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Fertility Sparing in Gynecological Cancers . Fırat Ortaç, MD Güven Hospital Department of Obstetrics and Gynecology . Cancer Treatment. Objective. Adverse Effects Psychological effects Cosmetic problems Loss of organ function Sexual and reproductive dysfunction. Cure.

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fertility sparing in gynecological cancers
Fertility Sparing in Gynecological Cancers

Fırat Ortaç, MD

Güven Hospital

Department of Obstetrics and Gynecology

slide2
Cancer Treatment

Objective

Adverse Effects

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

Cure

Fertility sparing surgery

goals of fertility sparing surgery fss
Goals of Fertility-SparingSurgery(FSS)

Preservation of reproductive potential

Preservation of hormonal function

Preservation of healthy body image

No compromise in curability

fss objectives
FSS Objectives
  • Similiar oncologic outcomes to standard therapy
  • Favorable obstetric outcome
  • Benefits > risks
  • Low morbidity
slide5
Defining prognostic factors

Evidence-based Data

Physician

Fertility Sparing Surgery

fertility sparing in gynecologic oncology
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 gyn e cologic oncology
Fertility-Sparing in Gynecologic Oncology
  • Age
  • Desire to preserve fertility
  • Tumor factors

Histologic type, grade, others

  • Stage of disease
principles in treatment of early stage cervical cancer
Principles in Treatment of Early-Stage Cervical Cancer
  • Patient’s general status
  • Desire of fertility
  • Tumor factors
    • Depth and width of invasion
    • Size of cervical lesion
    • LVSI
slide9

Traditional treatment of early stage

cervical cancer beyond

micro-invasion

Radical hysterectomy

+

PPLND

Loss of fertility

slide10

LVSI

Pelvik lenf nodu metastazı

Pelvik rekürens

Lenfadenektomi – Radikal cerrahi

spread of cervical cancer
Spread of Cervical Cancer
  • Laterally (Dominant)  Parametrium
  • Vertically (rare)
    • Stage Ib and IIa  0%
    • Stage IIb  20%
f ertility sparing surgery in early stage cervical cancer
Fertility Sparing Surgery inEarly-Stage Cervical Cancer

ID<3 mm

LVSI(-)

CONIZATION

MARGIN (-)

FOLLOW-UP

conization 10 mm
CONIZATION < 10 mm

Does not affect fertility potential

Clin. Exp.Obstet. Gynecol, 1992: 19(1):40-2

slide15

Effect of Con on Pregnancy Outcome

< 15 mm NO EFFECT

Frencezy A, 1995

Haffenden DK, 1993

Tan L, 2004

< 18 mm

> 15 mm

25% PRETERM LABOR

18% PROM

Sadler L. Et al., Am J Med Ass, 2004

> 18 mm

slide16
Fertility Sparing SurgeryinEarly-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

radical trachelectomy
Radical Trachelectomy

1994 Dargent

vaginal radical trachelectomy vrt in early stage cervical cancar
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

vr t abrt
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

slide22

Surgıcal procedure

  • Lymph node dissection(Sentinel lymph node)
  • Parametrectomy
  • Trachelectomy (FS analyse- free margin 5-8 mm)
  • Cervical circlage
slide23
RT

Feasibility

  • No evidence of lymph node metastasis (Frozen section at L/S)(ultrastaging)
  • Upper endocervical margins free of tumor (Frozen section)
slide24
VRT

Results

  • Dargent (Lyon) 82
  • Plante and Roy (Quebec) 44
  • Covens (Toronto) 58
  • Shepherd (London, UK) 40
  • Total 224
slide25
VRT

Oncologic Outcome (N:24)

Follow-up (months) 30

Recurrences 7(3.1%)

  • Parametrium 3
  • Pelvic side wall1
  • Distant 3

No cervico-uterine recurrence

pregnancy results after vrt
Pregnancy Results after VRT

Fertil Steril 2005;84:156

slide27
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
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 cancer29
Preserving Fertility in Endometrial Cancer

Stage Ia, G1

Standart treatment

TAH + BSO

preserving fertility in endometrial cancer30
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

preserving fertility in endometrial cancer31
Preserving Fertility in Endometrial Cancer

Inclusion Criteria

  • 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
Pretreatment Evaluation

History (infertility...)

Physicial Examination

TVUSG

D&C

Abdominopelvic/ endovajinal coil MRI

Ca-125

Laparoscopic evaluation

Response to Progesterone

or

Staging Laparotomy

preserving fertility in endometrial cancer33
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
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

there is no consensus
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 cancer36
Preserving Fertility in Endometrial Cancer

72 cases in literature

Positive response

histologically documented

55 cases (76%)

endometrial cancer
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
Uterine Leiomyosarcoma (LMS)
  • Diagnosis
    • Pre-operative?
    • Intra-operative frozen section?
    • Histopathological evaluation ofhysterectomy or myomectomyspecimen.
uterine l ms
Uterine LMS

Incidence

patients operated for presumed leiomyoma

0.1-0.3%

f ertility sparing surgery in lms
Fertility Sparing Surgery inLMS
  • Safe margin: 3-5 mm. ?
  • <10 mitoses/per 10 HPF
  • Solitary pedinculated mass
f ertility sparing surgery in lms41
Fertility Sparing Surgery inLMS

Accurately restage the patients

  • Color doppler USG
  • Hysteroscopy
  • Chest X-ray
  • MRI or CT scan
f ertility sparing surgery in lms42
Fertility Sparing SurgeryinLMS

Cesarean section

Multiple uterine biopsies should be taken.

Delivery

f ertility sparing surgery in lms43
Fertility Sparing SurgeryinLMS
  • 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).

Lissoni A (Gynecol Oncol 70(3): 348-50 (1998)

f ertility sparing surgery in epithelial ovarian cancer and borderline tumors
Fertility Sparing Surgeryin 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.
f ertility sparing surgery in borderline tumors
Fertility Sparing Surgeryin 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
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.
slide48

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

slide49
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
Ovarian Cancer Treatment with Fertility-Sparing Therapy
  • 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

f ertility sparing surgery in epithelial ovarian cancer and borderline tumors51
Fertility Sparing Surgeryin 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 tumor s of the ovary
Germ Cell Tumors of the Ovary
  • Incidence: less than %5 of all ovarian neoplasm.
  • Age: the first and second decade
  • Usually unilateral
f ss in germ cell tumors of the ovary
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)

f ss in germ cell tumors of the ovary54
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
Treatment of Malignant Ovarian Germ Cell Tumors With Preservation of Fertility
  • 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.

A Report of 28 Cases / Cancer 42, 1152-1160 (1978)

f ertility sparing surgery in germ cell tumors of the ovary
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
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
fertility preserving treatment in endometrial adenocarcinoma
Fertility-Preserving Treatment in Endometrial Adenocarcinoma
  • 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