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Endometriumkarzinom - Diagnose und Therapie C Tempfer.

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Präsentation zum Thema: "Endometriumkarzinom - Diagnose und Therapie C Tempfer."—  Präsentation transkript:

1 Endometriumkarzinom - Diagnose und Therapie C Tempfer

2 Allgemeines n Häufigstes Malignom - Genitaltrakt n 31 000 neue Fälle/5400 Todesfälle pro Jahr n hohe Prävalenz – westl. Industriestaaten n geringe Prävalenz - Entwicklungsländer, Südasien, Indien n Östrogen-abhängig –ERT, BMI, Ernährung, anovulatorische Zyklen –Alter/Postmenopause, ger. Parität, hoher Sozialstatus

3 PAP Test PAP Test n Kein Screening-Test für Endometriumkarzinom n Sensitivität 50% (rp/k) –50% aller Frauen mit EK zeigen abnormale Endometriumzellen im Abstrich n Spezifität 25% (rp/pt) –75% falsch positiv

4 TVS – N. endometrii  n=5013; TVS-Doppler  N. endometrii stage I: 6 (Kurjak 1994) n=1000; TVS n=1000; TVS 4mm cut-off; N. endometrii stage I: 1 (Karlsson 1996)4mm cut-off; N. endometrii stage I: 1 (Karlsson 1996) n=1074; TVS+Doppler n=1074; TVS+Doppler  4mm cut-off/PI; N. endometrii stage I: 3 (Vuento 1999)  n=2025; TVS  N. endometrii: 3 (Ciatto 1995) Summe: 9112/13; NNS 701

5 Screening Screening n Kein etabliertes Massenscreening –Kein adäquater Bluttest, kein Tumormarker –Keine ideale sampling-Methode n Hochrisikopopulationen –Tamoxifen –Lynch II/HNPCC

6 TVS und TAM  Gerber 2000; n=247; 10mm cut-off; 5a; 1 asymptomatic cancer; 52 D&Cs; 4 perfor.  Love 1999; n=487; 5mm cut-off; 0 cancers; 134 D&Cs  Fung 2003; 9mm cut-off; 304 D&Cs - 6 cancers-all with bleeding 1/525 D&C

7 n TVS – 2 Studien (Rijcken 2003; Dove 2002) n n=41; 5 yrs; 17/179 TVS positive: 3 atyp. Hyperpl.; 1 Ca nicht entdeckt n n=269; 3 yrs; 2 Endometrium-Ca; 0/2 durch TVS n TVS + CA 125 - keine Daten n TVS + endometrial sampling –1 Studie (Renkonen 2006) n n=175; 5 yrs; 11/14 entdeckt (8 durch Biopsie) + 14 atypische Hyperplasien; 0/4 N. ovarii entdeckt HNPCC

8 Empfehlung n Empfehlung American Cancer Society, US Preventive Task Force –‚…annual screening with endometrial biopsy beginning at age 35‘ Smith et al. ACS guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006;56:11-25

9 Klinik n Persist. perimenopausale Blutung n Hämatometra/Pyometra in Postm. n PMB –endometrial cancer: 15% of PMB - specificity 15% –90% of women with endometrial cancer - sensitivity 90% (Hacker et al. 1986)

10 Diagnose n Histologie 1) Endometrium-Biopsie (Pipelle®, Kevorkian-Curette) 2) D&C 3) advanced stage disease – LAP/LSK

11 –65 Studien, n=26 346 (Clark et al. 2002) –Sensitivität 86.4% Spezifität 99.2% –13.7% of cancers will be missed –post-test LR 0.15 not low enough to negate need for further testing –ERSETZT NICHT ABRASIO –zusätzlich zu Abrasio? - keine Daten Hysteroskopie

12 Hysteroskopie n Upstaging? Prognose? n 10/113 (9%) pos. periton. Zytologie (Obermair et al. 2000) – FIGO IIIa n n=262, Ia, Ib +/- HSK –assoziiert mit HSK (p=0.04), nicht Stadium, Grading, Histologie n n=123; CO2 1.4% vs. saline 14%; p=0.0009 (Lo et al. 2002) n 5-yr DFS, n=135+HSK; 127-HSK: 92.4% vs. 84.7% (p=0.5) (Obermair et al. 2000)

13 Endometriumhyperplasie Endometriumhyperplasie n 2 unterschiedliche Entitäten –+/- Atypien (Kurman 1985) n Risiko Progression 1.6% vs. 23% (Kurman 1985; n=170) n Ansprechen auf MPA 94% vs. 50% (Ferenczy 1989; n=85) 1) Die meisten Frauen mit EMH ohne Atypien sprechen auf MPA an 2) Hysterektomie: Atypien, non-Responder MPA

14 Endometriumhyperplasie Endometriumhyperplasie n Konkomitantes Karzinom –n=54; EMH+Atypien, HE (Hunter 1994) n Karzinom 19/54 (35%) –n=46; EMH+Atypien, HE (Bilgin 2004) n Karzinom 11/46 (24%) –n=289; EMH+Atypien, HE (Trimble 2006) n Karzinom 123/289 (43%)

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17 Biologie n Ausbreitungsrouten –Direkte Extension - häufigste –lymphatisch - pelvin/paraaortal –hämatogen - Lunge –Tube - Hysteroskopie

18 Staging þ Surgically staged disease (FIGO 1988) þreplaced clinical staging system (1971) þ Unterschied? þsignificant understaging (Tiitinen 1986)

19 Staging (FIGO 1988) I - corpus Ia - endometrium; Ib/Ic - 50% myometrium II - cervix III -extrauterine spread IIIa - serosa/adnexae/pos. washing, IIIb - vagina, IIIc -nodes IV - bladder or distant

20 Verteilung nach Stadium Tumor StageNumber (n)Percent (%) I573074.8 II 87111.4 III 81810.7 IV 227 2.9 No Stage 17 0.2 Total 7663 100.0

21 Pelvine Lymphknotenmetastasen Depth of Inv.G1 (n=180)G2 (n=288) G3 (n=153) Endometrium 0 (0%) 1 (3%) 0 (0%) Inner Third 3 (3%) 7 (5%) 5 (9%) Middle Third 0 (0%) 6 (9%) 1 (4%) Outer Third 2 (11%) 11 (19%) 22 (34%) Creasman et al. 1987

22 Lnn-Metastasen - Tumorgrösse Depth of Inv. 2cm (%) Surf. (%) None 0/17 (0) 0/8 (0) 0/0 (0) <50% 0/27 (0) 5/41 (12) 2/9 (22) >50% 2/9 (22) 6/23 (26) 4/8 (50) Schink et al. 1987

23 Paraaortale Lnn-Metastasen Depth of Inv.G1 (n=180)G2 (n=288) G3 (n=153) Endometrium 0 (0%) 1 (3%) 0 (0%) Inner Third 1 (1%) 5 (4%) 2 (4%) Middle Third 1 (5%) 0 (0%) 0 (0%) Outer Third 1 (6%) 8 (14%) 15 (23%) Creasman et al. 1987

24 Prognosefaktoren n Alter –young women better prognosis (stage, grading) n Histo 52/388 (13%) (Wilson 1990) n adenosquamous, clear cell, USPC, undifferentiated n 33% vs. 92% 5-yr OS n Stadium, Grading, LVSI n Spülzytologie+: 10.8%-22% (7 studies, n=1541) n ER+, PR+ better prognosis (Palmer et al. 1988) n DNA-Ploidie aneuploid worse prognosis

25 Treatment Stage I þ Abdominal washing þ Total abdominal hysterectomy and bilateral oophorectomy (TAH-BSO) þ full pelvic lymphadenectomy þ >50% (Ic), poor histology, G3, G2>2cm, stage II þ paraaortic lymphadenectomy? þG2/3 outer third invasion, grossly positive pelvic nodes or adnexae, palp. paraaortic nodes (GOG-study, Morrow 1991)

26 Therapie I þ Adjuvant irradiation does not improve OS þ Adjuvant irradiation improves local control þvault irrad. recurrences: 14%-1.7% (Lotocki 1983) þpelvic irrad. G3, Ic, II, pN+ þextended field irrad. G2/3+outer third, aN+, multiple pN+ þwhole adominal irrad. perit., oment. metast., +cytology?

27 PORTEC þ n=715; Stadium I (G1 Ic, G2, G3 Ib) þ adjuvant pelvic irradiation vs. no therapy þ no lymphadenectomy; 46 Gray þ Lokalrezidive 4 vs. 14% (p<0.001) þ 5-YOS: 81 vs. 85% (p=n.s.) þ complications: 25 vs. 6% þ keine adjuvante Bestrahlung þ Prädiktiver Faktor: Alter >60yrs

28 PORTEC þ G1 Ia,b.........................keine Irrad þ G1 Ic, G2 Ib..................Irrad >60 yrs þ G2 Ic, G3………….………..Irrad þ pelvic irradiation þ G1 Ia, Ib, G1 Ic <60 yrs, G2 Ib <60 yrs þ vaginal vault irradiation

29 þ Stage II: surgery, combined radiation/surgery, Wertheim-procedure þ Stage III: surgical removal of all macroscopic tumor þ Stage IV: combination þsurgery: local control - palliation, bowel; exenteration (sole bladder or rectum involvement) þirradiation, progestins: 10% CR, 28% PR (Thigpen 1986; n=331) þchemotherapy: Carbo/Taxol Therapie II

30 Prognose 5-Jahres Überleben GradeStage (%) Ia Ib Ic IIaIIb 192.3 94.1 83.2 86.172.7 289.7 84.9 79.8 71.871.1 381.5 76.3 68.3 65.949.0 Stage III-IV: 5-Year OS rates 0%-16% (Aalders 1984) Stage III ovary/tube only: 80% 5-Year OS (Bruckman 1980)

31 UPSC/CCC/recurrent

32 UPSC/CCC/recurrent

33 Serös-papillär n Prognosis, treatment n 50% of all relapses caused by UPSC & CC n subsequent breast cancer: 3.2% vs. 25% (Geisler et al. 2001) n paclitaxel - III, IV, recurrent; n=20 (Ramondetta et al. 2001) –OR rate 77%; med. time to progess. 7.3 mos n treat equivalent to ovarian cancer (Carbo/Taxol)


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