Fertility SparingFertility Sparing in in

Gynecological Cancers Gynecological Cancers

Fertility SparingFertility Sparing in in

Gynecological Cancers Gynecological Cancers

Melkeet singhMelkeet singh Department of ODepartment of O & & G G

Fertility SparingFertility Sparing Surgery Surgery in in Gynecological Cancers Gynecological Cancers Fertility SparingFertility Sparing Surgery Surgery in in Gynecological Cancers Gynecological Cancers

Most common gynaecological cancers in

reproductive age group includes

- Cervical Cancer - Endometrial Cancer - Ovarian Cancer

Incidence of Gynaecological cancer in Incidence of Gynaecological cancer in Reproductive age group.Reproductive age group.Incidence of Gynaecological cancer in Incidence of Gynaecological cancer in Reproductive age group.Reproductive age group.

Incidence for (age < 49 year) /100000

Cervical Cancer 1.5-14.9/100000

Endometrial cancer 1.2-24 /100000

Ovarian Cancer 1.6-16.6 /100000

Mean age of First Time Mean age of First Time MothersMothersMean age of First Time Mean age of First Time MothersMothersAge 30-34 → 28.4%Age 35-39 → 10.4%Age 40-44 → 2%

40% of first time births occurs beyond age of 30. Among the reproductive age group, those beyond age of 30

are at greater risk of malignancy - which can jeopardize fertility.

Need for fertility Sparing Surgery.

Cancer TreatmentCancer Treatment

ObjectiveObjective

CureCure

Adverse EffectsAdverse Effects Psychological effectsPsychological effects Cosmetic problemsCosmetic problems Loss of organ functionLoss of organ function Sexual and reproductive Sexual and reproductive

dysfunctiondysfunction

Fertility Fertility ImpairedImpaired

GoalsGoals / Objectives / Objectives of of FSS FSSGoalsGoals / Objectives / Objectives of of FSS FSS

Preservation of reproductive potential Preservation of hormonal function Similiar outcomes to standard therapy Favorable obstetric outcome Benefits > risk

FSSFSS - - CounselingCounselingFSSFSS - - CounselingCounseling

Patient & family aware of the problem.Patient & family aware of the problem.

Aware that they are assuming an undefined risk.Aware that they are assuming an undefined risk.

Aware of limited data on the options.Aware of limited data on the options.

Options are not standard Therapeutic approaches.Options are not standard Therapeutic approaches.

Patient must be extremely compliant with follow up.Patient must be extremely compliant with follow up.

Once fertility Once fertility completed, definitive procedure consideredcompleted, definitive procedure considered

FSSFSS – – PrerequisitesPrerequisitesFSSFSS – – PrerequisitesPrerequisites

Realistic probabilities of achieving conception based on Realistic probabilities of achieving conception based on age, history and infertility evaluationage, history and infertility evaluation

Desire to preserve Desire to preserve fertilityfertility

Tumor factors-Tumor factors-hhistologic type, grade.istologic type, grade.

Availability of ARTAvailability of ART

Abnormal smear → Colposcopy + Biopsy → Cone Biopsy

•No lesion

CIN Microscopic CaCx

Horizontal ≤7mm + Invasion < 3 mm

1A1

1A1- LN mets 0.5% Recurrence 2% LVSI 8-29%

LVSI - LVSI +

TAHBSOIntracavitary RT

Fertility desiredCONE Enough.

≤ 7mm + Invasion 3-5 mm

1A2

1A2 LN mets 6-14% Recurrence 4% LVSI 53%

Modified RH +PLND

Fertility desiredCONE + PLNDTrachelectomy + PLND

•RT

>7mm > 5 mm

1B1-11A

RH + PLND

In selected cases if fertility desired - Trachelectomy + PLND

Nodes positive → Radiotherapy

•Stage 1A1 – Squamous CarcinomaStage 1A1 – Squamous Carcinoma

•A loop cone excision of the cervix is sufficient treatment

.

AdenocarcinomaAdenocarcinoma

•Skip lesions can occur

? Just Pre-invasive

Cone – Fertility & Pregnancy Outcome

< 15 mm

NO EFFECT

> 15 mm

25% PRETERM LABOR 18% PROM

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

Frencezy A, 1995Haffenden DK, 1993Tan L, 2004

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

TrachelectomyTrachelectomyTrachelectomyTrachelectomy

Abdominal / Vaginal

Nodes must be assessed prior to procedure via frozen section

Includes resection of the cervix + upper 2-cm of vagina + parametrium, with preservation of the uterine corpus.

The uterine corpus is then sutured to the upper vagina.

Cervical Circulage

Trachelectomy - CriteriaTrachelectomy - CriteriaTrachelectomy - CriteriaTrachelectomy - Criteria A desire for fertility. No documentation of infertility. A proven diagnosis of cervical cancer Stage IA2 disease to stage IB1 disease Tumor limited to cervix. Tumor less than 2 cm No evidence of nodal metastases. Limited endo cervical involvement - Upper endocervical Limited endo cervical involvement - Upper endocervical

margins free of tumour (Frozen section) margins free of tumour (Frozen section) && MRIMRI

Trachelectomy Trachelectomy -Results-ResultsTrachelectomy Trachelectomy -Results-ResultsMeta-analysisMeta-analysis

Dargent (Lyon)Dargent (Lyon) 8282 Plante and Roy (Quebec)Plante and Roy (Quebec) 4444 Covens (Toronto) Covens (Toronto) 5858 Shepherd (London, UK) Shepherd (London, UK) 4040 TotalTotal 224224

RecurrencesRecurrences 9(5.8%)9(5.8%) Recurrences in Radical hysterectomy 4.4%Recurrences in Radical hysterectomy 4.4% 5 years survival in both group 97%5 years survival in both group 97%

Pregnancy OutcomePregnancy OutcomeProcedure 315Procedure 315Documented 114 pregnancies in 97 patients Documented 114 pregnancies in 97 patients Live births 93Live births 93

Fertil Steril 2005;84:156

Preserving Fertility in Endometrial Preserving Fertility in Endometrial Cancer Cancer

Preserving Fertility in Endometrial Preserving Fertility in Endometrial Cancer Cancer

2% -14 % of endometrial 2% -14 % of endometrial cancercancer

40 years40 years

Up to 25% Up to 25% PCOSPCOS

GG11 Early stageEarly stage

Respond to Respond to progestin progestin treatment treatment

Early Early StageStage Ca Endo ( Ca Endo (Ia, Ia, G1)G1)

StandarStandardd treatment treatment

TAH + BSOTAH + BSO +/- +/- PLNDPLND

Preserving Fertility in Endometrial Preserving Fertility in Endometrial CancerCancer

Preserving Fertility in Endometrial Preserving Fertility in Endometrial CancerCancer

Is there a fertility sparing surgery for cancer endometrium ?.Is there a fertility sparing surgery for cancer endometrium ?.

FSS in Endometrial CancerFSS in Endometrial CancerFSS in Endometrial CancerFSS in Endometrial Cancer

I. Mazzon, et al (2010) described a three-step Technique , each characterized by a pathologic analysis.

(1) removal of the tumor, (2) removal of endometrium adjacent to tumor (3) removal of the myometrium underlying the tumor.

Followed by megestrol acetate 160 mg/day x 6 /12

Biopsies at 3, 6, 9, and 12 months were negative

4/6 (66%) achieved childbearing.

I. Mazzon, G. Corrado, V. Masciullo, D. Morricone, G. Ferrandina, and G.Scambia “Conservative surgical management of stage IA endometrial carcinoma for fertility preservation,” Fertility and Sterility, vol. 93, no. 4, pp. 1286–1289, 2010.

Patient and family aware of the possible risk

Nulliparous Status.

History (infertility )

Histology type- Endometroid type. Clear cell and UPSC excluded .

Grade 1 malignancy.

Tumour size

Myometrial invasion excluded.

ART facilities available

After single delivery –hysterectomy

Conservative ManagementConservative Management Endometrial Cancer Endometrial Cancer CriteriaCriteria

Conservative ManagementConservative Management Endometrial Cancer Endometrial Cancer CriteriaCriteria

Complex Atypical Complex Atypical HyperplasiaHyperplasiaComplex Atypical Complex Atypical HyperplasiaHyperplasia

Precursor to cancer.

Commonly detected in patients with PCOS.

30-60 % of hysterectomy performed for CAH are found to have frank malignancy.

Standard recommendations is hysterectomy.

Fertility preservation -hormonal therapy is an option after formal D&C

Hormonal therapy Hormonal therapy Hormonal therapy Hormonal therapy

Hormonal Therapy Endometrial Hyperplasia Endometrial Cancer

With out Atypia With Atypia

Medroxyprogestrone Acetate

10-30 mg PO

100 mg PO 400-800 mg in divided

dose daily

Megestrol Acetate 40 mg PO

160 mg PO 160 mg PO

Depo-ProveraMirena coil

Various dosages used in trials

No consensus on type, dosage, duration, frequency, route and maintainance therapy

Endometrial CancerEndometrial CancerEndometrial CancerEndometrial Cancer

Literature Overview (1961-2003)

Patients = 81

62 (76%) responded

Median time to response 12/52 (range 4-60/52)

15(24%) recurrence

7 retreated with hormones -5 responded.

20 patients conceived - 12 by ART

31 life births. ( some conceived more than once)

Ramirez PT, Frumovitz M, Bodurka DC et al. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol 2004;95:133–138.

Standart treatmentStandart treatment

TAH BSOTAH BSO + Omentec + append + PLND + PAND + washings + peritoneal biopsies + Omentec + append + PLND + PAND + washings + peritoneal biopsies

Preserving Fertility in Preserving Fertility in Epithelial OvarianEpithelial Ovarian Cancer CancerPreserving Fertility in Preserving Fertility in Epithelial OvarianEpithelial Ovarian Cancer Cancer

Fertility Sparing SurgeryFertility Sparing Surgery

Preserve Uterus and contra-lateral OvaryPreserve Uterus and contra-lateral Ovary

118 early ovarian cancers that appeared to have disease limited to one ovary were however subjected to full staging. 3/118 (2.5%) of contra-lateral ovary were found to have microscopic disease. This risk must be conveyed to patients concerned. ( Bejamin et al)

FSS-Epithelial Ovarian CancerFSS-Epithelial Ovarian CancerFSS-Epithelial Ovarian CancerFSS-Epithelial Ovarian Cancer

Histology type Endometroid, Mucinous, Serous (Clear cell excluded)

Stage 1A

Grade 1 and possibly 2.

After completion of fertility residual ovary and uterus should be taken out

Stage IA G1Stage IA G1

No further treatment

Stage IAStage IAG2, G3G2, G3

Chemotherapy

Stage IC-IIIStage IC-IIISelected casesrequested by patients

HistologyHistology

Invasive Epithelial Ovarian CancerInvasive Epithelial Ovarian Cancer

Modified Staging

Chemotherapy

Chemotherapy and FertilityChemotherapy and FertilityChemotherapy and FertilityChemotherapy and Fertility

Premature ovarian failure after chemotherapy is more common with alkylating agents cyclophosphamide ( upto 68%)

Ovarian failure less common with taxol and carboplatin (15-25%)

Epithelial Epithelial Ovarian Cancer Treatment with Ovarian Cancer Treatment with Fertility-Sparing Therapy Fertility-Sparing Therapy Epithelial Epithelial Ovarian Cancer Treatment with Ovarian Cancer Treatment with Fertility-Sparing Therapy Fertility-Sparing Therapy

Stage IA and IC epithelial ovarian cancerStage IA and IC epithelial ovarian cancer 1965 to 2000, n=521965 to 2000, n=52 20 (%38) received chemotherapy20 (%38) received chemotherapy 9 (17%) eventual TAH9 (17%) eventual TAH 5(10%) recurred, 2 died5(10%) recurred, 2 died 24 (46%) attempted, 17 (33%) conceived 24 (46%) attempted, 17 (33%) conceived

26 ter26 termm

Schilder et al., Gynecol Oncol, 2002Schilder et al., Gynecol Oncol, 2002

Germ Cell TumorGerm Cell Tumorss of the Ovary of the OvaryGerm Cell TumorGerm Cell Tumorss of the Ovary of the Ovary

Age - first and second decadeAge - first and second decade

Usually unilateralUsually unilateral

Highly chemo sensitive to BEPHighly chemo sensitive to BEP

Even advance stage responds wellEven advance stage responds well

Fertility preserving surgery is the normFertility preserving surgery is the norm

A Report of 28 germ cell / Cancer 42, 1152-1160 A Report of 28 germ cell / Cancer 42, 1152-1160 - 26 received chemotherapy except two with stage I immature teratoma.- 26 received chemotherapy except two with stage I immature teratoma.- 7 of 12 married patients, became pregnant, all had term delivery.- 7 of 12 married patients, became pregnant, all had term delivery.

Borderline ovarian tumourBorderline ovarian tumourBorderline ovarian tumourBorderline ovarian tumour

Oophorectomy is not necessary if the initial operation was a cystectomy

Surgical staging is not indicated

Risk of recurrence- 6% for ipsilateral ovary ,3% for contralateral ovary and 3% for bilateral recurrence

5 Years survival 95-97%

Recurrence higher in those with fertility sparing surgery but survival is similar to those who had a TAHBSO.

Retrospective reviewRetrospective review 82 patients82 patients 39 patients conservative management39 patients conservative management Three patients contralateral recurrence (7%)Three patients contralateral recurrence (7%) 22 pregnancies were achieved.22 pregnancies were achieved.

Border-line Tumors of the Ovary Border-line Tumors of the Ovary Conservative Management and Conservative Management and

Pregnancy OutcomePregnancy Outcome

Border-line Tumors of the Ovary Border-line Tumors of the Ovary Conservative Management and Conservative Management and

Pregnancy OutcomePregnancy OutcomeCancer 1998 Jan, 1;82(1):141-6Cancer 1998 Jan, 1;82(1):141-6

Thank you…Thank you…Thank you…Thank you…

Cancer TreatmentCancer Treatment

ObjectiveObjective

CureCure

Adverse EffectsAdverse Effects Psychological effectsPsychological effects Cosmetic problemsCosmetic problems Loss of organ functionLoss of organ function Sexual and reproductive Sexual and reproductive

dysfunctiondysfunction

Fertility Fertility ImpairedImpaired