An overview of Endometrial Cancer

1. ENDOMETRIAL
CANCER
Dhammike Silva

2. Commonest female
genital tract
malignancy, 50%
of new cases

3. Epidemiology…
 Mostly in the 6-7th decades of life, 75 - 85%
 Lifetime risk of developing endometrial carcinoma is 2.5%
 Incidence is rising due to
 increased life expectancy,
 obesity epidemic
 fewer hysterectomies performed for benign diseases

4. Pathology…
Type 1 Type 2
80% 20%
endometrioid adenocarcinoma serous, clear cell, squamous and
undifferentiated carcinomas, carcinosarcoma
on a background of atypical hyperplasia
up to 50% of cases of severe atypical
hyperplasia
not associated with the risk factors
hyper-oestrogenic environment
PTEN tumour suppressor gene; k-ras
oncogene, E & P receptors
p53 tumour suppressor gene,
Trans-peritoneal dissemination
good prognosis poor prognosis

5. Spread…
 In rare cases may be metastatic from other tumours
 Breast, ovary, lung, stomach, colorectal, and melanoma
 Direct extension - cervix, vagina, myometrium
 Haematogenous spread- Vaginal metastases (drop-lesions)
 Lymphatic spread- Illiac, obturator, para-aortic nodes
 Involvement of para-aortic nodes is less common if the pelvic
nodes are not involved
 Trans-tubal spread- to the ovaries and peritoneal cavity

6. Risk factors…
accounts for about 40%
The first malignancy to be recognized as being linked to obesity
Obese women have 2-4 times greater risk of developing E. Ca than do
women of a healthy weight,regardless of their menopausal status
Avoiding weight gain lowers the risk of endometrial and
postmenopausal breast CA.
Limited evidence, intentional weight loss will lower risk

7. Tamoxifen…
 Significantly increased (2-5 fold) incidence of endometrial pathology
 Both endometrioid and non-endometrioid endometrial CA can develop
 No evidence to support routine endometrial screening for asymptomatic women
 Bleeding on tamoxifen, hysteroscopic guided biopsy
 Future… aromatase inhibitors as a substitute in the adjuvant treatment of breast
CA

8. Hereditary..
 Less than 5% of all endometrial CA
 BRCA carriers who did not receive tamoxifen do not have a significant increase in
risk
 HNPCC/Lynch II syndrome
 50% of affected women, endometrial CA as index cancer (rather than bowel
cancer)
 No uniform screening strategy
 Risk-reducing hysterectomy, BSO are recommended for those who have
completed their family

9. Diagnosis…
 Mostly presents as PMB - 90%
 Only 10% of women with PMB will have CA
 Persistent postmenopausal vaginal discharge, pyometra
 Pre-menopausal- worsening in menstrual pattern, abnormal endometrial cells on
routine cervical cytology (25- 50%)
 Pelvic examination - to exclude obvious lower genital tracts CA
 Thin endometrium (<5 mm) in the postmenopausal woman has a high negative
predictive value (99%)

10. Pipelle sampling…
 Detection rates for endometrial cancer in postmenopausal and premenopausal
women of 99.6% and 91%, respectively.
 The sensitivity for the detection of endometrial hyperplasia is 81%, with a
specificity of 98%.

11. Imaging…
 To identify metastatic disease and aid treatment decisions
 Chest X-ray to all
 CT of the thorax-
 where the risk of lung metastases is higher e.g. carcinosarcoma
 suspected upper abdominal metastatic disease
MRI - assess the depth of myometrial invasion and to identify extension into cervical
stroma ( sensitive in 92% )

13. Management
 Peritoneal fluid washings for cytologic evaluation
 Total extra-fascial hysterectomy with BSO
 Surgical staging in women considered at risk for extrauterine disease
 Adjuvant therapy to prevent vaginal vault recurrence and to address disease in
lymph nodes

14. Controversies in lymphadenectomy…
 Majority of women with endometrial carcinoma are low-risk for nodal disease at
presentation
 Adjuvant treatment decisions can be based on final pathologic information
 Confirms node-negative/ low-risk status
 avoid pelvic radiation
 recurrence risk is low
 overall survival is high with no radiation or with the substitution of VBT

15. Rationales for routine lymphadenectomy
 Inaccuracy of pre-operative or intraoperative assessments
 Reducing adjuvant therapy use in node-negative women
 Lack of significant morbidity associated with the procedure

16. ‘A Study in the Treatment of Endometrial
Cancer’ (ASTEC)
 Women with stage I endometrial cancer were assigned to have a standard
TAH+BSO with or without lymphadenectomy
 Systematic use of pelvic lymphadenectomy did not improve disease-free or overall
survival in women with early-stage endometrial cancer
 Major complication rate of pelvic lymphadenectomy is approximately
2-6%,
 Argued that the increased use of radiation in unstaged women may produce
similar outcomes to women who are staged and who avoid radiation therapy

20. Drawbacks of ASTEC…
 Utilized a second randomization for pelvic radiation for disease characteristics
 Vaginal vault radiation was permitted as per institutional practice irrespective of the
assignment to pelvic radiation or not
 It makes interpretation of results difficult
 The number of lymph nodes resected was insufficient in many women,

21. An alternative approach for
lymphadenectomy …
 Reserve nodal dissection for women with high risk of nodal disease
 Depth of myometrial invasion is the most important factor
 GOG 33 study- the risk of pelvic nodal disease is around 3% for all women with
grade 1 tumours, increasing to 11% with deeply invasive (outer one-third
myometrial invasion) tumours
 Serous or clear cell histology also warrant nodal dissection, as 30%-50%will have
nodal disease
 Lymphadenectomy improves the carcinoma related survival and the recurrence
free survival in high-risk

22. Extent of lymphadenectomy…
 In full staging, bilateral pelvic and para-aortic lymphadenectomy is increasingly
advocated
 Isolated para-aortic lymph nodes can occur in all grades
 But majority after pelvic LN +
 Para-aortic lymphadenectomy is advocated on all high-risk women, or in women
with two or more positive pelvic lymph nodes
 But a major surgery, in women who are elderly, obese, with co-morbidities

23. Radiotherapy…
 Pelvic radiotherapy (external beam radiotherapy (EBRT) or brachytherapy )
 adjuvant treatment after surgery
 as definitive treatment for women who are medically inoperable
 local recurrence
 Decreases the risk of pelvic recurrence
 No overall survival advantage in women with low-risk endometrial cancer

24. Radiotherapy…

25. Chemotherapy…
 Adjuvant systemic chemotherapy in women with high-risk early-stage endometrial
cancer is still controversial
 PORTEC-3 study
 Two additional GOG studies

26. Predicting nodal disease…
 Positron emission tomography (PET)
 Accurate method for the pre-surgical evaluation of pelvic nodes metastases
 High sensitivity, specificity and positive predictive value.
 Sentinel node identification, data are scant

27. Advanced and recurrent disease…
 Generally preferable to excise the uterus prior to radiotherapy or chemotherapy
particularly where there is troublesome vaginal bleeding and pelvic pain
 Adjuvant external beam radiotherapy to the pelvis and vaginal vault brachytherapy
 Adjuvant chemotherapy to prevent distant disease
 Widespread nodal involvement at presentation is usually palliative
 High-dose oral progestagens

28. Recurrent disease…
 Managed according to the pattern of recurrence and overall fitness
 MRI- evaluation of suspected pelvic recurrence
 CT- abdomen and thorax for other metastases
 Isolated vaginal vault recurrence - either surgery or radiotherapy
 Radiotherapy can also be used with good effect to treat isolated bony metastases

29. Prognosis and follow-up…
 5-year survival rate for all stages is approximately 80%
 Factors that adversely affect prognosis include non-endometrioid histological sub-
type and lymphovascular space invasion
 Recurrence may be suggested by vaginal bleeding, new onset of persistent
backache, significant weight loss or persistent pressure symptoms
 Routine follow-up visit in detecting asymptomatic recurrence and improving
survival from recurrence is unproven

30. Thank you…