Fertility Sparing in Gynecological Cancers

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Fertility Sparing in Gynecological Cancers

• Firat Ortaç, MD
• Güven Hospital
• Department of Obstetrics and Gynecology

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• Cancer Treatment

Objective

• Adverse Effects
• Psychological effects
• Cosmetic problems
• Loss of organ function
• Sexual and reproductive dysfunction

Cure
Fertility sparing surgery
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Goals of Fertility-Sparing Surgery(FSS)

• Preservation of reproductive potential
• Preservation of hormonal function
• Preservation of healthy body image
• No compromise in curability

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FSS Objectives

• Similiar oncologic outcomes to standard therapy
• Favorable obstetric outcome
• Benefits gt risks
• Low morbidity

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• Defining prognostic factors
• Evidence-based Data

Physician
Fertility Sparing Surgery
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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

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Fertility-Sparing in Gynecologic Oncology

• Age
• Desire to preserve fertility
• Tumor factors
• Histologic type, grade, others
• Stage of disease

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Principles in Treatment of Early-Stage Cervical
Cancer

• Patients general status
• Desire of fertility
• Tumor factors
• Depth and width of invasion
• Size of cervical lesion
• LVSI

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Traditional treatment of early stage cervical
cancer beyond micro-invasion
Radical hysterectomy PPLND
Loss of fertility
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LVSI
Pelvik lenf nodu metastazi
Pelvik rekürens
Lenfadenektomi Radikal cerrahi
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Spread of Cervical Cancer

• Laterally (Dominant) ? Parametrium
• Vertically (rare)
• Stage Ib and IIa ? 0
• Stage IIb ? 20

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Fertility Sparing Surgery in Early-Stage
Cervical Cancer
IDlt3 mm LVSI(-)
CONIZATION
MARGIN (-)
FOLLOW-UP
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Cold Conization
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CONIZATION lt 10 mm

• Does not affect fertility potential

Clin. Exp. Obstet. Gynecol, 1992 19(1)40-2
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Effect of Con on Pregnancy Outcome
lt 15 mm NO EFFECT
Frencezy A, 1995 Haffenden DK, 1993 Tan L, 2004
lt 18 mm
gt 15 mm
25 PRETERM LABOR 18 PROM
Sadler L. Et al., Am J Med Ass, 2004
gt 18 mm
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Fertility Sparing Surgery in Early-Stage Cervical
CancerStage Ia1 (LVS )Stage Ia2 (LVS ?)Stage
Ib-IIa (?2cm)
Desire of fertility
Lymph Node Dissection (L/S, L/T)
Node ()
Node (-)
Sentinel Lymph Node
RT
RAT
RVT
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Sentinel lymph node
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Radical Trachelectomy
1994 ?Dargent
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Vaginal Radical Trachelectomy (VRT)inEarly-Stage
Cervical Cancar

• by Dargent in Lyon, France
• Modification of the Schauta-Stoeckel technique of
  vaginal radical hysterectomy

Preservation of the upper endocervix and uterine
corpus
L/S Pelvic lymphadenectomy
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Radical Trachelectomy(RT)
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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

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Surgical procedure

• Lymph node dissection(Sentinel lymph node)
• Parametrectomy
• Trachelectomy (FS analyse- free margin 5-8 mm)
• Cervical circlage

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RT

• Feasibility
• No evidence of lymph node metastasis (Frozen
  section at L/S)(ultrastaging)
• Upper endocervical margins free of tumor (Frozen
  section)

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VRT

• Results
• Dargent (Lyon) 82
• Plante and Roy (Quebec) 44
• Covens (Toronto) 58
• Shepherd (London, UK) 40
• Total 224

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VRT

• Oncologic Outcome (N24)
• Follow-up (months) 30
• Recurrences 7(3.1)
• Parametrium 3
• Pelvic side wall 1
• Distant 3
• No cervico-uterine recurrence

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Pregnancy Results after VRT
n Fertility Desire No.of Pregn/ Patient Livebirth
96 42 56/33 34
72 42 48/31 28
93 39 22/18 18
30 13 14/8 9
19 4 4/3 2
10 4 4/4 2
315 144 148/97 93

Fertil Steril 200584156
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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

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Preserving Fertility in Endometrial Cancer

• 2 -14 of endometrial cancer

? 40 years
Up to 25 PCOS
G1 Early stage
Respond to progestin treatment
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Preserving Fertility in Endometrial Cancer

• Stage Ia, G1

Standart treatment
TAH BSO
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Preserving Fertility in Endometrial Cancer

• Endometrial Cancer

Fertility Desire
Pretreatment Evaluation
Tumor Grade
Depth of MI
Tumor Size
Hormone receptor status
Flow cytometric analysis
Favorable prognosis
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Preserving Fertility in Endometrial Cancer

• Inclusion Criteria
• Age lt 40 years
• Nulliparous status
• Endometrioid Carcinoma
• G1
• Presence of PgR
• Normal serum levels of CA 125 (lt35 u/mL) and CEA
  (lt 5 ng/mL)
• Tumor DNA index lt 1.3
• Absence of MI or extrauterine spread (by vaginal
  USG and MRI) ,surgical staging

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Pretreatment Evaluation

• History (infertility...)
• Physicial Examination
• TVUSG
• DC
• Abdominopelvic/ endovajinal coil MRI
• Ca-125

Laparoscopic evaluation
Response to Progesterone
or
Staging Laparotomy
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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 DC hysteroscopy (tubal blockage)
• No residual disease
• Assisted reproduction
• Elective hysterectomy when the patient no longer
  desires to maintain fertility

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Progestogenic Agents

• MPA 30/mg/ day
• Megace 40-160 /mg/day
• IUD / Prog
• Response Rate
• Hyperplasia with Atypia 83-94
• End. Ca
  57-75.6
• Duration of Treatment
• Range 3-6
  months
• Median 9
  months
• Recurrens
• Hyperplasia with Atypia 13
• End. Ca
  11-50

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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

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Preserving Fertility in Endometrial Cancer

• 72 cases in literature

Positive response histologically documented 55
cases (76)
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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

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Uterine Leiomyosarcoma (LMS)

• Diagnosis
• Pre-operative?
• Intra-operative frozen section?
• Histopathological evaluation of hysterectomy or
  myomectomy specimen.

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Uterine LMS

• Incidence

patients operated for presumed leiomyoma
0.1-0.3
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Fertility Sparing Surgery in LMS

• Safe margin 3-5 mm. ?
• lt10 mitoses/per 10 HPF
• Solitary pedinculated mass

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Fertility Sparing Surgery in LMS

• Accurately restage the patients
• Color doppler USG
• Hysteroscopy
• Chest X-ray
• MRI or CT scan

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Fertility Sparing Surgery in LMS

• Delivery

• Cesarean section
• Multiple uterine biopsies should be taken.

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Fertility Sparing Surgery in LMS
Lissoni A (Gynecol Oncol 70(3) 348-50 (1998)

• 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).

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Fertility Sparing in Epithelial Ovarian Cancer
and Borderline Tumors
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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.

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Fertility Sparing Surgery in Borderline Tumors

• Recurrence rate in the patients underwent
  conservative surgery for border-line tumors is 7

Gynecol Oncol 55552-6, 1994.
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Border-line Tumors of the Ovary Conservative
Management and Pregnancy Outcome
Cancer 1998 Jan, 182(1)141-6

• Retrospective review
• 82 patients
• 39 patients underwent conservative management
• Three patients had a contralateral recurrence
  (7)
• 22 pregnancies were achieved.

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Invasive Epithelial Ovarian Cancer and
Border-Line Tumors
Desire for fertility
Endometrial biopsy
Optimal Staging
FROZEN

• Stage Ic-III
• Selected cases
• Requested by patients herself
• Preliminary reports.

Stage Ia G1 and Border-line
Stage Ia G2, G3
No further treatment
Chemotherapy
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• Can conservative surgical approach be used in
  selected young patients with ovarian cancer who
  would usually undergo radical operations.
• Cancer 1998 Jan, 182(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.

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Ovarian Cancer Treatment with Fertility-Sparing
Therapy

• Stage IA and IC epithelial ovarian cancer
• 1965 to 2000, n52
• 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
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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.

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Germ Cell Tumors of the Ovary

• Incidence less than 5 of all ovarian neoplasm.
• Age the first and second decade
• Usually unilateral

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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)

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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.

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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.

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Obstetric
Outcome in GCT
Author Pregnancy Term Delivery Abort. Ektopic Anomaly
Gershenson 1988 100 (12/16) 22 0 0 0
Perrin 1999 ------ 8 -- -- 0
Low 2000 95 (19/20) 16 -- -- 0
Zanetta 2001 80 (16/20) 26 9 -- 3
Tangir 2003 76 (25/33) 38 2 -- 0
Toplam 87.75 (72/89) 110 11 0 3
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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

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History of ART

• The new millenium
• 2001 Clinic Specific Success about 28 per cycle
  overall
• Oocyte and ovarian slice cryopreservation with
  function (Oktay)
• Invitro maturation matures

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Lancet, March 13, 2004
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Fertility Preservation Strategies
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As we discover what can be done, we need to learn
what should done
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Thank you
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Fertility-Preserving Treatment in Endometrial
Adenocarcinoma

• Stage IA, grade 1, 1991-9
• N9, 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