Ca Endometrium Most common female genital tract cancer Developed areas South African females 7 th most common cancer 1163 according to SA National Cancer Registry The good news Prognosis excellent ID: 1041121
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2. ENDOMETRIAL CANCERNomonde Mbatani
3. Ca EndometriumMost common female genital tract cancer – Developed areasSouth African females, 7th most common cancer (1:163) according to SA National Cancer Registry
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5. The good newsPrognosis excellent
6. Ca endometriumType 1 Type 2Obese , hyperlipidaemic. Peri - menopausal womanMature womanHyper -estrogenismAtrophic endometriumPrecursor - Atypical hyperplasia (EIN)Serous Intra-epithelial Carcinoma-SIC/ EGD)Low grade. Less invasive at time of surgeryHigh Grade (UPSC, Clear cell, MMMT ?Grade 3)Favourable prognosisPoor prognosisHighly sensitive to progestagensNo response to progestagensIn 80% cases ECIn 15 -20% EC
7. Prognostic factors Uterine factorsHistological type: Endometrioid, Clear cell, UPSCHistological grade: 1, 2 or 3 (Grigsby, Portec)LVSICervix involvementDNA ploidy – Flow CytometryDepth of myometrial invasion Extra –uterine factors: More to do with stage! ROLE OF PATHOLOGIST CRUCIAL!
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9. Endometrial Cancer ProfileThe woman with endometrial cancer: Morphological , medical challenge .Pre –operative workup.Anaesthetic assessment ICU bookings
10. Pre-operative AssessmentBloods: FBC, U&E, HIV, δGT, ALPUltra sound: Liver, lymphadenopathyDepth of myometrial invasion – Role of MRIHistological review!
11. SurgeryTAH and BSO – Open / Laparoscopic – Curative for most women (75% - confined to uterus)Laparoscopy: Conversion to open surgery is higher Peritoneal washings – No longer part of stagingCuff of vagina – No evidence
12. Parametrial involvementNot part of FIGO stagingSome data – associated with poorer prognosisRadical Hysterectomy - ? Survival benefit Small study/ retrospective seriesSurvival in those who were offered radical hysterectomy. Selection bias!Parametrial involvement :Associated with increased surgical stageStill do simple Hysterectomy
13. Type 2 CancersAdditional pelvic / para-aortic lymph node dissection (FIGO Staging)Omentectomy: Serous and MMT. Peritoneal spread - ?Benefit
14. LymphadenectomyRoleHysterectomy and bilateral salpingo-oophorectomy is the standard surgery followed by RT depending on risk factorsEstablish extra uterine disease – Stage 3 c(1) or 3c(11)What is the extent?Only pelvic nodes done up to common iliacs – Criticism! FIGOGroin nodes? – No!
15. Is there a survival benefit in LND?
16. A study in Treatment of Endometrial Cancer (ASTEC Study)NO!
17. Survival Effect of Para Aortic Lymphadenectomy (SEPAL study) Yes!Intermediate / high risk groupsImproved patient survival (OS) in combined LND group (and chemotherapy, independently).p=0049The higher you go, ……
18. SEPAL
19. SEPAL Study design
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21. GSH ProtocolTAH and BSO – For low risk patients (Stage 1) Stage 1a and Grade 1/ 2 and less than 50% invasion Low risk of recurrence (5%) No survival benefit Intermediate risk: Grade 1/ 2 with more than 50% mm involvementGrade 3 or type 2 cancersCervical involvementIf nodes negative: Vault Brachy only vs WPRT, fewer complications for the patient.About 75% patients saved from WPRT
22. Intermediate risk: G. Thomas Grade 2 Stage 1b / Grade 3 WPRT vs Vault Brachytherapy – No survival advantage,Does not lead to better cure Pelvic recurrences: curable with radiotherapy risks:benefit. First do no harm! Keep as Plan B. Especially in patients under age 60yrs with no LVSI – GOG and Portec seem to suggest!
23. ChallengesStage 111 and 1V diseaseStage 1V: Adequate cyto reduction – microscopic disease – determinant of survivalOther determinants: Age less than 58yrs, good performance status (Bristow)Recurrent disease – Role of surgery
24. Chemotherapy for ECAdvanced / recurrent endometrial cancer settingHormonal therapy – hormone receptor positive tumours (low grade) - (11 to 25% response rates) Medroxy - Progesterone, lower doses as effective - Down regulation of receptorsAromatase inhibitors / SERMS- little dataCombinations: Doxorubicin and CisplatinumAddition of PaclitaxelToxic regimes: already elderly/ medically unwell patients
25. Targeted therapies
26. Cell growth regulationProto- oncogenes – Encourage cell growth and inhibit cell death. Mutation – Oncogenes leading to accelerated and disorderly cell growth. Dominant genesTumour suppressor genes / anti- oncogenes– prevent cell growth and encourage apoptosis: regulate transcription, DNA repair and cell to cell communication.
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28. TKRTKRTKR+PPAKTIntracellular eventsProliferationMetastasisNew vessel formationDecreased apoptosisKRASRAFPI3KPIP2PIP3Cell MembraneKeyHormone ligandGrowth factor ligandProstaglandin PTEN✚✚TKR extracellular domain TKR intracellular domain+P-PFOXO1mTorMAPKType One endometrial cancers
29. Molecular targetsGrouping of cancers looking at prognosisWhat causes diseasesWhat might be manipulated to alter risk / cure disease Design therapeutics
30. Targeted treatments (the future)Molecular profilingTargets cancer pathwaysPrevention of cancer
31. TKRTKRTKRPPAKTmTorIntracellular:ProliferationMetastasisNew vessel formationDecreased apoptosisBRAFMAPKPI3KPIP2PIP3Cell MembraneKeyHormone ligandGrowth factor ligandProstaglandinBevacizumab – VEGF LenvatinibVemurafenib Evorelimus
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