July 26, 2022 2 to 3 PM

OVARIAN CANCER
AT THE IN PREGNANCY
A Multidisciplinary Conference
Management Plan I Pregnancy and Delivery Considerations I

CROSSROA
I Bioethical Issues I

PRESENTO MODERAT
R OR

DS
NICOLE BALAGTAS DR. VENICE LAWAS
 July 26, 2022

A Case of
Ovarian Squamous Cell Carcinoma
Arising in a Mature Cystic Teratoma
in Pregnancy
PERPETUAL SUCCOUR HOSPITAL July 26, 2022

SPEAKERS

Dr. Raymond Sulay Dr. Imma Lee Pua Dr. Dahlia Go

Gynecologic Oncology Perinatology Neonatology
OBJECTIVES
• To present a case of a 35-year old G1P0 patient 22 weeks age of
gestation diagnosed with ovarian squamous cell carcinoma
arising in a Mature Cystic Teratoma

• Discuss the multidisciplinary approach to ovarian cancer in

pregnancy

• Discuss prognosis

• Discuss bioethical issues invloved in the case

 The Case
•35 year old
•G1P0
•22 weeks AOG
•incidental finding of ovarian new
growth on prenatal check-up
 PAST MEDICAL HISTORY
•No known comorbidities

PERSONAL AND SOCIAL HISTORY

•Non-smoker
•Non-alcoholic beverage drinker
•No history of illicit drug use
History
FAMILY HISTORY
no history of cancer
 FOUR WEEKS PRIOR
• Pre-natal check – up

• Transvaginal ultrasound:
⚬ single live intrauterine pregnancy 15 1/7 weeks
⚬ Huge pelvoabdominal complex mass with low-level echoes
interspersed with fine hyperechoic lines & dots within,
probably right ovary (13.2 x 12.5 x 7.8 cm)

History of Present
• CA 125: 22.3 g/L

Illness
• No abdominal pain, vaginal bleeding, change in bowel or bladder
habits
 THREE WEEKS PRIOR
• 16 weeks AOG

• Initially seen at our institution

• Underwent video-assisted laparoscopy, right salpingo-

oophorectomy with frozen section

History of Present
Illness
 Gross Findings

• No ascites was noted.

• Right ovary converted into a 14 x 13 cm mass with

serous fluid, sebaceous material and hair on

accidental rupture.
Introperatively • Cut section revealed abundant hair and 3 teeth.

• The right fallopian tube was stretched out on the

mass.

• The left fallopian tube and ovary were grossly normal.

 Gross Findings

• No ascites was noted.

• Right ovary converted into a 14 x 13 cm mass with

serous fluid, sebaceous material and hair on

accidental rupture.
Introperatively • Cut section revealed abundant hair and 3 teeth.

• The right fallopian tube was stretched out on the

mass.
Frozen Section
• The left fallopian tube and ovary were grossly normal.
MATURE CYSTIC TERATOMA
 Squamous cell carcinoma arising
in a mature cystic teratoma

• Island composed of dysplastic squamous epithelial

Final
cells. The surrounding sheets of epithelial cells are
HIstopathology markedly pleomorphic, possess enlarged, ovoid to
irregular nuclei, irregularly clumped chromatin,
conspicuous acidophilic nucleoli, and scanty
cytoplasm with indistinct cell borders
 • 21 weeks age of gestation
• Came in for prenatal check-up
• Latest
hgb
labs: 10.2 (low) FBS 80

On Follow-up hct 29.8

hba1c 5.1

WBC 12.4

Neutrophils 91

platelet 191
 • Iron twice daily
• Aspirin 100mg 1x/day
• For congenital anomaly scan

On follow-up
• Advised on her treatment plan
• G1P0 22 1/7 weeks AOG, not in labor
• Squamous cell carcinoma arising in a mature
cystic teratoma, right ovary, stage IC1;
• Status post video-assisted laparoscopy, right
salpingo-oophorectomy with frozen section
of ovarian mass under general endotreacheal
anesthesia
• Advanced maternal age
• Mild Anemia

FINAL DIAGNOSIS
 Ovarian Cancer
Introduction
• 2nd most common malignancy of the lower part of the female genital tract
• leading cause of death from gynecologic cancer

• GERM CELL TUMORS ARE MOST COMMON TYPE IN YOUNG WOMEN

• The most common germ cell tumor is the benign cystic teratoma (dermoid)
• overall, 2% to 3% of germ cell tumors are malignant
COMPREHENSIVE GYNECOLOGY, 8TH EDITION
 Mature Cystic Teratoma

• The risk of malignant transformation is markedly increased in

postmenopausal women.
<2%

• MALIGNANT DEGENERATION occurs in the squamous epithelial elements

• Poor prognosis with spread beyond the confines of the ovary
• Aditional therapy for squamous cell carcinoma with radiation therapy,
chemotherapy, or both is used.
COMPREHENSIVE GYNECOLOGY, 8TH EDITION
 • 35 years old

CASE • Primigravid

CORRELATE
• 21 weeks age of gestation
 OVARIAN CANCER IN PREGNANCY

• Balancing the benefit of treatment for the mother while minimizing harm to the fetus

• Pregnancy apparently does not alter the prognosis

• Management is similar to that of nonpregnant women, modified depending on:
￭ Desire for pregnancy continuation
￭ Gestational age at which treatment is considered

• Standard management: COMPLETE SURGICAL EXCISION and staging

 MATURE CYSTIC TERATOMA WITH
MALIGNANT TRANSFORMATION
• STAGE of the disease is the most important prognostic factor

• According to Chen et al, 5-year survival rate in stage I is 95%, and 33.8, 20.6, and 0%

for stages II, III, and IV, respectively

• Better prognosis when confined to the ovary and excised without spillage of the contents

• In cases of spillage, the reported 5-year survival is 63% (Blaustein's, Chapter 16)
 PROGNOSIS AND TREATMENT

• STAGE of the disease is the most important prognostic factor

• According to Chen et al, 5-year survival rate in stage I is 95%, and 33.8, 20.6, and 0%

for stages II, III, and IV, respectively

• Better prognosis when confined to the ovary and excised without spillage of the contents

• In cases of spillage, the reported 5-year survival is 63% (Blaustein's, Chapter 16)
Our patient is at 5-year survival Post-operative
STAGE IC1 is 63% treatment?
Chemotherapy in Pregnancy
BEP (bleomycin, etoposide, cisplatin)
Mancari et al, 2014. Treatment options for pregnant women with ovarian tumors.

• fetal growth restriction

• cerebral atrophy with
ventriculomegaly
• polyhydramnios
• neonatal creatinine
elevation
• preterm labor
• myelosuppression
Chemotherapy in Pregnancy
A favorable maternal and neonatal outcome following chemotherapy with
etoposide, bleomycin, and cisplatin for management of grade 3 immature
teratoma of the ovary
Fatemeh Ghaemmaghami, Fatemeh Abbasi, Akram Ghahghai Nezam Abadi
J Gynecol Oncol Vol. 20, No. 4:257-259, December 2009 DOI:10.3802/jgo.2009.20.4.257

• A 25-year old primigravid woman presented with an ovarian mass

• At 21 weeks AOG: laparotomy, right oophorectomy and biopsy of the left ovary and

omentum

• Received 3 cycles of 20 IU/m2 bleomycin, 100 mg/m2/day of etoposide, and 20

mg/m2/day cisplatin for 5 days a week.

• Cesarean section was planned for the patient at the 36th week

• After the end of the 3rd course, ultrasound revealed oligohydramnios with estimated fetal

weight in the 5th percentile.

A favorable maternal and neonatal outcome following chemotherapy with
etoposide, bleomycin, and cisplatin for management of grade 3 immature
teratoma of the ovary
Fatemeh Ghaemmaghami, Fatemeh Abbasi, Akram Ghahghai Nezam Abadi
J Gynecol Oncol Vol. 20, No. 4:257-259, December 2009 DOI:10.3802/jgo.2009.20.4.257

• After counseling with perinatalogist, pregnancy was terminated.

• Underwent cesarean section and complete surgical staging was done.

• A male baby with normal appearance with a mild hypospadia was born. The weight of the

baby was two kilograms with an Apgar score of 9-10 at 15 minutes.

• Ultrasound of the baby's brain and kidney were normal at his first month of age.

• Biopsy of the omentum, right salpinx, lymph nodes, and peritoneal samples were normal.

• AFP and CA 125 of serum measurements and ultrasound and CT of the pelvic and

abdominal organs did not show any evidence of tumor recurrence after one year.
Chemotherapy for ovarian cancer during pregnancy: A systematic review
and meta-analysis of case reports and series
Jiang X, Ye Z, Yu W, Fang Q, Jiang Y.
J Obstet Gynaecol Res. 2021 Oct;47(10):3425-3436. doi: 10.1111/jog.14957. Epub 2021 Aug 2. PMID: 34342108.

• 40 ovarian cancer cases received chemotherapy during pregnancy

• During follow-up: 7/37 (18.9%) women had a relapse and 4 of the 7 (57.1%) died of recurrence
• Forty-one newborns were delivered from 40 pregnant women.
⚬ 34/41 (82.9%) were completely healthy at birth and on follow-up (0.18-160 months).
⚬ One newborn died 5 days after birth due to multiple congenital malformations
⚬ One developed Tourette's syndrome, aphasia, Asperger's syndrome as well as speech delay

• Conclusions:
⚬ Efficacy and safety of chemotherapy for ovarian cancer during pregnancy, especially for early-stage
⚬ Cisplatin or carboplatin is suggested to be used as monotherapy to reduce adverse effects.
Efficacy and Safety of Platinum-Based Chemotherapy for Ovarian Cancer
During Pregnancy: A Systematic Review and Meta-Analysis
Pei Y, Gou Y, Li N, Yang X, Han X, Huiling L.
Oncol Ther. 2022 Jun;10(1):55-73. doi: 10.1007/s40487-021-00179-9. Epub 2021 Dec 4. PMID: 34865206; PMCID: PMC9098723.

• A total of 43 studies including 55 cases of ovarian cancer during pregnancy

• 54.17% had early-stage disease, the remaining had advanced stages (II, III, & IV)
• The mean age at diagnosis was 29.31 years, and mean gestational age of 16.05 weeks
• The mean GA at chemotherapy administration was 17.42 weeks

• 55 women gave birth to 56 newborns, including a pair of twins

• One child who died 5 days after delivery due to a congenital abnormality
• 5 cases of recurrence
• 1 patient died 29 months after diagnosis
Pregnancy Monitoring and Delivery Considerations
Wolters V, Heimovaara J, Maggen C, Cardonick E, Boere I, Lenaerts L, Amant F. Management of pregnancy in women with cancer. Int J Gynecol
Cancer. 2021 Mar;31(3):314-322. doi: 10.1136/ijgc-2020-001776. PMID: 33649001; PMCID: PMC7925815.

• serial assessment of fetal well-being and fetal growth

• Dependent on stage and gestational age

• Following surgery, early stage disease can be delivered at or near term (≥37 weeks’ gestation)

with a plan for vaginal delivery.

• Advanced disease may require preterm delivery and possible planned laparotomy for

cesarean delivery and interval debulking [92].

Pregnancy Monitoring and Delivery Considerations
WOLTERS V, HEIMOVAARA J, MAGGEN C, CARDONICK E, BOERE I, LENAERTS L, AMANT F. MANAGEMENT OF PREGNANCY IN WOMEN WITH CANCER.
INT J GYNECOL CANCER. 2021 MAR;31(3):314-322. DOI: 10.1136/IJGC-2020-001776. PMID: 33649001; PMCID: PMC7925815.

• Currently, the majority of providers taking care of pregnant women with malignancy prefer preterm

delivery, despite the neonatal consequences.

• In one study, induction of labor or primary cesarean delivery was performed in over 70% of cases, with

maternal malignancy (as opposed to an obstetrical indication) documented as the indication in 76.7% [7].

• If delivery is anticipated prior to 34 weeks’ gestation, antenatal steroids should be administered for fetal

lung maturity.

• If maternal disease is stable, delivery at or beyond 37 weeks’ is preferred and is often possible.
Pregnancy Monitoring and Delivery Considerations
Wolters V, Heimovaara J, Maggen C, Cardonick E, Boere I, Lenaerts L, Amant F. Management of pregnancy in women with cancer. Int J Gynecol Cancer. 2021
Mar;31(3):314-322. doi: 10.1136/ijgc-2020-001776. PMID: 33649001; PMCID: PMC7925815.

• Ideally, chemotherapy should be stopped 2 to 3 weeks prior to delivery to allow for the

recovery of the fetal and maternal bone marrow.

• Minimize risk for infection & sepsis in both the mother and the baby[47,48].

• Apontaneous preterm labor can occur, especially after 34 weeks’ gestation, it is often

recommended that chemotherapy not be administered beyond the 33rd week of gestation

[43].
Postpartum Considerations

• Histologic evaluation of the placenta

• For women who require chemotherapy or hormonal therapy following delivery, breast feeding is

contraindicated [5,55].

• If desirous of future pregnancy

⚬ `Wait for at least a 2 year disease-free interval after treatment, as this is the most likely time-

frame for a recurrence [5]. However, because overall survival is predicted by the 5-year disease-

free interval, patients should be encouraged to delay pregnancy for 5 years

 MEDICAL PATIENT PREFERENCES
INDICATIONS
The patient is a pregnant 35 year old, G1P0 at 22 weeks AOG
diagnosed with Ovarian squamous cell carcinoma arising in a
mature cystic teratoma stage IC1

GOAL: Prevent recurrence of ovarian cancer, and fetal

preservation without delay in treatment

Treatment options: delay treatment, adjuvant BIOETHIC

chemotherapy S
QUALITY OF LIFE CONTEXTUAL FEATURES
 MEDICAL PATIENT PREFERENCES
She understands the possible risks and complications as well as
INDICATIONS
The patient is a pregnant 35 year old, G1P0 at 22 weeks AOG
the management if these arise.
diagnosed with Ovarian squamous cell carcinoma arising in a
mature cystic teratoma stage IC1
Still hesitant in making an informed decision or consent, although
she wishes to optimize the best possible treatment option
GOAL: Prevent recurrence of ovarian cancer, and fetal
Would like to discuss it first with her partner and family
preservation without delay in treatment

Treatment options: delay treatment, adjuvant BIOETHIC

chemotherapy S
QUALITY OF LIFE CONTEXTUAL FEATURES
 MEDICAL PATIENT PREFERENCES
She understands the possible risks and complications as well as
INDICATIONS
The patient is a pregnant 35 year old, G1P0 at 22 weeks AOG
the management if these arise.
diagnosed with Ovarian squamous cell carcinoma arising in a
mature cystic teratoma stage IC1
Still hesitant in making an informed decision or consent, although
she wishes to optimize the best possible treatment option
GOAL: Prevent recurrence of ovarian cancer, and fetal
Would like to discuss it first with her partner and family
preservation without delay in treatment

Treatment options: delay treatment, adjuvant BIOETHIC

chemotherapy S
QUALITY OF LIFE CONTEXTUAL FEATURES
• Post-operative adjuvant treatment prevents recurrence
of ovarian cancer
• possibility of progression and/or recurrence of cancer if treatment
is delayed or even when treatment is initiated early
• Treatment may render her weak & immunosuppressed that she
will not be able to emotionally & physically support her child.
• Effects of antineoplastic agents during the second trimester
• These could potentially alter not only her's but also of her child's
quality of life.
 MEDICAL PATIENT PREFERENCES
She understands the possible risks and complications as well as
INDICATIONS
The patient is a pregnant 35 year old, G1P0 at 22 weeks AOG
the management if these arise.
diagnosed with Ovarian squamous cell carcinoma arising in a
mature cystic teratoma stage IC1
Still hesitant in making an informed decision or consent, although
she wishes to optimize the best possible treatment option
GOAL: Prevent recurrence of ovarian cancer, and fetal
Would like to discuss it first with her partner and family
preservation without delay in treatment

Treatment options: delay treatment, adjuvant BIOETHIC

chemotherapy S
QUALITY OF LIFE CONTEXTUAL FEATURES
• Post-operative adjuvant treatment prevents recurrence
of ovarian cancer • BENEFICENCE
• possibility of progression and/or recurrence of cancer if treatment
is delayed or even when treatment is initiated early • MALEFICENCE
• Treatment may render her weak & immunosuppressed that she
• AUTONOMY
will not be able to emotionally & physically support her child.
• Effects of antineoplastic agents during the second trimester • Perceived long-term significant financial considerations
• These could potentially alter not only her's but also of her child's
• No religious factor was brought up by the mother.
quality of life.
 INSIGHTS
FROM OUR
REACTORS