마더세이프라운드 - 임신중부인암(이인호 교수)

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

Issues in Pregnancy

• Is termination of the pregnancy necessary

or advantageous?

• Will the malignant neoplasm or the therapy

for it affect the fetus?

• Should therapy be deferred and initiated at

the termination of the pregnant stage?

• Should patients be advised against future

pregnancies?

Finding answers to these questions is difficult!

Cancer and Young women

Site Occurrence in women

aged 15-44 years (%)

Cervix

Ovary

All genital

Lymphomas

Thyroid

Bones and joints

Melanoma

Breast

Leukemia

Soft tissues

35

15

18

23

50

27

27

15

10

20

Incidence of Cancer in Pregnancy

Site Estimated incidence Per

1000 pregnancies

Cervix uteri

Noninvasive

Invasive

Breast

Melanoma

Ovary

Thyroid

Leukemia

Lymphoma

Colorectal

1.3

1.0

0.33

0.14

0.10

Unknown

0.01

0.01

0.02

Cervical Cancerin Pregnancy

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

Five-year survival rates

AuthorPregnant

survival (%)

Non-pregnant

survival (%)

Creasman (1970)

Stage I

Stage II

85

60

80

70

Sablinska (1977)

Stage I

Stage II

72

54

76

56

Lee (1981)

Stage Ib - surgery

Stage Ib - radiation

93

80

91

88

Nisker and Shubat (1983)

Stage Ib 70 87

Sivanesaratnam (1993)

Surgery 78 92

Pregnancy has not been shown convincingly to

have an adverse effect on cancer of the cervix!

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

Symptom

• Usually asymptomatic, detected during

routine Pap smear

• Vaginal bleeding and discharge may be

mistaken for pregnancy complications

• Pelvic pain : less frequent

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

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 .

Diagnosis

• Cervical conization during pregnancy iscrucial in diagnosis and staging of MIC

• Complications

– Hemorrhage 2-13%

– Fetal loss : 17%-50%, <10% in 2nd and 3rd

– PMRM, preterm labor, infection, lacerationand stenosis

– Fetal Salvage rate : 89-95%

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.

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

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

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

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

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

Summary of t.t Delays

Author N. Stage Delays outcome

Monk et al(1992)

3 IB Mean24wk

DOD

Duggan etal (1993)

8 IA-IB Mean20.6w

NED

Soroskyet al (1996

8 I Mean15.6w

NED

3rd trimester Treatment

• Wait for few weeks till fetal maturity thenapply definitive therapy

• Surgery in 89% may be coordinated withfetal delivery and completed as a 1-stageoperation.

• If R.T..external beam immediately afterdelivery followed by intracavitary radiation

Effect of Mode of DeliveryAuthor C.S %survival vaginal %survival

Creasman et al(1970)

9 89% 15 87%

Lee et al (1981)

12 90% 11 89%

Nisker et al (1983)

14 64% 17 65%

Van Der Vang et al (1995)

28 78% 16 67%

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.

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.

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

Ovary Cancerin Pregnancy

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

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%

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 laborLeiserowitz 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

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

Management of an ovarian mass in pregnancy

Size<10cm

Simple, Unilateral

No evidence of Ascites

Persists or growth

Follow to 18 weeks

Persistent at 18 weeks or any 30%-50% increase in size of mass at any point in gestation

Follow with ultrasound

Surgical exploration

Size>5cm

Complex, papilations

and/or Bilateral

Surgical exploration

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

Adnexal Masses in Pregnancy

(Cheil General Hospital)

Materals

• 1996년 1월 – 2001년 12월• 255명 / 50,126 분만 (0.5%)• 평균연령 : 28.7세• 평균크기 : 9.5cm• 수술시기

– 분만전 (160명, 62.7%) : 15.2 주– 분만시 (95명, 37.3%)

• 응급수술 (42명,17.6%)– 난소염전 (30명)– 난소파열 (5명)– 동통 (7명)

Histologic Diagnosis of

Adnexal Mass

5.5%

(14/255)

Fetal Outcomes

*Spontaneuos abortion (3), Artificial abortion (2)** Intrauterine fetal death (1)

Ovary Cancer

and Chemotherapy

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

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

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.

Characteristics of patients

Histologic characteristics

Surgical management

Histology of tumor in Literature

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.

• 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

Adjuvant Chemotherapy (n=8)

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!

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.

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

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

Endometrial Cancerin Pregnancy

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

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.

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