Fertility Preservation for Gynecologic Cancer Patients

Shaukat Khanum Memorial Cancer Hospital and Research Centre
Iqra Yasin
Fertility Preservation for
Gynecologic Cancer Patients
Fellow Gynecologic Oncology
SKMCH & RC, Lahore

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Outline
 Introduction
 Cervical Cancer
 Endometrial Cancer
 Ovarian Cancer
 Conclusion
 References

Introduction
 Overall cancer risk in females <39 years (1:39)
 In young women
 Cervical cancer 2%
 Endometrial cancer 5%
 Ovarian cancer 12 %
 5 year survival
 46% in ovarian cancer to 80% in endometrial cancer
 Over 90% in borderline ovarian tumor

Introduction
 Gynecologic Malignancies – Often diagnosed in postmenopausal
age
 Rise in a trend seen in premenopausal age
 Traditional management = TAH + BSO (permanent sterility)
 Fertility preservation: important at young age
 Patient selection: Crucial

Cervical Cancer
 Incidence: 1.5 – 14.9 per 100,000 (20 – 49 years)
 45 % of early-stage IB surgically removed:
 < 40 years of age.
 Standard management:
 Radical hysterectomy + systematic pelvic LND
 Ovarian preservation and upper transposition:
 Pelvic RT in young age

Cervical Cancer
 Fertility sparing procedures
1. Excisional conization of the cervix

Cervical Cancer
 Indications of cervical conization (microscopic disease)
Stage DOI Horizontal
Spread
Cervical
Conization
Risk of LN
metastases
Systemic
Pelvic LND
IA1 < 3 mm < 7 mm + 0.5 – 1.5 % -
IA2 < 5 mm < 7 mm + 5 – 8 % +

Cervical Cancer
2. Radical Trachelectomy/cervicectomy (Greek: trachelos – neck)
Approaches
a. Vaginal
b. Abdominal
a. Pediatric, nullipara
b. distorted anatomy
c. Cervical stump tumor
d. Exophytic cervical tumor

Cervical Cancer
2. Radical Trachelectomy (Patient Selection)
1. Strong desire to preserve fertility
2. Histopathological diagnosis with proven diagnosis of cervical cancer by
expertise
3. SCC / AdenoCA / Adenosquamous CA
4. Stage IA1 with LVSI , IA2 and IB1
5. Tumor size < 2 cm
6. No evidence of pelvic LN or distant metastases

Cervical Cancer
2. Radical Trachelectomy (Preoperative assessment)
1. Colposcopy
2. Histopathology review by second expertise (type, depth, LVSI)
3. MRI

Cervical Cancer
2. Radical Trachelectomy (steps)
a) Systemic Pelvic Lymphadenectomy
b) Excision of cervix + Para cervix + 1-2 cm of vagina
c) Upper cervical or isthmic cerclage
d) Reconstruction of uterine corpus to upper vagina

Cervical Cancer

Cervical Cancer
 Radical Trachelectomy (Follow-up)
 Cytologic (vaginal +isthmic smear) and colposcopic
evaluation
 0-2 years ( every 3-4 months) , > 2 years (every 6 months)
 Yearly MRI

Cervical Cancer
 Radical Trachelectomy
 Obstetrical Outcomes
 2nd trimester miscarriage
 Preterm birth
 Oncologic Outcomes
 5 years survival 98.4 %
 Relapse rate 4.5 %

Cervical Cancer
 Radical vaginal Trachelectomy vs radical hysterectomy
 Same or less morbidity
 No significant difference in intra and post operative
complications
 No difference in 5-year OS, RFS, PFS

Cervical Cancer
 Radical Trachelectomy (Conclusion)
Radical hysterectomy, the “gold standard” traditional treatment
for patients with early stage cervical cancer has been recently
replaced by radical trachelectomy – vaginal or abdominal route
– for young women with strong desire for fertility preservation.

Cervical Cancer (NCCN / Summary)

Endometrial Cancer
 Most common gynecologic malignancy
 Median age of diagnosis: 61 years
 Incidence: 1.2 – 24 per 100,000 (25 – 49 years)
 Standard management: TAH +BSO + PLND +/- Para-aortic
LND

Endometrial Cancer
 Fertility preserving options
 Hormonal treatment
 Patient selection
 Well-differentiated endometrioid AdenoCA confirm by expert
pathology review
 Disease limited to endometrium without myometrium
 Absence of any suspicious or metastatic disease
 Absence of LVSI
 No contraindication to medical therapy
 Strong desire to preserve fertility (understanding of fertility-
preserving – not standard of care)

Endometrial Cancer
 Oral Progesterone (Megestrol acetate,
medroxypogesterone acetate)
 LNG – IUD
 MOA: inhibit estrogen receptor function and endometrial
cell mitosis, promote apoptosis
 Duration: at least 6 months
 Meta-analysis: improved outcomes (IUD LNG > oral
progesterone)

Endometrial Cancer
 Follow up
 Every 3-6 months (endometrial sampling)
 Oncologic Outcomes
 Persistent disease (25 %): Hysterectomy
 Partial response (25%): Medication for additional 3 – 6
months
 Complete response (50 %) : Encourage fertility treatment

Endometrial Cancer
 Recurrence rate: 40 % (15 months)
 Encourage to have pregnancy using ART
 Obstetrical Outcomes:
 Successful pregnancy  significant reduced risk of
recurrence
 IVF doesn’t increase the risk of recurrence
 5 DFS (ovulation induction = spontaneous conception)

Endometrial Cancer

Endometrial Cancer
(NCCN / Summary)

Ovarian Cancer
 Leading cause of death from gynecologic malignancies in western countries
 Majority in postmenopausal age
 Incidence
 20 – 49 year = 1.6 -16 per 100,000
 < 20 years = 0.7 – 1.4 per 100,000
 Standard management:
 Exploratory laparotomy + FS of ovarian tumor
 If invasive – TAH + BSO + debulking omentectomy + PLND + Para-
aortic LND, multiple peritoneal washings and biopsies

Ovarian Cancer
 Comprehensive surgical staging –a mainstay of the
conservative surgical approach
 Removal of ipsilateral adnexa
 Preservation of uterus and contralateral adnexa
 Omentectomy and multiple peritoneal biopsies
 Evaluation of retroperitoneal space through pelvic and para-
aortic lymphadenectomy

Ovarian Cancer
 Indications:
 Epithelial ovarian cancer
 Stage IA, grade I, Serous/mucinous/endometrioid variety
 Not for
 clear cell, small cell and anaplastic tumors,
 high grade serous/mucinous/endometrioid variety
 Hereditary syndrome (BRCA)
 Synchronous endometrial cancer
 Stage > 1 or grade 3

Ovarian Cancer
 Borderline / low malignant potential tumors (BOT)
 10-15 % EOC (1/3rd of ovarian cancer < 40 years)
 Suitable candidate for FSS (excellent prognosis even at an advanced
stage)
 Recurrence (0-25 %, not affect survival rate)
 Fertility preserving procedures
 Cystectomy: Not recommended (40 % relapse rate)
 Bilateral BOT: unilateral SO + contralateral cystectomy
 Routine biopsy of a contralateral healthy ovary is not
recommended
 LND: lymphadenomegaly or peritoneal spread

Ovarian Cancer
 Borderline / low malignant potential tumors (BOT)
 Follow up
 Every 6 months (0-3 years), then yearly
 Prolong F/U: Late recurrence
 Oncologic outcomes
 Survival rate: 99 % (stage 1) to 89 % (stage 3)
 Recurrence rate: 0 - 25 %

Ovarian Cancer
 Germ-Cell Tumor (GCT)
 3 -5 % of ovarian tumor
 Age: < 20 years
 Good prognosis (even for extraperitoneal spread),
 Good response to chemotherapy (good candidate for FS options)
 OS: not affected by FS options
 Relapse: Grade II/III, Advanced stages
 Adjuvant therapy (BEP):
 excellent cure rate 95 % for early stage,
 less toxic to ovaries,
 endocrine function intact

Ovarian Cancer
 Sex-cord Stromal tumors
 Rare neoplasms
 Common at a young age
 Fertility-Preserving Procedure:
 Unilateral salpino-oophorectomy + peritoneal surgical staging (safe
alternative to radical surgery)
 LND: not favorable according to literature
 Further studies are required to evaluate the safety of the conservative
approach and to define obstetrical outcomes

Conclusion
 Fertility preservation options for early-stage gynecological cancers indicate
oncological safety.
 Enables cancer patients at a young age to complete their family without
compromising the oncological outcome
 Patient selection and counseling are crucial.
 Further studies are needed to investigate the role of fertility-sparing treatment
in high-grade cancers and obstetrical outcomes in rare gynecologic tumors.

References
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 Gershenson DM. Contemporary treatment of borderline ovarian tumors. Cancer Invest 1999;17(3):206-10.
 Gershenson DM. Management of ovarian germ cell tumors. J Clin Oncol 2007;25(20):2938-43.
 Gien LT, Covens A. Fertility-sparing options for early stage cervical cancer. Gynecol Oncol 2010;117(2):350-357.
 Lai CH, Chang TC, Hsueh S et al. Outcome and prognostic factors in ovarian germ cell malignancies. Gynecol Oncol
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 Larson DM, Johnson KK, Broste SK et al. Comparison of D&C and office endometrial biopsy in predicting final histopathologic
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 Muruyaesu N, Schmid P, Dancey G et al. Malignant ovarian germ cell tumors : Identification of noval prognostic markers and
long-term outcome after multimodality treatment. J Clin Oncol 2006;24:4862-4866.

References
 Oark TJ, Voit D, Gupta JK et al. Accuracy of hysterescopy in the diagnosis of endometrial cancer and hyperplasia: A systematic quantitative
review. JAMA 2002;288:1610-1621.
 Rob L, Pluta N, Skapa P, Robora H. Advances in fertilitysparing surgery for cervical cancer. Expert Rev Anticancer Ther 2010;10(7):1101-
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 Tangjitgamol S, Manusizivithaya S, Hanprassertpong J. Fertility sparing in endometrial cancer. Gynecol Obstet Invest 2009;67:250-268.
 Ramirez PT, Pareja R, Rendon GJ, Millan C, Frumovitz M, Schmeler KM. Management of low-risk early-stage cervical cancer: should
conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care? Gynecol Oncol. 2014
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 Rob L, Pluta M, Skapa P, Robova H. Advances in fertilitysparing surgery for cervical cancer. Expert Rev Anticancer Ther. 2010;10(7):1101-
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 Rob L, Skapa P, Robova H. Fertility-sparing surgery in patients with cervical cancer. Lancet Oncol. 2011;12(2):192-200.
 Reade CJ, Eiriksson LR, Covens A. Surgery for early stage cervical cancer: how radical should it be? Gynecol Oncol. 2013;131(1):222-30.
 Gien LT, Covens A. Fertility-sparing options for early stage cervical cancer. Gynecol Oncol. 2010;117(2):350-7.
 Rodolakis A, Biliatis I, Morice P, Reed N, Mangler M, Kesic V, Denschlag D. European Society of Gynaecological Oncology Task Force for
Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients. Int J Gynecol
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 Morice P, Denschlag D, Rodolakis A, Reed N, Schneider A, Kesic V, Colombo N; Fertility Task Force of the European Society of
Gynaecologic Oncology. Recommendations of the Fertility Task Force of the European Society of Gynaecologic Oncology about the
conservative management of ovarian malignant tumors. Int J Gynecol Cancer. 2011;21(5):951-63.
 Denschlag D, von Wolff M, Amant F, Kesic V, Reed N, Schneider A, Rodolakis A. Clinical recommendation on fertility preservation in
borderline ovarian neoplasm: Ovarian stimulation and oocyte retrieval after conservative surgery. Gynecol Obstet Invest. 2010;70(3):160-5.
 Thomakos N, Trachana SP, Rodolakis A, Bamias A, Antsaklis A. Less Radical Surgery for Fertility Preservation in Patients with Early-Stage
Invasive Cervical Cancer Contemporary Problematics. Gynecol Obstet 2013;3:165.

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Fertility Preservation for Gynecologic Cancer Patients

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