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Endometrial Cancer
Endometrial cancer is the most common female genital tract malignancy, with a lifetime risk of developing it being 2.5%. It mostly occurs in women in their 6th-7th decades. Obesity is a major risk factor, accounting for 40% of cases. Diagnosis is usually through post-menopausal bleeding. Treatment involves a total hysterectomy with bilateral salpingo-oophorectomy and surgical staging for high-risk cases. The role of lymphadenectomy is controversial, with some advocating for it only in high-risk cases. Adjuvant radiotherapy decreases pelvic recurrence rates. Prognosis is generally good, with an 80% 5-year survival rate.
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Endometrial Cancer
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- 2. Commonest female genital tract malignancy,50% of new cases
- 3. Epidemiology… Mostly inthe 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 Type2 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 rarecases 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 forabout 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 than5% 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 presentsas 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… Detectionrates 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 identifymetastatic 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 fluidwashings 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 routinelymphadenectomy 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 inthe 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 approachfor 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
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- 25. Chemotherapy… Adjuvant systemicchemotherapy 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 recurrentdisease… 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… Managedaccording 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
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