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Endometrial Cancer

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An overview of Endometrial Cancer

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Endometrial Cancer

  1. 1. ENDOMETRIAL CANCER Dhammike Silva
  2. 2. Commonest female genital tract malignancy, 50% of new cases
  3. 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. 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. 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. 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. 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. 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. 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. 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. 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% )
  12. 12. 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
  13. 13. 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
  14. 14. 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
  15. 15. ‘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
  16. 16. 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,
  17. 17. 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
  18. 18. 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
  19. 19. 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
  20. 20. Radiotherapy…
  21. 21. Chemotherapy…  Adjuvant systemic chemotherapy in women with high-risk early-stage endometrial cancer is still controversial  PORTEC-3 study  Two additional GOG studies
  22. 22. 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
  23. 23. 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
  24. 24. 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
  25. 25. 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
  26. 26. Thank you…

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