Transcript Slide 1

Fertility Sparing Surgery (FSS) in
Gynecologic Oncology
Ali AYHAN, MD.
Baskent University School of Medicine Department of Obstetrics &
Gynecology Division of Gynecologic Oncology
The Main Purpose of Cancer
Therapy
• High cure
• Low morbidity
• High level of quality of life
(as a mood, sexuel life,
cosmetic appearence,
fertility preservation...)
All Therapeutic Modalities in
Female Cancer
Are associated with
infertility
(radiation, radical surgery,
chemo...)
Therefore
Fertility saving surgery instead of
radical in early stage selected
gyn/cancer
is performed by different centers
FSS Objectives
• Similiar oncologic outcomes
to standard therapy
• Favorable obstetric
outcome
• Benefits > risks
• Low morbidity and cost
Benefits-Risks of FSS
Benefits
• Preservation
of fertility
• Maintanence
of endocrine
function
Risks
• Increase in
probability of
recurrence and
death
• Additional
surgery
The Main Requirement of FSS
Preserving of the uterus
Preserving at least one
ovary
Fertility Saving Surgery
Depends on
• Type and origions of tumor
• Stage, grade, histology
• Age, performance
• Fertility desire
• Previous infertility problems
• Close follow up
Indications for Fertility Saving
Surgery
• All germ cell
• Sex cord stromal (early stage)
• Borderline ovarian tumor
• Invasive EOC
• Cervical Carcinoma
• Endometrial Carcinoma
Fertility Saving Surgery in Ovarian Tumors
(EOC, BOT,MOGCT, Sex Cord Stromal)
• Adequate surgical staging
• Removal of affected ovary and tube
• Preservation of uterus and
contralateral ovary
• Finally evaluation of normal
appearing contralateral ovary* and
endometrium (D&C)**
* For occult metastases
* Endometrioid type of epithelial tumors
FSS in EOC
• 25-30% of all EOC are early stage at
the diagnosis
• 14% of EOC will occur under 40
years
• Of these 62% will be stage I and IIa
• Not all, many of these desire to
preserve fertility
SO TODAY; PROBLEM IS SMALL
Indication for Fertility Sparing
Surgery in EOC
1. Stage Ia Grade 1
Stage Ia Grade 2 (limited)
2. Stage Ic, Grade 3, Clear cell
+
Chemotherapy
Main Problems in FSS in EOC
A) In preserved ovary
1) occult metastasis
2) Relapse in spared ovary
B) Is there any relationship between
relapse, death and preservation of
ovary, uterus or other risk factors
C) Is there a place of complementary
surgery after childbearing
Occult Metastasis in Normal
Appearing Ovaries
• Varies from 7-33% in old
literature
• In new literature, this
figures are lower than
older (about 2.5%)
Survival
925 patients with early stage disease
were subjected to Radical Surgery
+Chemo
(ICON1 and ACTION Studies)
5 yrs DFS
5 yrs OS
76%
82%
J Natl Cancer Inst, 2003:95:105-112
FSS Does Not Affect Survival in
Early Stage EOC
• Survival after FSS in patients
with early ovarian cancer
• Without chemo is about 94%
Recurrence, Death and
Pregnancy After FSS in EOC
Author
Colombo
n=152
Brown
n=16
Schilders
n=52
UK Study
n=56
Recurrences
Deaths
Ovary / Total
11 /18
9 (5.9%)
Pregnancy
53 (35%)
2/2
2
?
3/5
2
26
12%
0
?
Colombo N et al IJGC 2005, Monk BJ, DiSaia PJ, IJGC 2005, Farthing A, BJOG 2006
Obstetric Outcome After Fertility
Saving Surgery in EOC
Author
% Pregnancy
Colombo 100 (25/25)
1994
Term
Delivery
Abort.
Ectopic
Anomaly
16
17
2
4
4
0
2
2
1
0
0
0
Zanetta
1997
Duska
1999
56 (20/36)
Morice
2001
Schilder
2002
22.2 (4/18)
3
1
0
0
71 (17/24)
26
5
0
0
Total
56.5
(68/109)
64
14
5
0
33.3 (2/6)
Fertility –Sparing Surgery in
Borderline Tumors of the Ovary:
•15% of all EOC
•Young age
•Early stage
•95% serous - mucinous
•Overall survival 95 %
Fertility Sparing Surgery
in Borderline Ovarian Tumors
•Staging
•Leaving the uterus
•Some functional ovarian tissue
in place
•Evaluation of endometrial
cavity?
Ovarian procedures in BOT
•BSO (very rare)
•USO
•Cystectomy
•Partial excision
•Cortical ovarian biopsy
for cryopreservation
After FSS
• Recurrence 7.7-31 %
Donnez, 2003
Morriu, 2001
Cutlieb, 1998
• Disease related death
0
• Pregnancy rates 31.8, 38.5
and 63.3 %
Donnez, 2003
Ovarian Tumors of Low
Malignant Potential
Study
Lim-Tam
1988
Gotlieb
1998
Morris 2000
Zanetta
2001
Morice 2001
Rao 2005
Boran 2005
No. Pts.
35
Stage
IA-III
No. Pregn.
8
39
IA-III
22 in 15
43
189
IA-III
IA-III
25 in 12
44 in 44
44
38
62
IA-III
IA-III
IA-III
17 in 14
6 in 5
10 in 10
FSS in MOGCTs
• 20-25 % of all ovarian
neoplasm
• Only 3 % of these are malignant
• Young age
• Early stage
• Generally unilateral
(Dysgerminoma 12%)
Fertility Sparing Surgery
Full staging
Removal of affected ovary
Preserving the contraleral ovary
Preserving of the uterus
+ Chemo
In early and selected advanced
stage
Survival in MOGCTs
The survival in
FSS is similar
to radical
surgery in
MOGCTs
Pregnancy after
surgery in MOGCTs
Number of patients
Pregnancy rate
29/32
76 %
19/20
95 % (Surg +Chemo)
16/20
80 % (Surg +Chemo)
12/12
100 % (Only surgery)
Low et al, Zanette et al Gerhenson et al
Obstetric Outcome in MOGCT
Author
% Pregnancy
Gershenson 100 (12/16)
1988
Term
Delivery
Abort.
Ektopic
Anomaly
22
8
16
26
38
0
--9
2
0
-----
0
0
0
3
0
11
0
3
Perrin
1999
------
Low
2000
95 (19/20)
Zanetta
2001
80 (16/20)
Tangir
2003
76 (25/33)
Toplam
87.75 110
(72/89)
Oncologic Outcome:
After Fertility Sparing Surgery:
EOC
MOGCTs BOT
Survival is
similiar to radical surgery
FSS in LMS
• 25% of uterine sarcomas
• 1% of all uterine
malignancies
• 0.29 of all myomectomies
(6815 myoma)
• 25% premenopausal
FSS in LMS
Local excision
(at least 0.5-1cm
tumor free border )
Endometrial Cancer
• Most frequent Gyn.Ca
• 25% premenopausal
• 5% under 40 age
• Type I good prognosis (PCOS)
• Grade I, EPR +
• Cure rate %95
Pretreatment Evaluation
• History (infertility...)
• Physicial Examination
• TVUSG
• D&C
• Abdominopelvic/ endovajinal
coil MRI
• Ca-125
Laparoscopic evaluation
or
Staging Laparotomy
Response to Progesterone
MRI Sensitivity %80 Specifity %100
Before and After Treatment
Progestogenic Agents
•
•
•
•
MPA 200-600 /mg/ day
Megace 40-160 /mg/day
IUD / Prog
Response Rate
Hyperplasia with Atypia
End. Ca
• Duration of Treatment
Range
3-6
Median
9
• Recurrens
Hyperplasia with Atypia
End. Ca
%83-94
%57-75.6
months
months
% 13
% 11-50
n
7
14
12
12
9
13
Response Rates to Progesterones in
Endometrial Cancer
Drug
Time
MA
3 ay
MA/ MPA
1 yıl
MA / MPA 3-18 ay
MPA
2-14 ay
MA / Tam
MA / MPA 3.5 ay
Regr.
4
9
9
9
8
13
67
*26
%55 IVF
Recur. Pregnancy
2
1
1
2
4
6
0
3
3
2
4
3
16
15
31
Kım 1997, Randal-Kurman 1997, Kaku 2001, Wang 2002, Gotlieb 2003
*Jadoul-Donnez 2003
Fertil Steril 2005;84; 1564
FSS in Endometrial
Cancer
• At young age
• Well differantiated End. Ca
• Stage IA, Grade I-II
• Progestin therapy
• Evaluation of end with 3 months
interval
• Fertility desire
FSS in Cervical Cancer
• %27.9 patients < 40 age (SEER)
• Cx Ca most prevalant in 35-39 years
of age
• Adenocarcinoma is a problem
• Squam/ Adeno (except
neuroendocrine type)
• IA-IB1*
*Tumor <2 cm, Deep Stromal Inv. <1 cm
FSS in Cervical Cancer
• Preinvazive
Ia1 LVSI (-)
• 1a1 LVSI (+)
• 1a2
• 1b1 2 cm Der:1 cm
Cone Only
Pelvic LND* +
Radikal
Trachelectomy**
• In selected cases with stage Ib-IIA ovarian
transposition,oocyte and/or embryo criopreservation
*Endoscopic/ Laparotomy / Sentinel Node
**Vaginal /Abdominal
In IA1 LVSI (-)
CONE
• Tumor free margin and post-cone
negative ECC
• Positive margin or positive ECC
RE-CONE
Clinical importance of
margin and ECC
Variables
Residual tumor
Margin
Negative
Positive
3%
22%
Margin and ECC
Negative
Positive
4%
33%
Pelvic Node Metastasis in
Stage IA1
Depth of
Invasion
1mm or less
1-3 mm
LNM +
0,1
0,5
Stage IA1 with LVSI (+)
IA2
Pelvic lymphadenectomy
Radical trachelectomy*
plus
Cervical cerclage
*Free margin >at least 5mm-1 cm
Why lymphadenectomy in
Stage IA2
Variables
LNM +
Invasive Rec
Death of Dis.
% LNM Metas.
7.3
3.1
2.3
Van Nagell et al..... Creasman et al
FSS in Stage IB1
•
•
•
•
Lesion ≤ 2cm
Depth of Inv ≤ 1cm
LNM negative
Upper cervical involvement (-)
Pelvic lymphadenectomy +
Radical trachelectomy
Radical trachelectomy
(1994 Dargent)
• Removal of primary
tumor
• Parametrectomy
• 1/3 upper vaginectomy
• Preserving uterine fundus
• Pelvic lymphadenectomy
Radical trachelectomy
•Abdominal
•Vaginal
•Lymphadenectomy
(Open and Endoscopic)
No difference between
Radical trachelectomy
and
Radical hysterectomy
for
Recurrence and Death
Pregnancy Results after VRT
n
Fertility
Desire
No.of Pregn/
Patient
Livebirth
96
72
93
30
19
10
42
42
39
13
4
4
56/33
48/31
22/18
14/8
4/3
4/4
34
28
18
9
2
2
315
144
148/97
93
Mathevet 2003, Plante 2004, Steed-Covens 2003, Shephard 2001,
Burnett 2003, Schlaerth 2003
Fertil Steril 2005;84:156
Reproductive Outcome after
Trachelectomy
• %25-43 infertility
Pre-operative (STD) ve post-operative (stenosis)
• Loss of fertility desire in %25
• Pregnancy rate %71
• Delivery rate % 41
• First trimester loss %21
• Second trimester loss %8
• Preterm delivery %20-%30
Cervical Insufficiency (Cerclage Saling Procedure, Ab,
USG ??)
PPROM
Informed Consent !!!!!
Boss et al, Gynecol Oncol, 2005
Conclusion-I
Fertility Preservation Options in
Females
•
•
•
•
Conservative surgery
Embryo cryopreservation
Oocyte cryopreservation
Ovarian tissue
cryopreservation
• Ovarian supression (GnRH
analogs)
Conclusion-II
Fertility Preservation Strategies
Treatment can be delayed
IVFEmbriyo
Freezing
Oocyte
freezing
Add TMX or Aromatase
Inhibitors for Est-sensitive
Treatment cannot
be delayed
Ovarian Tissue
Freezing
In vitro maturation in
high risk for ovarian
involvement
Thank you…