Download Fertility-Sparing Surgery in Gynaecological Oncology

Fertility Sparing
in
Gynecological Cancers
Fırat Ortaç, MD
Güven Hospital
Department of Obstetrics and
Gynecology
Cancer Treatment
Objective
Cure
Adverse Effects




Psychological effects
Cosmetic problems
Loss of organ function
Sexual and reproductive
dysfunction
Fertility sparing surgery
Goals of Fertility-Sparing
Surgery(FSS)
Preservation of reproductive
potential
Preservation of hormonal
function
Preservation of healthy body
image
No compromise in curability
FSS Objectives
Similiar oncologic outcomes
to standard therapy
Favorable obstetric outcome
Benefits > risks
Low morbidity
Defining prognostic factors
Evidence-based Data
Physician
Fertility Sparing Surgery
Fertility-Sparing
in
Gynecologic Oncology
 The patient and family must be:
aware of the problem
involved in the final decision
 Once the fertility has been
completed, demolitive procedure
should be considered
Fertility-Sparing
in
Gynecologic Oncology
Age
Desire to preserve fertility
Tumor factors
Histologic type, grade, others
Stage of disease
Principles in Treatment of EarlyStage Cervical Cancer
Patient’s general status
Desire of fertility
Tumor factors
Depth and width of invasion
Size of cervical lesion
LVSI
Traditional treatment of early stage
cervical cancer beyond
micro-invasion
Radical hysterectomy
+
PPLND
Loss of fertility
LVSI
Pelvik lenf nodu
metastazı
Pelvik rekürens
Lenfadenektomi – Radikal cerrahi
Spread of Cervical Cancer
Laterally (Dominant)  Parametrium
Vertically (rare)
Stage Ib and IIa  0%
Stage IIb  20%
Fertility Sparing Surgery
in
Early-Stage Cervical Cancer
ID<3 mm
LVSI(-)
CONIZATION
MARGIN (-)
FOLLOW-UP
Cold Conization
CONIZATION < 10 mm
Does not affect
fertility potential
Clin. Exp. Obstet. Gynecol, 1992: 19(1):40-2
Effect of Con on Pregnancy Outcome
< 15 mm
NO
EFFECT
Frencezy A, 1995
Haffenden DK, 1993
Tan L, 2004
< 18 mm
> 15 mm
> 18 mm
25% PRETERM LABOR
18% PROM
Sadler L. Et al., Am J Med Ass, 2004
Fertility Sparing Surgery in Early-Stage
Cervical Cancer
Stage Ia1 (LVS +)
Stage Ia2 (LVS )
Stage Ib-IIa (2cm)
Desire of fertility
Lymph Node Dissection
(L/S, L/T)
Node (+)
Node (-)
Sentinel Lymph Node
RVT
RAT
RT
Sentinel lymph node
Radical Trachelectomy
1994 Dargent
Vaginal Radical Trachelectomy (VRT)
in
Early-Stage Cervical Cancar
by Dargent in Lyon, France
Modification of the Schauta-Stoeckel
technique of vaginal radical hysterectomy
L/S
Pelvic
lymphadenectomy
Preservation of
the upper endocervix
and uterine corpus
Radical Trachelectomy(RT)
VRT-AbRT
Indications
 Patient who desires preservation of
fertility
 FIGO Stage Ia1 (+LVSI), Ia2, Ib1
 Lesions  2 cm in diameter
 Limited endocervical involvement
- MRI and colposcopy
Surgıcal procedure
 Lymph node dissection(Sentinel lymph node)
 Parametrectomy
 Trachelectomy (FS analyse- free margin 5-8 mm)
 Cervical circlage
RT
Feasibility
No evidence of lymph node metastasis
(Frozen section at L/S)(ultrastaging)
Upper endocervical margins free of
tumor (Frozen section)
VRT
Results
 Dargent (Lyon)
 Plante and Roy (Quebec)
 Covens (Toronto)
 Shepherd (London, UK)
 Total
82
44
58
40
224
VRT
Oncologic Outcome (N:24)
Follow-up (months)
Recurrences
 Parametrium
 Pelvic side wall
 Distant
30
7(3.1%)
3
1
3
No cervico-uterine recurrence
Pregnancy Results after VRT
n
Fertility
Desire
96
42
72
42
93
39
30
13
19
4
10
4
315
144
No.of Pregn/
Patient
56/33
48/31
22/18
14/8
4/3
4/4
148/97
Livebirth
34
28
18
9
2
2
93
Fertil Steril 2005;84:156
VRT
Conclusions
 Abdominal way is possible
 The risk of recurrence is unchanged
 Fertility is preserved
 But pregnancies are at high risk
 An international study is required to
confirm indications and limits of this
conservative technique
Preserving Fertility in Endometrial
Cancer
2% -14 % of endometrial
cancer
 40 years
Up to 25%
PCOS
G1
Early stage
Respond to
progestin
treatment
Preserving Fertility in Endometrial
Cancer
Stage Ia, G1
Standart treatment
TAH + BSO
Preserving Fertility in Endometrial
Cancer
Endometrial Cancer
Fertility Desire
Pretreatment Evaluation
Tumor
Grade
Depth
of MI
Tumor
Size
Hormone
receptor status
Favorable
prognosis
Flow cytometric
analysis
Preserving Fertility in Endometrial
Cancer
Inclusion Criteria



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
Age < 40 years
Nulliparous status
Endometrioid Carcinoma
G1
Presence of PgR
Normal serum levels of CA 125 (<35 u/mL) and CEA
(< 5 ng/mL)
 Tumor DNA index < 1.3
 Absence of MI or extrauterine spread (by vaginal USG
and MRI) ,surgıcal staging
Pretreatment Evaluation
History (infertility...)
Physicial Examination
TVUSG
D&C
Abdominopelvic/ endovajinal coil
MRI
Ca-125
Laparoscopic evaluation
or
Staging Laparotomy
Response to Progesterone
Preserving Fertility in Endometrial
Cancer
 Explain the patient the risk of conservative treatment
 Evaluate the patient for prognosis
 Medical treatment (Megestrol acetate 40-160 mg/d , MPA 30
mg/d  Tamoxifen 30 mg/d or GnRHa)
 Repeated D&C; hysteroscopy (+tubal blockage)
 No residual disease
 Assisted reproduction
 Elective hysterectomy when the patient no longer desires to
maintain fertility
Progestogenic Agents
MPA
Megace
IUD / Prog
Response Rate
Hyperplasia with Atypia
End. Ca
 Duration of Treatment
Range
Median
 Recurrens
Hyperplasia with Atypia
End. Ca




30/mg/ day
40-160 /mg/day
%83-94
%57-75.6
3-6 months
9 months
% 13
% 11-50
There is no consensus
Which progesterone formulation to use
What schedule to use
What dose to use
How long to treat
How often to resample
Preserving Fertility in Endometrial
Cancer
72 cases in literature
Positive response
histologically documented
55 cases (76%)
Endometrial Cancer
Literature Overview (1966-2006)
 No pts.= 53
 80% were nulliparous
 In 96% of them the tumor was well
differentiated
 At least 36 pregn. were obtained by ART
 70% of pts. Underwent a hysterectomy
after completing gestation
Uterine Leiomyosarcoma (LMS)
 Diagnosis
Pre-operative?
Intra-operative frozen section?
Histopathological evaluation of
hysterectomy or myomectomy
specimen.
Uterine LMS
Incidence
patients operated for
presumed leiomyoma
0.1-0.3%
Fertility Sparing Surgery
in
LMS
 Safe margin: 3-5 mm. ?
 <10 mitoses/per 10 HPF
 Solitary pedinculated mass
Fertility Sparing Surgery
in
LMS
Accurately restage the patients
Color doppler USG
Hysteroscopy
Chest X-ray
MRI or CT scan
Fertility Sparing Surgery
in
LMS
•Delivery
Cesarean section
Multiple uterine biopsies
should be taken.
Fertility Sparing Surgery
in
LMS
Lissoni A (Gynecol Oncol 70(3): 348-50 (1998)
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Between 1982-1996 (8 patients)
Median age: 29
All nulliparous
Tumor was confined to myoma
Mean mitotic count 6 per 10 HPF
3 pregnancies
Median follow-up 42 months
7 patients alive
One patient died (26 months after diagnosis).
Fertility Sparing
in
Epithelial Ovarian Cancer
and Borderline Tumors
Fertility Sparing Surgery in Epithelial
Ovarian Cancer and Borderline Tumors
Optimal Staging:
 USO or cystectomy (in BOT)
 Peritoneal washing and cytology
 Inspection of the contralateral ovarian
surface, biopsies of any suspicious lesions
Wedge resection of the opposite ovary?
 Staging biopsies of the peritoneal cavity
 Sampling of retroperitoneal lymph nodes or
radical lymphadenectomy since 1990
 Omentectomy, appendectomy.
Fertility Sparing Surgery
in
Borderline Tumors
 Recurrence rate in the patients
underwent conservative surgery
for border-line tumors is %7
Gynecol Oncol 55;552-6, 1994.
Border-line Tumors of the Ovary
Conservative Management and
Pregnancy Outcome
Cancer 1998 Jan, 1;82(1):141-6
 Retrospective review
 82 patients
 39 patients underwent conservative
management
 Three patients had a contralateral
recurrence (7%)
 22 pregnancies were achieved.
Invasive Epithelial Ovarian Cancer
and Border-Line Tumors
Desire for fertility
Endometrial biopsy
Optimal Staging
FROZEN
Stage Ia
G1 and Border-line
No further treatment
Stage Ia
G2, G3
Chemotherapy
Stage Ic-III
• Selected cases
• Requested by
patients herself
• Preliminary reports.
Can conservative surgical approach be used in
selected young patients with ovarian cancer who
would usually undergo radical operations.
Cancer 1998 Jan, 1;82(1):141-6
 Retrospective study between 1980-1994
 10 patients with high grade or limited
extraovarian disease
• Stage Ia G3
2
• Stage Ic
2
• Stage IIIa
2
• Stage IIIc
4
 All patients were given adjuvant CT
 All patients were alive median follow-up 70
months
 9 patients were menstruating regularly
 Three had became pregnant.
Ovarian Cancer Treatment
with Fertility-Sparing Therapy
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Stage IA and IC epithelial ovarian cancer
1965 to 2000, n=52
20 (%38) received chemotherapy
9 (17%) eventual TAH
5(10%) recurred, 2 died
24 (46%) attempted, 17 (33%) conceived
 26 term, 5 SAb
 33% take home baby
Schilder et al., Gynecol Oncol, 2002
Fertility Sparing Surgery in Epithelial
Ovarian Cancer and Borderline Tumors
CONCLUSIONS
 For more advanced stages, additional
investigation is needed.
 After completion of fertility, residual
ovary should be taken out.
 Incidence of ovarian cancer gets
higher with age.
 Screening method are unreliable.
Germ Cell Tumors of the Ovary
 Incidence: less than %5 of all
ovarian neoplasm.
 Age: the first and second decade
 Usually unilateral
FSS in Germ Cell Tumors of the Ovary
 1978 Forney first reported a case of
successful pregnancy in a 18 year-old with
EST of ovary.
Obstet Gynecol 52, 360-62 (1978)
 1985 Gershenson at the MD Anderson
Hospital.
48 patients with malignant germ cell
tumors
Full-term pregnancies in 6 cases
Cancer 56, 2756-2761 (1985)
FSS in Germ Cell Tumors of the Ovary
Rationales
 Unilaterality of tumor
 Improvement of prognosis by
modern combination chemotherapy
1970s the VAC regimen
1980s the PVB regimen
POMP/ACE.
Treatment of Malignant Ovarian Germ
Cell Tumors With Preservation of Fertility
A Report of 28 Cases / Cancer 42, 1152-1160 (1978)
 Tumor was confined to one ovary in all
cases.
 All patients were taken chemotherapy
except two with stage I immature
teratoma.
 More than 5 years survival in 13 cases
(59.1%)
 7 of 12 married patients, became pregnant,
all had term delivery.
Obstetric Outcome in GCT
Author
Gershenson
1988
Perrin
1999
Low
2000
Zanetta
2001
Tangir 2003
Toplam
% Pregnancy
Abort.
Ektopic
Anomaly
100 (12/16)
Term
Delivery
22
0
0
0
------
8
--
--
0
95 (19/20)
16
--
--
0
80 (16/20)
26
9
--
3
76 (25/33)
38
2
--
0
87.75
(72/89)
110
11
0
3
Fertility Sparing Surgery in Germ Cell
Tumors of the Ovary
Conclusion
Regardless of the stage is a safe
and practicable procedure in the
absence of involvement of
CONTRALATERAL OVARY
AND UTERUS
History of ART
 The new millenium:
2001 Clinic Specific Success
about 28% per cycle overall
Oocyte and ovarian slice
cryopreservation with function
(Oktay)
İnvitro maturation matures
Lancet,
March
13, 2004
Fertility Preservation Strategies
Treatment can be
delayed
IVF –embryo
freezing
Oocyte
freezing
Add tamoxifen or
aromatase inhibitors for
estrogen-sensitive
Treatment cannot
be delayed
Ovarian
tissue
freezing
In vitro maturation in high
risk for ovarian involvement
As we discover what
can be done, we need to
learn what should done
Thank you…
Fertility-Preserving
Treatment in Endometrial
Adenocarcinoma

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Stage IA, grade 1, 1991-9
N=9, average 32 years
Megace, tamoxifen, +GnRHa
8 CR, 1 TAH
4 pregnant
 2 term after ART, 2 ectopic
 %22 take home baby
Wang et al., Cancer, 2002