carcinoma dellendometrio cronoprogrammadiagnostico-terapeutico
TRANSCRIPT
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Carcinoma dell’EndometrioCarcinoma dell’EndometrioCronoprogramma Cronoprogramma
Diagnostico-TerapeuticoDiagnostico-Terapeutico
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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 ENDOMETRIALE
Accuratezza stadiazione clinica
Chirurgia adeguata (isterectomia, linfoadenect., etc)
Terapie adiuvanti ( sovra-sottotrattamento)
Incremento sopravvivenzaRiduzione morbilità iatrogena
Migliore qualità della vita
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da riferire urgentemente al Ginecologo
• Sanguinamento in post-menopausa (no TOS)
• Sanguinamento in post-menopausa (sospensione TOS >=6 sett.)
• Sanguinamento in post-menopausa (Tamoxifene)
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Perdite Ematiche Atipiche
Eco Pelvi TV
Endometrio <4/5 mm Endometrio >4/5 mm
RassicuranteIsteroscopia + biopsia endometriale
Normale Pat. Ben Cancro
Rassicurante Terapia Riferimento
HRT/TAM Endometrio >8/10 mm
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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
!
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EC - Scottish Pop-based StudyStaging Quality & Survival
(Crawford, 2002)
Surgeon Ctg No. Pts % FIGO doc. PWs
Non-specialist 616 88
Gynecol. Oncol. 87 12 p<.001 p<.0001
Hospital Caseload
(no. EC pts/year)
1-19 493 70
<=20 199 30 p<.0001 p<.002
79% of pts operated on by surgeons with <=5 EC pt caseload
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Stadiazione FIGO (2009)Stadiazione FIGO (2009)
II Tumor confined to the corpus uteriTumor confined to the corpus uteri
IAIA No or less than half myometrial invasionNo or less than half myometrial invasion
IBIB Invasion equal to or more than half of the myometriumInvasion equal to or more than half of the myometrium
IIII Tumor invades cervical stroma, but does not extend beyond the uterusTumor invades cervical stroma, but does not extend beyond the uterus
IIIIII Local and/or regional spread of the tumorLocal and/or regional spread of the tumor
IIIAIIIA Tumor invades the serosa of the corpus uteri and/or adnexaeTumor invades the serosa of the corpus uteri and/or adnexae
IIIBIIIB Vaginal and/or parametrial involvementVaginal and/or parametrial involvement
IIICIIIC Metastases to pelvic and/or para-aortic LNMetastases to pelvic and/or para-aortic LN
IIIC1IIIC1 Positive pelvic LNPositive pelvic LN
IIIC2IIIC2 Positive para-aortic LN with or without positive pelvic LNPositive para-aortic LN with or without positive pelvic LN
IVIV Tumor invades bladder and/or bowel mucosa, and/or Tumor invades bladder and/or bowel mucosa, and/or distant metastasesdistant metastases
IVAIVA Tumor invasion of bladder and/or bowel mucosaTumor invasion of bladder and/or bowel mucosa
IVBIVB Distant metastases, including intra-abdominal metastases and/or inguinal LNDistant metastases, including intra-abdominal metastases and/or inguinal LN
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Clinical assessment
Surgical Staging
Surgical Approach
Adjuvant TherapyFinal Pathology
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ENDOMETRIAL CARCINOMA
Preoperative Assessment
Histotype
Grade
Myometrial infiltration
Risk ProfileRisk Profile
Extra-uterine spread
Lymphnode mets
CC inf.
Tumor diameter
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Overview on spread pattern in different EC Overview on spread pattern in different EC subtypessubtypes
Amant et al. Gynecol Oncol, 2005Amant et al. Gynecol Oncol, 2005
N (%) Peritoneal cytology
Adnexa Omentum Pelvic LN
Grade 3 E 86/668 (13) 41/721 (6) 3/25 (12) 78/734 (11)
Ca.sarcoma
72/373 (19) 75/512 (15) 15/96 (16) 80/423 (19)
Serous pap.
17/57 (13) 27/125 (22) 47/202 (23) 72/244 (30)
Clear cell 7/20 (35) 3/32 (9) 3/6 (50) 9/20 (45)
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ENDOMETRIAL CARCINOMASerous Papillary/Clear Cell vs End G3
SP & CC G3
No Pts 63 76
IP mets (%) 28.6 7.9
N + (%) 28 19
M >50% (%) 58.3 64
Aneuploidia (%) 48.6 30.6
S.Greggi, Int J Gynecol Cancer (in press)
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Endometrial CarcinomaLymph nodal Status by M & G
% G1-G2 G3
P A P A
M 0 5-11 2 12 n.a.
M < 50% 7-9 2-3 16 7
M > 50% 10-17
4-6 31 12
FIGO
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EC – Upgrading on Final PathologyPreop. G1-2 Endometrioid
Author No. Pts % Upgraded
Daniel, 1988 205 14
Malviya, 1989 55 11
Stovall, 1991 39 13
Larson, 1995 145 27
Obermair, 1999 137 21
Frumovitz, 2004 153 24
Eltabbakh, 2005 182 29
Ben-Schacher, 2005 181 19
Case, 2006 43 44
Traen, 2007 64 3
Total 1204 21
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Identification of High Grade EC(Preop. End. Samples vs Final Pathology)
% Missed
Reference centers 8-10
Overall 10-25
Literature Review
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CARCINOMA ENDOMETRIALEDiagnostica per immagini - Accuratezza
Infiltrazione Miometrio
Sensibilità Specificità
US 69% 70.6%
TC 66-86% 66-75%
RM 78-100% 83-100%
Karen, Genit Imaging 1999Lara A, Genit Imaging 2000Hardesty ,AJR 2001Ruangvutilert, J Med Assoc Thai 2004Manfredi, Rad 2004
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Clinical Stage I
Understaging
19-22 %
Endometrial Carcinoma
Literature review
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CARCINOMA ENDOMETRIALEDiagnostica per immagini - Accuratezza
Estensione alla Cervice
Sensibilità Specificità
TC 20-70% 70-90%
RM 80-100% 96-100%
Karen, 1999Hardesty , 2001Manfredi, 2004Nagar, 2006
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END CA – Involvement of CCHysteroscopy
Hysteroscopy
No Pts 200
Accuracy (%) 92.5
PPV (%) 93.3
NPV (%) 92.4
Lo, 2001
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Analisys of EC Management North America & Western Europe
Pre-surgical North America Western EuropeStaging n° of center (%) n° of center (%)
Hysteroscopy
Routinely used 3 (6%)
27 (33%)
Usually omit 42 (87%)
47 (57%)
Maggino et al, 1995-98
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SIOG – EC Management Survey(99 centers; 2008)
% yes
Histeroscopyroutine in preop staging 92.9
IRCCS/University 90.5
Hospital 93.6
Nord 88.5
Centro-sud 100.0
<20 EC/y 93.6
>=20 EC/y 86.4
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EC - Parametrial Involvement (%)by FIGO Stage
Author Pts Clin
St. I St. II
Pathol
St. I St. II St. III St. IV
Total
Yura
1996
91Clin I-II
- - 0 11.5 52.9 - 13.2
Tamussino
2000
24Clin II
- 8.3 - 9
16*
- - 41.6
Sato
2003
269Clin I-III
1.5 9.8 0 63 16.9 100 5.9
Pts undergoing Rad. or Mod. Rad. Hysterectomy * trans. cervix/param. +
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FIGO Stage II EC Outcome by Type of Hysterectomy
Author No. % 5y PFS
SH RH p
% 5y OS
SH RH p
Mariani, 2001 203 73 100 .01 80 100 .01
Cohn, 2007 160 76 94 .05 - - -
Cornelison,1999 932 - - - 84 93 .05
Sartori, 2001 203 - - - 79 94 .03
Ayhan, 2004 48 81 85 NS 83 90 NS
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CARCINOMA ENDOMETRIALEDiagnostica per immagini - Accuratezza
Metastasi linfonodali
Sensibilità Specificità
TC 57% 92%
RM 50% 95%
Karen, Genit Imaging 1999Connor Obstet Gynecol 2000Manfredi, Rad 2004
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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)
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537 patients randomly assigned
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 = 6264 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
ILIADE-2 LIN.CE
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0
20
40
60
80
100
0 6 12 18 24 30 36 42 48 54 60
monthsmonths
%%
χ2=0.45; P=0.50
events total
---- Lymphadenectomy 30 264
___ No lymphadenectomy 23 250
Lymphad. 264 237 212 173 139 93
No lymph 250 226 193 160 125 93
Figure 3. Overall survival
90.0
85.9
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0
20
40
60
80
100
0 6 12 18 24 30 36 42 48 54 60
monthsmonths
%%
χ2=0.17; P=0.68
eventstotal
---- Lymphadenectomy 42 264
___ No lymphadenectomy 36 250
Lymphad. 264 225 196 159 131 89
No lymph 250 218 184 150 114 85
Figure 2. Disease free survival
81.7
81.0
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ENDOMETRIAL CANCERINT-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%)
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Variable No. %
Potentially eligible for LAVH LAVH performed Previous LPTM
34/612312
55.710052
Median Age (range)Median BMI (range)
63 (52-70)29 (26-30)
Pelvic LAAortic LANo. Pelvic N
7-
18 (12-28)
30-
Converted to LPTMMedian OR time (min)
2220 (160-330)
8.5
Lenght of Hospital stay (d)
3.5 (3-6)
LAVH in Clinical Stage I ECProspective Analysis – INT Naples (2005-07)(Endometrioid; Age<=70; BMI<35; ASA<3)
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R
A
N
D
O
M
LAP-ASS VAGINAL SURGERY
ABDOMINAL SURGERY
GOG TRIAL LAP2
FIGO Stage I-IIa
Endometrial ca or Ut. Sarcoma
Planned sample size: 2000; date of activation 1996
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Careful evaluation of general conditionsCo-pathology & ASA
Medical Operability
Selection forLAVH /TLH
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S.I.O.G. - Indagine sulla Gestione Clinica del CE(99 centri; 2008)
Chirurgia elettiva St. I %Addominale 61.6
Vaginale 2.0
Totalmente lpsc 11.1
Vaginale lpsc-ass. 6.1
Add o Lpsc 17.2
Incl. Lpsc 34.4
Missing 2.0
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END. CANCER IN YOUNG WOMEN
- is it possible to preserve fertility in
young patients?
- is it possible to achieve pregnancy
in patients conservatively treated ?
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EC Pts Treated 1993-95.
Distribution of Pts by Age Group and Mode of Staging
0,4% 2.5%
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EC < 40 year of Age
Multivariate Analysis
Factors Predicting Stage IA
OR 95% CI
Grade (1 vs 2-3) 16.8 (5.0 – 69)
Duska, 2001
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Coexisting Ovarian Malignancies in EC Pts <45y-old
Author % <45y % >45y
Gitsch, 1995 29 5
Evans-Metcalf 1998
11 2
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CaseAge
(years)BMI
(Kg/m2)
HistotypeGrade
HormoneTherapy
Relapse(months)
PregnancyFollow-up (months) /
Current Status
1 41 24 E-G1 Oral MA No No 79 / NED
2 39 25 E-G1 Oral MA No No 77 / NED
3 38 26 E-G1 Oral MA No No 68 / NED
4 36 27 E-G1 Oral MA No NFTD 62 / NED
5 37 31 E-G1 Oral MA No No 56 / NED
6 38 25 E-G1 Oral MA No No 50 / NED
7 37 23 E-G1 LNG-IUD No No 43 / NED
8 39 28 E-G1 LNG-IUD No No 37 / NED
9 39 26 E-G1 LNG-IUD No No 30 / NED
10 39 48 E-G1 LNG-IUD No No 28 / NED
11 37 23 E-G1 LNG-IUD No No 26 / NED
12 40 24 E-G1 LNG-IUD No No 19 / NED
13 28 53 E-G1 LNG-IUD Yes No 17 / NED
14 26 27 E-G1 LNG-IUD No No 13 / NED
G. Laurelli & S. Greggi, Gynecol Oncol (in press)
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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
Centro Riferimento Oncol
Ospedale di II Livello
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Low-Intermediate Risk ECLow-Intermediate Risk EC
Mariani, 2000Mariani, 2000
No benefit from LND or adjuvant RTNo benefit from LND or adjuvant RT
Podratz, 1998; Keys, 2004 Podratz, 1998; Keys, 2004
Adjuvant RT reduces local relapses, no impact on survival Adjuvant RT reduces local relapses, no impact on survival
ESMO, 2009ESMO, 2009
IA, G1-2, <2cmIA, G1-2, <2cm
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Intermediate & High Risk / Early StageIntermediate & High Risk / Early Stage
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Stage I - Endometrioid Stage I - Endometrioid
G1-2, IA, <2cmG1-2, >2cm
G3IB
TH, BSO, Cyto TH, BSO, Cyto, pelvic LND
pelvic N- pelvic N+ Ut Serosa /Adnexa +
aortic N+ *
No adjuvant CT + pelvic RT CT + pelvic/aortic RT
aortic N-
aortic LND