Carcinoma dell`Endometrio Cronoprogramma Diagnostico

Struttura Complessa di Ginecologia Oncologica
Direttore: Prof. Stefano Greggi
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%
CARCINOMA ENDOMETRIALE
Accuratezza stadiazione clinica
Chirurgia adeguata (isterectomia, linfoadenect., etc)
Terapie adiuvanti ( sovra-sottotrattamento)
Incremento sopravvivenza
Riduzione morbilità iatrogena
Migliore qualità della vita
da riferire urgentemente al Ginecologo
• Sanguinamento in post-menopausa (no TOS)
• Sanguinamento in post-menopausa (sospensione TOS
>=6 sett.)
• Sanguinamento in post-menopausa (Tamoxifene)
Perdite Ematiche
Atipiche
Eco Pelvi TV
Endometrio <4/5 mm
Rassicurante
HRT/TAM Endometrio
>8/10 mm
Endometrio >4/5 mm
Isteroscopia + biopsia endometriale
Normale
Rassicurante
Pat. Ben
Terapia
Cancro
Riferimento
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
EC - Scottish Pop-based Study
Staging Quality & Survival
(Crawford, 2002)
Surgeon Ctg
No. Pts
%
Non-specialist
616
88
Gynecol. Oncol.
87
12
1-19
493
70
<=20
199
30
FIGO doc.
PWs
p<.001
p<.0001
p<.0001
p<.002
Hospital Caseload
(no. EC pts/year)
79% of pts operated on by surgeons with <=5 EC pt caseload
Stadiazione FIGO (2009)
I
IA
IB
Tumor confined to the corpus uteri
No or less than half myometrial invasion
Invasion equal to or more than half of the myometrium
II
Tumor invades cervical stroma, but does not extend beyond the uterus
III
IIIA
IIIB
IIIC
IIIC1
IIIC2
Local and/or regional spread of the tumor
Tumor invades the serosa of the corpus uteri and/or adnexae
Vaginal and/or parametrial involvement
Metastases to pelvic and/or para-aortic LN
Positive pelvic LN
Positive para-aortic LN with or without positive pelvic LN
IV
IVA
IVB
Tumor invades bladder and/or bowel mucosa, and/or
distant metastases
Tumor invasion of bladder and/or bowel mucosa
Distant metastases, including intra-abdominal metastases and/or inguinal LN
Surgical
Approach
Clinical
assessmen
t
Surgical
Staging
Final Pathology
Adjuvant
Therapy
ENDOMETRIAL CARCINOMA
Preoperative Assessment
CC inf.
Risk Profile
Histotype
Lymphnode mets
Grade
Extra-uterine spread
Myometrial infiltration
Tumor diameter
Overview on spread pattern in different EC
subtypes
Amant et al. Gynecol Oncol, 2005
N (%)
Grade 3 E
Peritoneal Adnexa
cytology
86/668 (13) 41/721 (6)
Omentum
Pelvic LN
3/25 (12)
78/734 (11)
Ca.sarcom 72/373 (19) 75/512 (15) 15/96 (16)
a
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)
ENDOMETRIAL CARCINOMA
Serous Papillary/Clear Cell vs End G3
SP & CC
G3
63
76
28.6
7.9
28
19
M >50% (%)
58.3
64
Aneuploidia (%)
48.6
30.6
No Pts
IP mets (%)
N + (%)
S.Greggi, Int J Gynecol Cancer (in press)
Endometrial Carcinoma
Lymph nodal Status by M & G
% G1-G2
G3
P
A
P
A
M0
5-11
2
12
n.a.
M < 50%
7-9
2-3
16
7
M > 50%
1017
4-6
31
12
FIGO
EC – Upgrading on Final Pathology
Preop. 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
1204
21
Total
Identification of High Grade EC
(Preop. End. Samples vs Final Pathology)
% Missed
Reference centers
8-10
Overall
10-25
Literature Review
CARCINOMA ENDOMETRIALE
Diagnostica per immagini - Accuratezza
Infiltrazione Miometrio
Sensibilità
Specificità
US
69%
70.6%
TC
66-86%
66-75%
RM
78-100%
83-100%
Karen, Genit Imaging 1999
Lara A, Genit Imaging 2000
Hardesty ,AJR 2001
Ruangvutilert, J Med Assoc Thai 2004
Manfredi, Rad 2004
Endometrial Carcinoma
Clinical Stage I
Understaging
19-22 %
Literature review
CARCINOMA ENDOMETRIALE
Diagnostica per immagini - Accuratezza
Estensione alla Cervice
Sensibilità
Specificità
TC
20-70%
70-90%
RM
80-100%
96-100%
Karen, 1999
Hardesty , 2001
Manfredi, 2004
Nagar, 2006
END CA – Involvement of CC
Hysteroscopy
Hysteroscopy
No Pts
200
Accuracy (%)
92.5
PPV (%)
93.3
NPV (%)
92.4
Lo, 2001
Analisys of EC Management
North America & Western Europe
Pre-surgical
Staging
North America
n° of center (%)
Western Europe
n° of center (%)
Hysteroscopy
Routinely used
Usually omit
3 (6%)
27 (33%)
42 (87%)
47 (57%)
Maggino et al, 1995-98
SIOG – EC Management Survey
(99 centers; 2008)
% yes
Histeroscopy
IRCCS/University
92.9
90.5
Hospital
93.6
Nord
88.5
routine in preop staging
Centro-sud
100.0
<20 EC/y
93.6
>=20 EC/y
86.4
EC - Parametrial Involvement (%)
by FIGO Stage
Author
Yura
1996
Tamussino
2000
Sato
2003
Pts
91
Clin
St. I
Pathol
St. II St. I St. II St. III
Total
St. IV
-
-
0
11.5
52.9
-
13.2
-
8.3
-
9
-
-
41.6
16.9
100
5.9
Clin I-II
24
Clin II
269
16*
1.5
9.8
0
63
Clin I-III
Pts undergoing Rad. or Mod. Rad. Hysterectomy
* trans. cervix/param. +
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
CARCINOMA ENDOMETRIALE
Diagnostica per immagini - Accuratezza
Metastasi linfonodali
Sensibilità
Specificità
TC
57%
92%
RM
50%
95%
Karen, Genit Imaging 1999
Connor Obstet Gynecol 2000
Manfredi, Rad 2004
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)
537 patients randomly assigned
ILIADE-2
LIN.CE
273 allocated
264 allocated
Lymphadenectomy
NO-Lymphadenectomy
9 patients not eligible intraoperatively
14 patients not eligible
intra-operatively
•Other histotype = 3
•Stage IA = 2
•Stage IB Grading 1 = 4
•Other histotype = 5
•Stage IA = 3
•Stage IB Grading 1 = 6
264 available for
250 available for
Intention To Treat Analysis
Intention To Treat Analysis
38 protocol violations
17 protocol violations
(< 20 nodes resected)
(≥20 nodes resected)
226 patients available for
233 patients available for
Per-Protocol Analysis
Per-Protocol Analysis
Figure 3. Overall survival
100
90.0
85.9
80
60
%
40
events
total
---- Lymphadenectomy
30
264
___ No lymphadenectomy
23
250
20
χ2=0.45; P=0.50
0
0
6 12 18 24 30 36 42 48 54 60
months
Lymphad. 264
237
212
173
139
93
No lymph 250
226
193
160
125
93
Figure 2. Disease free survival
100
81.7
81.0
80
60
%
events
total
40
20
---- Lymphadenectomy
42
264
___ No lymphadenectomy
36
250
χ2=0.17; P=0.68
0
0
6 12 18 24 30 36 42 48 54 60
months
Lymphad. 264
225
196
159
131
89
No lymph 250
218
184
150
114
85
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%)
LAVH in Clinical Stage I EC
Prospective Analysis – INT Naples (2005-07)
(Endometrioid; Age<=70; BMI<35; ASA<3)
Variable
Potentially eligible for LAVH
LAVH performed
Previous LPTM
No.
%
34/61
23
12
55.7
100
52
Median Age (range)
Median BMI (range)
63 (52-70)
29 (26-30)
Pelvic LA
Aortic LA
No. Pelvic N
7
18 (12-28)
30
-
2
220 (160-330)
8.5
Converted to LPTM
Median OR time (min)
Lenght of Hospital stay (d)
3.5 (3-6)
GOG TRIAL LAP2
R
Endometrial
ca or Ut.
Sarcoma
FIGO Stage I-IIa
LAP-ASS VAGINAL SURGERY
A
N
D
O
M
ABDOMINAL SURGERY
Planned sample size: 2000; date of activation
1996
Careful evaluation of general conditions
Co-pathology & ASA
Medical
Operability
Selection for
LAVH /TLH
S.I.O.G. - Indagine sulla Gestione Clinica del CE
(99 centri; 2008)
Chirurgia elettiva St. I
%
Addominale
Vaginale
61.6
2.0
Totalmente lpsc
Vaginale lpsc-ass.
11.1
6.1
Add o Lpsc
17.2
Incl. Lpsc
Missing
34.4
2.0
END. CANCER IN YOUNG WOMEN
- is it possible to preserve fertility in
young patients?
- is it possible to achieve pregnancy
in patients conservatively treated ?
EC Pts Treated 1993-95.
Distribution of Pts by Age Group and Mode of Staging
0,4% 2.5%
EC < 40 year of Age
Multivariate Analysis
Factors Predicting Stage IA
Grade (1 vs 2-3)
OR
95% CI
16.8
(5.0 – 69)
Duska, 2001
Coexisting Ovarian Malignancies
in EC Pts <45y-old
Author
% <45y
% >45y
Gitsch, 1995
29
5
Evans-Metcalf
1998
11
2
G. Laurelli & S. Greggi, Gynecol Oncol (in press)
Case
Age
(years)
BMI
(Kg/m2)
Histotype
Grade
Hormone
Therapy
Relapse
(months)
1
41
24
E-G1
2
39
25
E-G1
Oral MA
Oral MA
No
No
3
38
26
E-G1
Oral MA
4
36
27
E-G1
5
37
31
6
38
7
Pregnancy
Follow-up (months) /
Current Status
No
79 / NED
No
77 / NED
No
No
68 / NED
Oral MA
No
62 / NED
E-G1
Oral MA
No
NFTD
No
25
E-G1
Oral MA
No
No
50 / NED
37
23
E-G1
No
No
43 / NED
8
39
28
E-G1
LNG-IUD
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
56 / NED
CA ENDOMETRIALE
RM addome-pelvi mdc
CA 125
Rx Torace (2 pr)
Val. Rischio Anestesiologico
ASA >=3
Ospedale di II Livello
T scarsamente diff.
Istotipi Speciali
Sospetta infiltrazione CC
Sospetta/e metastasi LN
Val. terapia conservativa
Centro Riferimento Oncol
Low-Intermediate Risk 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
Intermediate & High Risk / Early Stage
Stage I - Endometrioid
G1-2, IA, <2cm
G1-2, >2cm
G3
IB
TH, BSO, Cyto
TH, BSO, Cyto, pelvic LND
pelvic N-
pelvic N+
Ut Serosa /Adnexa +
aortic LND
aortic NNo adjuvant
CT + pelvic RT
aortic N+ *
CT + pelvic/aortic RT