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Carcinoma dell’Endometrio Cronoprogramma Diagnostico-Terapeutico

Carcinoma dell’Endometrio Cronoprogramma Diagnostico-Terapeutico. CARCINOMA ENDOMETRIALE. Sensibile aumento di incidenza In Italia 5-6-% dei tumori femminili 4-5000/ casi anno e 1700 decessi/anno. Diagnosticato in fase iniziale raggiunge tassi di sopravvivenza fino al 90%.

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Carcinoma dell’Endometrio Cronoprogramma Diagnostico-Terapeutico

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  1. Carcinoma dell’Endometrio Cronoprogramma Diagnostico-Terapeutico

  2. CARCINOMA ENDOMETRIALE Sensibile aumento di incidenza In Italia 5-6-% dei tumori femminili 4-5000/ casi anno e 1700 decessi/anno. Diagnosticato in fase iniziale raggiunge tassi di sopravvivenza fino al 90%

  3. CARCINOMA ENDOMETRIALE Accuratezza stadiazione clinica Chirurgia adeguata (isterectomia, linfoadenect., etc) Terapie adiuvanti ( sovra-sottotrattamento) Incremento sopravvivenza Riduzione morbilità iatrogena Migliore qualità della vita

  4. da riferire urgentemente al Ginecologo • Sanguinamento in post-menopausa (no TOS) • Sanguinamento in post-menopausa (sospensione TOS >=6 sett.) • Sanguinamento in post-menopausa (Tamoxifene)

  5. Perdite Ematiche Atipiche Eco Pelvi TV HRT/TAM Endometrio >8/10 mm Endometrio <4/5 mm Endometrio >4/5 mm Isteroscopia + biopsia endometriale Rassicurante Normale Pat. Ben Cancro Rassicurante Terapia Riferimento

  6. ! ENDOMETRIAL CARCINOMA The management of patients with early stage EC is probably the least uniform when compared to that for patients with other gynecological malignancies

  7. EC - Scottish Pop-based StudyStaging Quality & Survival (Crawford, 2002) 79% of pts operated on by surgeons with <=5 EC pt caseload

  8. Stadiazione FIGO (2009) I Tumor confined to the corpus uteri IA No or less than half myometrial invasion IB Invasion equal to or more than half of the myometrium II Tumor invades cervical stroma, but does not extend beyond the uterus III Local and/or regional spread of the tumor IIIA Tumor invades the serosa of the corpus uteri and/or adnexae IIIB Vaginal and/or parametrial involvement IIIC Metastases to pelvic and/or para-aortic LN IIIC1 Positive pelvic LN IIIC2 Positive para-aortic LN with or without positive pelvic LN IV Tumor invades bladder and/or bowel mucosa, and/or distant metastases IVA Tumor invasion of bladder and/or bowel mucosa IVB Distant metastases, including intra-abdominal metastases and/or inguinal LN

  9. Surgical Approach Adjuvant Therapy Clinical assessment Surgical Staging Final Pathology

  10. ENDOMETRIAL CARCINOMA Preoperative Assessment RiskProfile CC inf. Histotype Lymphnode mets Grade Myometrial infiltration Extra-uterine spread Tumor diameter

  11. Overview on spread pattern in different EC subtypesAmant et al. Gynecol Oncol, 2005

  12. ENDOMETRIAL CARCINOMASerous Papillary/Clear Cell vs End G3 S.Greggi, Int J Gynecol Cancer (in press)

  13. Endometrial CarcinomaLymph nodal Status by M & G

  14. EC – Upgrading on Final PathologyPreop. G1-2 Endometrioid

  15. Identification of High Grade EC(Preop. End. Samples vs Final Pathology) Literature Review

  16. CARCINOMA ENDOMETRIALE Diagnostica per immagini - Accuratezza Karen, Genit Imaging 1999 Lara A, Genit Imaging 2000 Hardesty ,AJR 2001 Ruangvutilert, J Med Assoc Thai 2004 Manfredi, Rad 2004

  17. Endometrial Carcinoma Clinical Stage I Understaging 19-22 % Literature review

  18. CARCINOMA ENDOMETRIALE Diagnostica per immagini - Accuratezza Karen, 1999 Hardesty , 2001 Manfredi, 2004 Nagar, 2006

  19. END CA – Involvement of CCHysteroscopy Lo, 2001

  20. Analisys of EC Management North America & Western Europe Pre-surgicalNorth America Western Europe Staging n° of center (%) n° of center (%) Hysteroscopy Routinely used 3 (6%) 27 (33%) Usually omit 42 (87%) 47 (57%) Maggino et al, 1995-98

  21. SIOG– EC Management Survey(99 centers; 2008)

  22. EC - Parametrial Involvement (%)by FIGO Stage Pts undergoing Rad. or Mod. Rad. Hysterectomy * trans. cervix/param. +

  23. FIGO Stage II EC Outcome by Type of Hysterectomy

  24. CARCINOMA ENDOMETRIALE Diagnostica per immagini - Accuratezza Karen, Genit Imaging 1999 Connor Obstet Gynecol 2000 Manfredi, Rad 2004

  25. Nodal Status Assessment? • <10 % of +ve N are grossly enlarged (Creasman et al., Cancer 1987) • >50 % of +ve nodes < 1 cm (Girardi et al., Gynecol Oncol 1993) (Benedetti et al., Int J Gynecol Cancer 1998)

  26. 537 patients randomly assigned LIN.CE ILIADE-2 273 allocated Lymphadenectomy 264 allocated NO-Lymphadenectomy • 9 patients not eligible intra-operatively • Other histotype = 3 • Stage IA = 2 • Stage IB Grading 1 = 4 • 14 patients not eligible intra-operatively • Other histotype = 5 • Stage IA = 3 • Stage IB Grading 1 = 6 264 available for Intention To Treat Analysis 250 available for Intention To Treat Analysis 38 protocol violations (< 20 nodes resected) 17 protocol violations (≥20 nodes resected) 226 patients available for Per-Protocol Analysis 233 patients available for Per-Protocol Analysis

  27. Figure 3. Overall survival 90.0 85.9 events total ---- Lymphadenectomy 30 264 ___ No lymphadenectomy 23 250 % χ2=0.45; P=0.50 months Lymphad. 264 237 212 173 139 93 No lymph 250 226 193 160 125 93

  28. Figure 2. Disease free survival 81.7 81.0 events total ---- Lymphadenectomy 42 264 ___ No lymphadenectomy 36 250 % χ2=0.17; P=0.68 months Lymphad. 264 225 196 159 131 89 No lymph 250 218 184 150 114 85

  29. ENDOMETRIAL CANCER INT-NAPLES Jan 2001-June 2005 (No.110 Clinical Stage I Endometrioid EC Pts op. on) • BMI >= 35: 43 (39%) • ASA >=3: 30 (27%) • Uterus sized >12wks (and/or stenotic/deep vagina): • 15 (14%) • Potentially ineligible for LAVH: • 50 (45%)

  30. LAVH in Clinical Stage I EC Prospective Analysis – INT Naples (2005-07) (Endometrioid; Age<=70; BMI<35; ASA<3)

  31. GOG TRIAL LAP2 R A N D O M LAP-ASS VAGINAL SURGERY Endometrial ca or Ut. Sarcoma FIGO Stage I-IIa ABDOMINAL SURGERY Planned sample size: 2000; date of activation 1996

  32. Careful evaluation of general conditions Co-pathology & ASA Medical Operability Selection for LAVH /TLH

  33. S.I.O.G. - Indagine sulla Gestione Clinica del CE(99 centri; 2008)

  34. END. CANCER IN YOUNG WOMEN - is it possible to preserve fertility in young patients? - is it possible to achieve pregnancy in patients conservatively treated ?

  35. EC Pts Treated 1993-95. Distribution of Pts by Age Group and Mode of Staging 0,4% 2.5%

  36. EC < 40 year of Age Multivariate Analysis Factors Predicting Stage IA Duska, 2001

  37. Coexisting Ovarian Malignancies in EC Pts <45y-old

  38. G. Laurelli & S. Greggi, Gynecol Oncol (in press)

  39. CA ENDOMETRIALE RM addome-pelvi mdc CA 125 Rx Torace (2 pr) Val. Rischio Anestesiologico ASA >=3 T scarsamente diff. Istotipi Speciali Sospetta infiltrazione CC Sospetta/e metastasi LN Val. terapia conservativa Ospedale di II Livello Centro Riferimento Oncol

  40. Low-IntermediateRisk EC IA, G1-2, <2cm No benefit from LND or adjuvant RT Podratz, 1998; Keys, 2004 Adjuvant RT reduces local relapses, no impact on survival ESMO, 2009 Mariani, 2000

  41. Intermediate & High Risk / Early Stage

  42. Stage I - Endometrioid G1-2, >2cm G3 IB G1-2, IA, <2cm TH, BSO, Cyto TH, BSO, Cyto, pelvic LND pelvic N- pelvic N+ Ut Serosa /Adnexa + aortic LND aortic N- aortic N+ * No adjuvant CT + pelvic RT CT + pelvic/aortic RT

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