Exercise in Pregnancy

Endometriumkarzinom Diagnose und Therapie
C Tempfer
Allgemeines

Häufigstes Malignom - Genitaltrakt




31 000 neue Fälle/5400 Todesfälle pro Jahr
hohe Prävalenz – westl. Industriestaaten
geringe Prävalenz - Entwicklungsländer,
Südasien, Indien
Östrogen-abhängig
– ERT, BMI, Ernährung, anovulatorische Zyklen
– Alter/Postmenopause, ger. Parität, hoher Sozialstatus
PAP Test
Kein Screening-Test für
Endometriumkarzinom
 Sensitivität 50% (rp/k)
– 50% aller Frauen mit EK zeigen
abnormale Endometriumzellen im
Abstrich
 Spezifität 25% (rp/pt)
– 75% falsch positiv

TVS – N. endometrii
 n=5013;
•
•
TVS-Doppler
N. endometrii stage I: 6 (Kurjak 1994)
n=1000; TVS
• 4mm cut-off; N. endometrii stage I: 1 (Karlsson 1996)
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
Screening

Kein etabliertes Massenscreening
– Kein adäquater Bluttest, kein Tumormarker
– Keine ideale sampling-Methode

Hochrisikopopulationen
– Tamoxifen
– Lynch II/HNPCC
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
HNPCC

TVS
– 2 Studien




(Rijcken 2003; Dove 2002)
n=41; 5 yrs; 17/179 TVS positive: 3 atyp. Hyperpl.; 1
Ca nicht entdeckt
n=269; 3 yrs; 2 Endometrium-Ca; 0/2 durch TVS
TVS + CA 125 - keine Daten
TVS + endometrial sampling
– 1 Studie

(Renkonen 2006)
n=175; 5 yrs; 11/14 entdeckt (8 durch Biopsie) + 14
atypische Hyperplasien; 0/4 N. ovarii entdeckt
Empfehlung

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
Klinik
 Persist.
perimenopausale Blutung
 Hämatometra/Pyometra in Postm.
 PMB
– endometrial cancer: 15% of PMB specificity 15%
– 90% of women with endometrial cancer sensitivity 90% (Hacker et al. 1986)
Diagnose
 Histologie
1) Endometrium-Biopsie (Pipelle®,
Kevorkian-Curette)
2) D&C
3) advanced stage disease – LAP/LSK
Hysteroskopie
– 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
 Upstaging?
Prognose?
10/113 (9%) pos. periton. Zytologie (Obermair
et al. 2000) – FIGO IIIa
 n=262, Ia, Ib +/- HSK
–assoziiert mit HSK (p=0.04), nicht
Stadium, Grading, Histologie
 n=123; CO2 1.4% vs. saline 14%; p=0.0009

(Lo et al. 2002)

5-yr DFS, n=135+HSK; 127-HSK: 92.4% vs.
84.7% (p=0.5) (Obermair et al. 2000)
Endometriumhyperplasie
2
unterschiedliche Entitäten
– +/- Atypien

(Kurman 1985)
Risiko Progression 1.6% vs. 23%
(Kurman 1985; n=170)

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
Endometriumhyperplasie
 Konkomitantes
Karzinom
– n=54; EMH+Atypien, HE

Karzinom 19/54 (35%)
– n=46; EMH+Atypien, HE

(Hunter 1994)
(Bilgin 2004)
Karzinom 11/46 (24%)
– n=289; EMH+Atypien, HE

(Trimble 2006)
Karzinom 123/289 (43%)
Biologie
 Ausbreitungsrouten
–Direkte Extension - häufigste
–lymphatisch - pelvin/paraaortal
–hämatogen - Lunge
–Tube - Hysteroskopie
Staging
Surgically staged disease (FIGO 1988)
replaced clinical staging system (1971)
Unterschied?
significant understaging
(Tiitinen 1986)
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
Verteilung nach Stadium
Tumor Stage
Number (n)
I
II
III
IV
No Stage
Total
5730
871
818
227
17
7663
Percent (%)
74.8
11.4
10.7
2.9
0.2
100.0
Pelvine Lymphknotenmetastasen
Depth of Inv.
Endometrium
Inner Third
Middle Third
Outer Third
Creasman et al. 1987
G1 (n=180) G2 (n=288)
0
3
0
2
(0%)
(3%)
(0%)
(11%)
1 (3%)
7 (5%)
6 (9%)
11 (19%)
G3 (n=153)
0 (0%)
5 (9%)
1 (4%)
22 (34%)
Lnn-Metastasen - Tumorgrösse
Depth of Inv.
None
<50%
>50%
Schink et al. 1987
<2cm (%)
>2cm (%)
Surf. (%)
0/17 (0)
0/27 (0)
2/9 (22)
0/8 (0)
5/41 (12)
6/23 (26)
0/0 (0)
2/9 (22)
4/8 (50)
Paraaortale Lnn-Metastasen
Depth of Inv.
Endometrium
Inner Third
Middle Third
Outer Third
Creasman et al. 1987
G1 (n=180) G2 (n=288)
0
1
1
1
(0%)
(1%)
(5%)
(6%)
1
5
0
8
(3%)
(4%)
(0%)
(14%)
G3 (n=153)
0 (0%)
2 (4%)
0 (0%)
15 (23%)
Prognosefaktoren






Alter
– young women better prognosis (stage, grading)
Histo 52/388 (13%) (Wilson 1990)
 adenosquamous, clear cell, USPC,
undifferentiated
 33% vs. 92% 5-yr OS
Stadium, Grading, LVSI
Spülzytologie+: 10.8%-22% (7 studies, n=1541)
ER+, PR+ better prognosis (Palmer et al. 1988)
DNA-Ploidie aneuploid worse prognosis
Treatment Stage I
Abdominal washing
Total abdominal hysterectomy and bilateral
oophorectomy (TAH-BSO)
full pelvic lymphadenectomy
 >50% (Ic), poor histology, G3, G2>2cm, stage II
paraaortic lymphadenectomy?
G2/3 outer third invasion, grossly positive pelvic nodes
or adnexae, palp. paraaortic nodes (GOG-study, Morrow
1991)
Therapie I
Adjuvant irradiation does not improve OS
Adjuvant irradiation improves local control
vault irrad. recurrences: 14%-1.7% (Lotocki 1983)
pelvic irrad. G3, Ic, II, pN+
extended field irrad. G2/3+outer third, aN+,
multiple pN+
whole adominal irrad. perit., oment. metast.,
+cytology?
PORTEC
n=715; Stadium I (G1 Ic, G2, G3 Ib)
adjuvant pelvic irradiation vs. no therapy




no lymphadenectomy; 46 Gray
Lokalrezidive 4 vs. 14% (p<0.001)
5-YOS: 81 vs. 85% (p=n.s.)
complications: 25 vs. 6%
keine adjuvante Bestrahlung
Prädiktiver Faktor: Alter >60yrs
PORTEC
G1 Ia,b.........................keine Irrad
G1 Ic, G2 Ib..................Irrad >60 yrs
G2 Ic, G3………….………..Irrad
pelvic irradiation
G1 Ia, Ib, G1 Ic <60 yrs, G2 Ib <60 yrs
vaginal vault irradiation
Therapie II
Stage II: surgery, combined
radiation/surgery, Wertheim-procedure
Stage III: surgical removal of all
macroscopic tumor
Stage IV: combination
surgery: local control - palliation, bowel; exenteration
(sole bladder or rectum involvement)
irradiation, progestins: 10% CR, 28% PR (Thigpen 1986;
n=331)
chemotherapy: Carbo/Taxol
Prognose 5-Jahres Überleben
Grade
1
2
3
Ia
Ib
92.3
89.7
81.5
94.1
84.9
76.3
Stage (%)
Ic
IIa
83.2
79.8
68.3
86.1
71.8
65.9
IIb
72.7
71.1
49.0
Stage III-IV: 5-Year OS rates 0%-16% (Aalders 1984)
Stage III ovary/tube only: 80% 5-Year OS (Bruckman
1980)
UPSC/CCC/recurrent
UPSC/CCC/recurrent
Serös-papillär
 Prognosis,
treatment
50% of all relapses caused by UPSC & CC
 subsequent breast cancer: 3.2% vs. 25%

(Geisler et al. 2001)

paclitaxel - III, IV, recurrent; n=20
(Ramondetta et al. 2001)
–OR rate 77%; med. time to progess. 7.3
mos
 treat equivalent to ovarian cancer
(Carbo/Taxol)