positive pelvic nodes
|
IIIC2
|
Positive para-aortic lymph nodes with or without positive pelvic lymph nodes
|
IV
|
Tumour invades bladder and /or bowel mucosa,
and / or distant metastases
|
IVA
|
Tumour invasion of bladder and/or bowel mucosa
|
IVB
|
Distant metastases,
including intra-abdominal
Metastases and / or inguinal lymph nodes
|
Table 4: The revised 2009 FIGO Staging for Endometrial Cancer
2009 FIGO Staging Modifications
The 4 main modifications to the 1998 FIGO staging criteria are as follows:
1. Myometrial Invasion
In the 1998 FIGO staging criteria,
stage IA referred to disease within the endometrium,
but with preservation of the junctional zone and no myometrial involvement. Stage IB referred to disease that invaded the myometrium by less than 50%. On review,
it was found that there was minimal survival difference between the two groups,
therefore in the 2009 FIGO staging criteria these groups have been combined.
Stage IA now describes disease involving the endometrium and / or less than 50% of myometrial thickness. Stage IB now describes invasion of the tumour into the outer half of the myometrium (previously classified as IC disease)(5,6).
2. Cervical Involvement
In the 2009 FIGO staging criteria,
stage II is no longer divided into stage IIA and IIB. Involvement of the endocervical glands is now considered stage I and involvement of the cervical stroma is regarded as stage II.
3. Nodal Disease
Para-aortic node involvement is considered to have a poor prognosis; therefore,
the staging of pelvic and para-aortic node involvement has now been separated into: Stage IIIC1 positive pelvic nodes and stage IIIC2 positive para-aortic nodes with or without positive pelvic nodes.
4. Peritoneal Cytology
Peritoneal cytology is no longer included in the FIGO staging criteria,
however it must still be reported(5).
Full FIGO staging necessitates a total hysterectomy,
bilateral salpingo-oophorectomy,
acquisition of peritoneal fluid or washings,
a thorough exploration of the abdominal cavity and pelvic and para-aortic nodal areas and full pelvic lymphadenectomy (7).
Although the rate of lymph node involvement in endometrial carcinoma is low (5-8%),
lymphadenectomy is still part of the FIGO staging. However,
the complication rate of lymphadenectomy is between 17-19%,
which can be even higher in high-risk surgical candidates (8,
9). Therefore,
most centres will reserve pelvic lymphadenectomy for those patients in which there is a high pre-operative risk for nodal invasion (Table 5) based on histology or imaging.
Factors Affecting the Likelihood of Lymph Node Invasion
|
Tumour grade
|
Depth of myometrial invasion
|
Degree of cervical invasion
|
Table 5: Factors affecting the likelihood of lymph node invasion
By defining the depth of myometrial invasion and the presence of cervical involvement,
pre-operative MRI allows for accurate treatment planning i.e.
selection of women who would benefit from lymph node resection and those who would need adjuvant therapy (11).