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 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
gynecological cancers
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
Risks
• Preservation
of fertility
• Maintanence
of endocrine
function
• 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 origins 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)
• Comprehensive 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
• 14% of EOC will occur under 40
years
• 25-30% of all EOC are early stage at
the diagnosis
• 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 6-12% in old
literature
• in the new literature,
this figures are about
2.5% in stage I disease
Gynecologic Oncology, 2008:110,345-353
Survival after FSS
5 yrs DFS
5 yrs OS
IA*
83
91
IC*
78
88
* rates are comparable for standart surgery
Gynecologic Oncology, 2008:110,345-353
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
31/17
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
Term
Delivery
Abort.
Ectopic
Anomaly
16
17
2
4
4
0
2
2
1
0
0
0
22.2 (4/18)
3
1
0
0
71 (17/24)
26
5
0
0
56.5
64
14
5
0
Colombo 100 (25/25)
1994
Zanetta
1997
Duska
1999
Morice
2001
Schilder
2002
Total
56 (20/36)
33.3 (2/6)
(68/109)
Fertility Sparing Surgery in
Borderline Tumors of the Ovary:
•15% of all EOC
•Young age
•Early stage
•95% serous–mucinous
•Overall survival 95%
Bilaterality: serous (25–50%), mucinous (5–10%), mixed (21%)
Ovarian procedures in BOT
•BSO (very rare)
•USO
•Cystectomy
•Partial excision
•Cortical ovarian biopsy
for cryopreservation
Recurrence Features in BOT
Procedure
Relapse (%)
• Adenexectomy
0–20
• Cystectomy
12–58
• Radical Surgery
3–6
• Invasive recurrence
2
• Invasive implant
20
EJSO 35, 643 – 648; 2009
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
• 5% of all ovarian neoplasm
• Young age
• Early stage
• Generally unilateral
(Dysgerminoma 12%)
• Highly lethal until BEP….
Fertility Sparing Surgery
Full staging
Removal of affected ovary
Preserving the contraleral ovary
Preserving of the uterus
+
Chemo
 In early and selected advanced stage
The survival in FSS
group is similar to
standard surgery in
MOGCTs
(equivalent cure with USO vs BSO±TAH)
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.
Ectopic
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)
Total
87.75 110
(72/89)
Endometrial Cancer
• Most frequent Gyn. Cancer
• 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/ endovaginal coil
MRI
• Ca-125
Laparoscopic evaluation
or
Staging Laparotomy
Response to
Progesterone
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
• Recurrence
Hyperplasia with Atypia
End. Ca
83-94%
57-75.6%
3-6 months
13%
11-50%
FSS in Endometrial Cancer
• At young age
• Well differantiated End. Ca
• Stage IA, Grade I-II
• Progestin therapy
• Evaluation of endometrium
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
• Preinvasive
Ia1, LVSI (-)
Cone Only
• 1a1, LVSI (+)
• 1a2
• 1b1, 2 cm, depth 1 cm
Pelvic LND* +
Radical
Trachelectomy**
in selected cases with stage Ib-IIA ovarian transposition,
oocyte and/or embryo criopreservation
* Endoscopic / Laparotomy / Sentinel Node
** Vaginal / Abdominal
IA1 LVSI (-)
CONE
• Tumor free margin and post-cone
negative ECC
• Positive margin or positive ECC
RE-CONE
Stage IA1 with LVSI (+)
IA2
Pelvic lymphadenectomy
Radical trachelectomy*
+
Cervical cerclage
*Free margin >at least 5mm-1 cm
Why lymphadenectomy in
Stage IA2 ?
Variables
LNM (+)
Invasive Rec
DOD
LNM Metas. (%)
7.3
3.1
2.3
Van Nagell et al, Creasman et al
Radical trachelectomy
(1994 Dargent)
• Removal of primary tumor
• Parametrectomy
• 1/3 upper vaginectomy
• Preserving uterine fundus
• Pelvic lymphadenectomy
Radical trachelectomy
• Abdominal
• Vaginal
• Lymphadenectomy
(Open or Endoscopic)
Obstetric Outcome in RVT
(pregnancies: 256)
TAB / EUP
1st trimester loss
2nd trimester loss
3rd trimester delivery
< 32 wks delivery
33–36.6 wks delivery
> 37 delivery
Gynecol Oncol. 2008; 111(S):105-110
Vaginal radical trachelectomy: An update.
Plante, M
#
14
47
22
158
18
26
102
%
5
18
8
62
12
16
65
Gynecol Oncol. 2010 May;117(2):350-7
Fertility-sparing options for early stage cervical
cancer.
Gien LT, Covens A
RVT, Oncologic Outcome
recurrence rate
mortality rate
4.2–5.3%
2.5–3.2%
Risk Factors for Recurrences
• tumor size ≥ 2cm
• LVSI [(12% (+) vs 2% (-)]
• unfavorable histology
Gynecol Oncol. 2010 May;117(2):350-7
Fertility-sparing options for early stage cervical cancer.
Gien LT, Covens A
Fertility Preservation
Options in Females
• Conservative surgery
• Embryo cryopreservation
• Oocyte cryopreservation
• Ovarian tissue cryopreservation
• Ovarian supression
(GnRH analogs)
Thank you for your attention