1. Gynecologic Cancer
in Pregnancy
In Ho Lee M.D.,
Department of Obstetrics and Gynecology,
Cheil General Hospital and Women's Healthcare Center,
Kwandong University, College of Medicine, Seoul, Korea
2. Issues in Pregnancy
• Is termination of the pregnancy necessary
or advantageous?
• Will the malignant neoplasm or the therapy
for it affect the fetus? questions is difficult!
Finding answers to these
• Should therapy be deferred and initiated at
the termination of the pregnant stage?
• Should patients be advised against future
pregnancies?
3. Cancer and Young women
Site Occurrence in women
aged 15-44 years (%)
Cervix 35
Ovary 15
All genital 18
Lymphomas 23
Thyroid 50
Bones and joints 27
Melanoma 27
Breast 15
Leukemia 10
Soft tissues 20
4. Incidence of Cancer in Pregnancy
Site Estimated incidence Per
1000 pregnancies
Cervix uteri
Noninvasive 1.3
Invasive 1.0
Breast 0.33
Melanoma 0.14
Ovary 0.10
Thyroid Unknown
Leukemia 0.01
Lymphoma 0.01
Colorectal 0.02
6. Diversity of Opinion
• Cervical cancer prevents pregnanacy
↔ Pregnancy prevents cervical cancer
• Pregnancy accelerates cervical cancer
↔ Pregnancy slows the growth of cervical cancer
• Young age is a good prognostic indicator
↔ Youth is a detriment
• High estrogen levels predispose to cervical cancer
↔ High estrogen content controls cervical cancer
• Radiotherapy is the treatment of choice
↔ Primary radical surgery is the best treatment
7. Five-year survival rates
Pregnant Non-pregnant
Author
survival (%) survival (%)
Creasman (1970)
Stage I 85 80
Stage II 60 70
Sablinska (1977)
Stage I 72 76
Pregnancy has
Stage II
not been shown convincingly to
54 56
Lee (1981) adverse effect on cancer of the cervix!
have an
Stage Ib - surgery 93 91
Stage Ib - radiation 80 88
Nisker and Shubat (1983)
Stage Ib 70 87
Sivanesaratnam (1993)
Surgery 78 92
8. Incidence
• The incidence of CIN varies but it is generally
between 1% to 8% of abnormal cytology.
• Invasive cancer is the most common solid
tumor during pregnancy
• Fortunately its incidence is 0.2% to 0.9% of
all pregnancies
• 1.4% of all cases of cervical cancer
9. Symptom
• Usually asymptomatic, detected during
routine Pap smear
• Vaginal bleeding and discharge may be
mistaken for pregnancy complications
• Pelvic pain : less frequent
10. Cervical cancer screening
• Cervical cancer peaks between age 30
to 49 years
• The mean age of pregnant women with
invasive cervical cancer 31.8y.
• Significant numbers diagnosed in 2nd or
3rd trimester
• Efficacy and safety of screening is well-
documented
11. Diagnosis
• Colposcopy is safe and well tolerated and
should be used to evaluate abnormal Pap
smear
• Any suspicious lesion should be biopsed
• Overall risk of biopsy-related complications
is approximately 0.6%
: usually mild bleeding .
12. Diagnosis
• Cervical conization during pregnancy is
crucial in diagnosis and staging of MIC
• Complications
– Hemorrhage 2-13%
– Fetal loss : 17%-50%, <10% in 2nd and 3rd
– PMRM, preterm labor, infection, laceration
and stenosis
– Fetal Salvage rate : 89-95%
13. Workup
• Physical examination
• Cervical biopsy
• Conization
• Chest x-ray with abdominal shield
• Since about 83% of cases are stage I, cys
toscopy and proctoscopy are eliminated
: also I.V.U and Enema.
14. Treatment of CIN
• No indications for immediate treatment of cases
with CIN during pregnancy
• Pap smear or Colposcopy every trimester
• Vaginal Delivery with higher rate of regression
at 6-week examination compared to Caesarean
delivery
• Definitive treatment : 6 weeks postpartum
15. Treatment of invasive cancer
• For a microinvasive cancer of cervix, excision can
be performed
– The outcome is usually good, the pregancy can proceed
and a vaginal delivery can be anticipated
• Invasive cancer during pregnancy is curable
• Treatment is clear in the 1st and 3rd trimester but
less clear in the 2nd trimester
• Two modalities used are surgery or RT as in non-p
regnant
16. First trimester(1-12weeks)
• Fetal salvage is not feasible in women rece
iving treatment for invasive cancer
• The maternal risk from delaying therapy unt
il fetal maturity is excessive
• Surgery with the fetus in situ
17. Second trimester (13-25weeks)
• The period of greater uncertainty
• Fetal salvage is exceedingly rare with high
neonatal mortality rate
• Delaying therapy for several weeks may
subject the mother to the theoretical risk of
disease progression
18. Second trimester (13-25weeks)
• If patient elects to interrupt pregnancy
: The same as in 1st trimester
• If not ..define a target gestational age for fetal
delivery
• Monitor by U/S and MRI for tumor extension
• Documented lung maturity
19. Summary of t.t Delays
Author N. Stage Delays outcome
Monk et al 3 IB Mean DOD
(1992) 24wk
Duggan et 8 IA-IB Mean NED
al (1993) 20.6w
Sorosky 8 I Mean NED
et al (1996 15.6w
20. 3rd trimester Treatment
• Wait for few weeks till fetal maturity then
apply definitive therapy
• Surgery in 89% may be coordinated with
fetal delivery and completed as a 1-stage
operation.
• If R.T..external beam immediately after
delivery followed by intracavitary radiation
21. Effect of Mode of Delivery
Author C.S %survival vaginal %survival
Creasman 9 89% 15 87%
et al(1970)
Lee et al 12 90% 11 89%
(1981)
Nisker et al 14 64% 17 65%
(1983)
Van Der 28 78% 16 67%
Vang et al
(1995)
22. Treatment before 20 weeks
• The ‘standard’ management for stage-1b1 cervical
cancer up to 20 weeks’ gestation would be a radical
hysterectomy with the fetus in situ, and should be
offered as a management option.
• For more advanced disease chemoradiation will be
preferred.
• In early pregnancy spontaneous miscarriage will
usually occur after the woman has received 34–40
Gy, although after 20 weeks’ gestation miscarriage
can be protracted (mean 33–44 days), or may not
occur spontaneously in 60%, so that the uterus will
need to be emptied.
23. Treatment after 20 weeks
• A planned delay to allow fetal viability or even
maturity is also an option, and may not actually
significantly affect her survival.
• A delay of up to 6 weeks for stage-1b2 and 12
weeks for stage-1b1 disease is reasonable,
with careful clinical and/or MRI monitoring of
the woman every 2–4 weeks.
• Steroids can be given with no apparent
adverse effects on the cancer to expedite fetal
lung maturity.
24. Treatment after 20 weeks
• Caesarean section with radical hysterectomy after fetal
viability or maturity is reached with stage-1b disease.
• Radical hysterectomy 48–72 h after vaginal delivery,
assuming labour is not obstructed
– the advantages of reduced blood loss and a better vaginal cuff
with the resected specimen.
• Delaying intervention even further may be an option with
reassurance gained by negative histology following
laparoscopic lymphadenectomy
• Chemotherapy, particulary after the first trimester, is
well tolerated without deterimental effects on the fetus
and appears to be an option for the selected patient
26. Adnexal Masses in Pregnancy
• 0.05-3.2% of live birth
• Mature teratomas and paraovarian or corpus
luteum cysts
• Malignancy rate : 3.6-6.8% in persistent
masses
• Germ cell, stromal, or epithelial tumors of
low malignant potential
• TVS or TAS
• MRI if additional imaging is needed
27. Adnexal Masses in Pregnancy
• CA125
– Peak in the first trimester (7-251 U/ml) and
decrease consistently thereafter
– Low level elevations are not associated with
malignancy
• Surgical removal of persistent masses in the
second trimester
• 51-70% resolve during pregnancy
• Acute complication : less than 2%
28. Adnexal Masses in Pregnancy
• Indication of Surgical Intervention
– A strong suspicion of malignancy and/or large
size (>8-10 cm)
– Symptomatic patients
– An increased risk of torsion/rupture/obstruction
of labor
Leiserowitz GS, Obset Gynecol Surv 2006;61(7):463-70
• Ovarian malignancy has no effect on
pregnancy and pregnancy has no effect on
prognosis of ovarian cancer
• Benign cyst may undergo torsion causing
acute abdomen commonly in puerperium
29. Management
• Benign tumor
– First trimester : observe and follow-up with
ultrasound till second trimester (to reduce risk of
abortion) and then removal
– Second trimester : laparotomy
– Third trimester : Caesarean section and removal
of tumor
• Malignant tumors
: treated as non-pregnant i.e. surgical staging and
cytoreductive surgery
30. Management of an ovarian mass in pregnancy
Size<10cm Size>5cm
Simple, Unilateral Complex, papilations
No evidence of Ascites and/or Bilateral
Follow to 18 weeks Follow with ultrasound
Persists or growth Persistent at 18 weeks or
any 30%-50% increase in
size of mass at any point in
gestation
Surgical exploration Surgical exploration
31. Aspiration of Cyst Fluid
• Poor sensitivity to detect malignancy (25-
82%)
• 25% of cysts recur within 1 yr
• Spillage and seeding of cancer cell into the
peritoneal cavity -> Changing the stage and
prognosis
• Exception
– Clinical and radiolographic evidence of advanced
ovarian cancer and unfit to ungergo surgery
– Permit initiation of neoadjuvant chemotherapy
37. Three stages of
Embryonic development
• The first stage
– The first 2 weeks of life
– Blastocyst is resistant to teratogens
– A surviving blastocyst will not manifest any
organ’s specific abnormalities as a result of
that teratogen
– Early embryonic cells have not differentiated
sufficiently, so if one cell dies, another can
take over
38. Three stages of
Embryonic development
• The second stage
– Organogenesis or the process of organ
differentiation
– The most critical period extends from the 3rd
to 8th weeks of development (5th through 10th
weeks of gestational age) when susceptibility
to teratogenic agents is maximal
– In the human fetus, this period usually ends
by the 13th week of gestation
39. Three stages of
Embryonic development
• The third stage
– characterized by increase in fetal and organ
size
– Brain and gonadal tissue are exceptions
because they continue to differentiate beyond
the second period
– Affect general fetal growth but will not produce
organ-specific morphologic malformations.
45. Adjuvant Chemotherapy (n=8)
• 3 patients received chemotherapy with
fetus in utero
• 5 patients received chemotherapy just after
delivery
• One patient with EOC complicating ectopic
pregnancy received postoperative
chemotherapy.
46. Adjuvant Chemotherapy (n=8)
• Of five patients with germ cell tumor, 3 patients
received it with the fetus in utero (range, 22.8-30.6
weeks of GA) and two patients at 2 weeks after
cesarean delivery with 4 courses of bleomycin,
etoposide and cisplatin (BEP).
• Three patients with EOC received 6 courses of
paclitaxel plus carboplatin at 2 weeks after cesarean
delivery.
• All 26 patients with ovarian cancer complicating
pregnancy were successful in having a full term
delivery
47. Chemotherapy during first
trimester of pregnancy
All cancer chemotherapeutic agents should be
considered teratogenic and should be avoided in the
first trimester of pregnancy if it is at all possible!
48. Chemotherapy during preg in
Literature
• Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Sutcliffe SB,
Koren G. Fetal outcome after in utero exposure to cancer
chemotherapy. Arch Intern Med 1992; 152: 573-6.
• Doll DC, Ringenberg QS, Yarbro JW. Antineoplastic agents and
pregnancy. Semin Oncol 1989; 16: 337-46.
• Arango HA, Kalter CS, Decesare SL, Fiorica JV, Lyman GH, Spellacy
WN. Management of chemotherapy in a pregnancy complicated by a
large neuroblastoma. Obstet Gynecol 1994; 84: 665-8.
• Horbelt D, Delmore J, Meisel R, Cho S, Roberts D, Logan D. Mixed
germ cell malignancy of the ovary concurrent with pregnancy. Obstet
Gynecol 1994; 84: 662-4.
49. Chemotherapy during pregnancy
in Literature
• Huang HP, Fang CN, Kan YY. Chemotherapy for ovarian mucinous
cystadenocarcinoma during pregnancy: a case report. Eur J Gynaecol
Oncol 2004; 25: 635-6.
• Bayhan G, Aban M, Yayla M, Gul T, Yaldiz M, Erden AC. Cisplatinum
combination chemotherapy during pregnancy for mucinous
cystadenocarcinoma of the ovary. Case report. Eur J Gynaecol Oncol
1999; 20: 231-2.
• Mendez LE, Mueller A, Salom E, Gonzalez-Quintero VH. Paclitaxel and
carboplatin chemotherapy administered during pregnancy for advanced
epithelial ovarian cancer. Obstet Gynecol 2003; 102: 1200-2.
• Sood AK, Shahin MS, Sorosky JI. Paclitaxel and platinum hemotherapy
for ovarian carcinoma during pregnancy. Gynecol Oncol 2001; 83: 599-
600
50. Chemotherapy in Pregnancy
• The administration of chemotherapy during the
first trimester can be associated with
morphologic abnormalities and fetal loss
• Chemotherapy administrated in second and third
trimesters appears not to be associated with a
significant risk of structural anomalies, but some
reports suggest an associated with preterm
delivery, fetal death in utero, and intrauterine
growth retardation
• When cytotoxic drugs are used in late pregnancy,
the nadir should be timed to avoid the interval
when delivery is expected
52. Incidence
• Endometrial cancer in association with
pregnancy is extremely rare
– It is a disease mainly of postmenopausal women
– high levels of progesterone in pregnancy would be
expected to antagonize the effect of oestrogen on
the endometrium
• Only 28 cases are reported in the literature
• Diagnosis is usually made following curettage
for persistent bleeding after a miscarriage or
postpartum
53. Management
• The outcome is usually good, and the treatment is
the same as for the nonpregnant woman.
• It may be reasonable to treat conservatively very
early stage, well differentiated endometrial cancer in
young women wishing to retain their fertility.
• High-dose progestin treatment over 6–10 months
with regular sampling allowed five of 10 women to
have babies
• However, at long-term follow-up of nine of them, eight
developed recurrent cancer, although all survived.
