cancer de endometrio que no es endometroide manejo

ca endometrio

1. ENDOMETRIAL CANCER Nomonde Mbatani

2. Ca Endometrium Most common female genital tract cancer – Developed areas South African females, 7 th most common cancer (1:163) according to SA National Cancer Registry

3. The good news Prognosis excellent

4. Ca endometrium Type 1 Type 2 Obese , hyperlipidaemic . Peri - menopausal woman Mature woman Hyper -estrogenism Atrophic endometrium Precursor - Atypical hyperplasia (EIN) Serous Intra-epithelial Carcinoma-SIC/ EGD ) Low grade. Less invasive at time of surgery High Grade (UPSC, Clear cell, MMMT ? Grade 3 ) Favourable prognosis Poor prognosis Highly sensitive to progestagens No response to progestagens In 80% cases EC In 15 -20% EC

5. Prognostic factors Uterine factors Histological type: Endometrioid , Clear cell, UPSC Histological grade: 1, 2 or 3 (Grigsby, Portec ) LVSI Cervix involvement DNA ploidy – Flow Cytometry Depth of myometrial invasion Extra –uterine factors : More to do with stage! ROLE OF PATHOLOGIST CRUCIAL!

6. Endometrial Cancer Profile The woman with endometrial cancer: Morphological , medical challenge . Pre –operative workup . Anaesthetic assessment ICU bookings

7. Pre-operative Assessment Bloods : FBC, U&E, HIV, δGT , ALP Ultra sound : Liver, lymphadenopathy Depth of myometrial invasion – Role of MRI Histological review!

8. Surgery TAH 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 staging Cuff of vagina – No evidence

9. Parametrial involvement Not part of FIGO staging Some data – associated with poorer prognosis Radical Hysterectomy - ? Survival benefit Small study/ retrospective series Survival in those who were offered radical hysterectomy. Selection bias! Parametrial involvement :Associated with increased surgical stage Still do simple Hysterectomy

10. Type 2 Cancers Additional pelvic / para -aortic lymph node dissection (FIGO Staging) Omentectomy : Serous and MMT. Peritoneal spread - ?Benefit

11. Lymphadenectomy Role Hysterectomy and bilateral salpingo -oophorectomy is the standard surgery followed by RT depending on risk factors Establish extra uterine disease – Stage 3 c(1) or 3c(11) What is the extent? Only pelvic nodes done up to common iliacs – Criticism! FIGO Groin nodes? – No!

12. Is there a survival benefit in LND?

13. A study in Treatment of Endometrial Cancer (ASTEC Study) NO!

14. S urvival E ffect of P ara A ortic L ymphadenectomy ( SEPAL study ) Yes! Intermediate / high risk groups Improved patient survival (OS) in combined LND group (and chemotherapy, independently).p=0049 The higher you go, ……

15. SEPAL

16. S E P A L Study design

17. GSH Protocol TAH 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 involvement Grade 3 or type 2 cancers Cervical involvement If nodes negative: Vault Brachy only vs WPRT, fewer complications for the patient. About 75% patients saved from WPRT

18. 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!

19. Challenges Stage 111 and 1V disease Stage 1V: Adequate cyto reduction – microscopic disease – determinant of survival Other determinants : Age less than 58yrs, good performance status (Bristow) Recurrent disease – Role of surgery

20. Chemotherapy for EC Advanced / recurrent endometrial cancer setting Hormonal therapy – hormone receptor positive tumours (low grade) - (11 to 25% response rates) Medroxy - Progesterone, lower doses as effective - Down regulation of receptors Aromatase inhibitors / SERMS- little data Combinations: Doxorubicin and Cisplatinum Addition of Paclitaxel Toxic regimes : already elderly/ medically unwell patients

21. Targeted therapies

22. Cell growth regulation Proto- oncogenes – Encourage cell growth and inhibit cell death. Mutation – Oncogenes leading to accelerated and disorderly cell growth. Dominant genes Tumour suppressor genes / anti- oncogenes – prevent cell growth and encourage apoptosis: regulate transcription, DNA repair and cell to cell communication.

23. TKR TKR TKR +P P AKT Intracellular events Proliferation Metastasis New vessel formation Decreased apoptosis KRAS RAF PI3K PIP2 PIP3 Cell Membrane Key Hormone ligand Growth factor ligand Prostaglandin  PTEN   ✚ ✚ TKR extracellular domain TKR intracellular domain  +P -P FOXO1 mTor MAPK Type One endometrial cancers

24. Molecular targets Grouping of cancers looking at prognosis What causes diseases What might be manipulated to alter risk / cure disease Design therapeutics

25. Targeted treatments (the future) Molecular profiling Targets cancer pathways Prevention of cancer

26. TKR TKR TKR P P AKT mTor Intracellular : Proliferation Metastasis New vessel formation Decreased apoptosis BRAF MAPK PI3K PIP2 PIP3 Cell Membrane Key Hormone ligand Growth factor ligand Prostaglandin  Bevacizumab – VEGF Lenvatinib Vemurafenib Evorelimus