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Cancer in Pregnancy. Jeffrey Stern, M.D. Physician Reaction. Ob/Gyn: Oh No! She has cancer! Med Onc: Oh No! She’s pregnant! Surgeon/Primary Care: Oh No! She’s pregnant and has cancer! Get a Gyn/Onc involved!. Incidence. 1/1000 – 1/1500 term pregnancies

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Cancer in pregnancy

Cancer in Pregnancy

Jeffrey Stern, M.D.


Physician reaction
Physician Reaction

  • Ob/Gyn: Oh No! She has cancer!

  • Med Onc: Oh No! She’s pregnant!

  • Surgeon/Primary Care: Oh No! She’s pregnant and has cancer!

  • Get a Gyn/Onc involved!


Incidence
Incidence

  • 1/1000 – 1/1500 term pregnancies

  • Incidence increasing secondary to delayed childbearing

  • Frequency by cell type (Frequency in reproductive age group)

    • Breast cancer (30%)

    • Lymphoma (10%) / Leukemia (23%)

    • Melanoma (30%)

    • Cervix (35%), Ovary (15%)

    • Bone/soft tissue tumors (25%)

    • Thyroid (50%)


What s different about pregnancy
What’s Different About Pregnancy?

  • Hormones

  • Metabolic Changes

  • Hemodynamics

  • Immunology

  • Increased vascularity

  • Age

  • Few cases – anecdotal experience

  • Inherent bias – breast cancer, ovarian cancer


General considerations
General Considerations

  • Pregancy does not have a proven negative effect on any cancer

  • Maintaining pregnancy after diagnosis

    • Delay of treatment (assume delivery at 34th week)

      • First trimester diagnosis: up to 28 week delay

      • Second trimester diagnosis: up to 22 week delay

      • Third trimester diagnosis: up to 10 week delay


General considerations1
General Considerations

  • Surgery

    • Wait until 16-18 weeks for abdominal surgery. SAB: 40%  3%

    • Don’t remove corpus luteum if possible until the 14th week (progesterone supp. 50mg BID)

    • Deliver at maturity (at around 34 weeks)

    • No proven teratogenic effects of anesthesia


General considerations2
General Considerations

  • Chemotherapy

    • First trimester (organogenesis ends at 12th week)

      • Increase incidence of anomalies and abortion; drug dependent i.e. antimetabolites (MTX)

      • IUGR and preterm labor are common

    • Second and Third trimester

      • Anomalies not increased

      • No increase in incidence of abortion

      • IUGR and preterm labor are common

      • Delay chemotherapy if possible until 16th week (end of the rapid growth phase)


General considerations3
General Considerations

  • Chemotherapy and Breastfeeding

    • Generally not recommended

  • Long-term effects of chemotherapy on children exposed in utero

    • Aviles, et.al. 43 cases with f/u for 3-19 yrs.


General considerations4
General Considerations

  • Radiation Exposure

    • Diagnostic Radiation

      • Avoid “unnecessary” diagnostic pelvic x-rays

      • Use MRI when possible

      • CXR/Mammogram – little risk with shielding

    • Therapeutic Radiation

      • High incidence of abortion and anomalies

        • Dose and trimester dependent


General considerations5
General Considerations

  • Obstetrical Considerations

    • First trimester SONO: if dates?

    • Level 2 SONO at 20 weeks

    • Chromosome analysis

      • Amnio: 15 weeks

      • CVS: Transcervical (except cervix ca) or transabdominal at 10-12 weeks

    • Deliver when mature

      • L/S ratio at 34 weeks

      • Betamethasone


Epidemiology of genital hpv sil cancer in pregnancy
Epidemiology of Genital HPV/SIL/Cancer in Pregnancy

  • Up to 40% of reproductive age women have HPV

  • 2.0-6.5% cases of CIN/SIL occur in pregnant women

  • 13,500 cases of cervical ca. & 4,000 deaths/year in U.S.

  • 25% of women with cervical cancer are < 36 y.o.

  • 1-13 cases of cervical cancer for every 10,000 pregnancy

  • 1.9% of microinv. cervical ca. occurs in pregnancy

  • Stage for stage – prognosis is not effected by pregnancy


Screening for cervical cancer sil
Screening for Cervical Cancer/SIL

  • Symptoms of ca. similar to physiol. changes of preg.

  • Often a delay in diagnosis (fear of biopsies)

  • Pap smear at registration and 8 weeks postpartum

    • Ectocervical scrape

    • Endocervical swab / brush – risky

    • HPV typing

  • Pap less accurate in pregnancy: increased false negative rate

    • Blood, inflammation

    • Failure to sample SCJ

    • Concern about bleeding

    • Difficult to see cervix

    • Condom

    • Absence of endocervical cells



Diagnosis of sil and cervical cancer
Diagnosis of SIL and Cervical Cancer

  • Careful palpation of cervix: no induration or enlargement

  • Biopsy all suspicious lesions: even if Pap/HPV are normal

  • Abnormal Pap:

    • Ascus/LSIL – HPV negative – repeat post partum

    • Colpo-directed biopsy for HSIL

    • HPV+/HSIL – Colpo

  • Don’t defer biopsy because of fear of bleeding or preterm labor. First trimester easiest.

  • Control bleeding with:

    • Pressure

    • Monsel’s solution (Ferric subsulfate)

    • Silver nitrate


Management of cervical sil
Management of Cervical SIL

  • Satisfactory Colposcopy

    • Follow with paps and colpo more frequently if HPV 16/18 positive

    • Vaginal delivery

    • Re-evaluate 6-8 weeks postpartum

    • Low grade SIL (50%) regress postpartum (Delivery route seems to matter)

    • High grade SIL(30%) regress postpartum


Management of cervical sil1
Management of Cervical SIL

  • Cone biopsy in pregnancy

    • Indications

      • Unsatisfactory colposcopy/Pap: scc, HSIL

      • Adenocarcinoma in situ

      • Microinvasive SCC

    • Perform at 16-18 weeks

    • Risks

      • Abortion: 5%

      • Hermorrhage

        • Immediate: 9%

        • Delayed: 4%

    • Technique

      • Local wedge resection

      • Shallow cone

      • LEEP

      • Circumferential figure 8 sutures at cervical-vaginal junction


Management of cervical sil2
Management of Cervical SIL

  • HPV+/HSIL on Pap: No Lesion Visible on Colposcopy

    • Reinspect: Vulva, Vagina and Cervix

    • Lugol’s: Vagina and Cervix

    • Review Cytology

    • Consider Random Biopsies: 6 and 12 o’clock

    • Careful Follow-up: Pap and Colpo


Vulvar or vaginal condylomata or sil in pregnancy
Vulvar or Vaginal Condylomata or SIL in Pregnancy

  • Warts and SIL often enlarge rapidly in pregnancy

  • No treatment unless symptomatic

  • Often regresses dramatically postpartum

  • Treat if symptomatic or interferes with vaginal del., i.e., disease on perineal body or posterior fourchette

  • Treatment options

    • TCA

    • Podophyllin

    • Aldara

    • 5-Fu cream

    • Laser

    • Excision: scalpel; LEEP


Cervical cancer in pregnancy
Cervical Cancer in Pregnancy

  • Work-up

    • MRI of pelvis/abdomen

    • Chest X-ray

    • Carcinoembryonic Antigen (CEA)

    • CBC, BUN, Creatine, LFT’s

    • Urine cytology/cystoscopy

    • Stool for occult blood/Sigmoidoscopy – advanced disease


Cervical cancer in pregnancy treatment by stage
Cervical Cancer in Pregnancy: Treatment by Stage

  • Stage IA1 - <3mm invasion; < 7mm wide

    • 1.2% positive nodes

    • Cone biopsy

    • No further treatment necessary; simple hysterectomy

    • Vaginal delivery at term


Cervical cancer in pregnancy treatment by stage1
Cervical Cancer in Pregnancy: Treatment by Stage

  • Stage IA2 (3-5mm inv., no vasc. inv.) 6.3% positive nodes

  • Stage IB – confined to cervix

  • Stage IIA (early) – vaginal extension

    • Vaginal delivery: inc. risk of hemorrhage and cervical laceration

    • Depends on desire for pregnancy

      • First trimester: delay of up to 28 weeks – (degree of risks unknown)

      • Radical hyst. and pelvic LND at diagnosis

      • “Radical” cone biopsy/trachelectomy/cerclage and extraperitoneal pelvic and aortic LND at 16-18 weeks

      • C-Section and Radical hyst. and pelvic LND when mature


Cervical cancer in pregnancy treatment by stage2
Cervical Cancer in Pregnancy: Treatment by Stage

  • Stage IA2, IB, IIA (early) – vaginal extension

    • Second trimester: delay of up to 22 weeks

      • Depends on desire for pregnancy

        • Can probably safely wait until maturity

        • Manage like first trimester

    • Third trimester: delay of up to 10 weeks

      • C-section, Radical hysterectomy and pelvic LND at maturity


Cervical cancer in pregnancy treatment by stage3
Cervical Cancer in Pregnancy: Treatment by Stage

  • Stage IB (bulky) or Stages IIb-IV

    • First trimester – delay of up to 28 weeks

      • Depends on desire for pregnancy

        • Unwanted

          • Whole pelvic radiation therapy/chemotherapy

          • If SAB occurs before XRT is finished – proceed with cesium insertions (about 35 days)

          • Occasionally will need hysterotomy and pelvic LND if no SAB and then cesium insertions; or a “small” radical hyst. and pelvic LND if small residual cervical disease

        • Wanted

          • Consider chemotherapy until maturity at 34 weeks


Cervical cancer in pregnancy treatment by stage4
Cervical Cancer in Pregnancy: Treatment by Stage

  • Stage IB (bulky) or Stages IIb-IV

    • Second trimester – delay of up to 22 weeks

      • Unwanted: pregnancy – Radiation therapy as above (SAB at 45 days)

      • Wanted: pregnancy – consider chemotherapy until maturity

    • Third trimester – delay of up to 10 weeks

      • C-Section at maturity/staging lap; transpose ovaries

      • Start radiation therapy 2 weeks postpartum

      • Consider chemotherapy until maturity


Juvenile laryngeal hpv
Juvenile Laryngeal HPV

  • 3.5 million deliveries in U.S./year

  • Prevalence of HPV: 10-40%

  • Infected pregnant women: 350k - 1.5 million

  • 120 cases annually

  • Risk to infant (1:2,900 – 1:12,500)

  • VAGINAL DELIVERY


Ovarian masses in pregancy
Ovarian Masses in Pregancy

  • Overall incidence

    • 1:500 pregnancies

    • Increased incid. secondary to sonography

  • Incidence of true neoplasms – 1:1,000 pregancies

  • Incidence of ovarian cancer – 1:10,000 – 1:25000 pregancies

  • At C-Section 1:700 – unexpected adnexal mass


Ovarian masses in pregnancy frequency by type
Ovarian Masses in Pregnancy: Frequency by Type

  • Non-neoplastic – 33%

    • Corpus luteum cyst

    • Follicular cyst

  • Neoplastic – Benign – 63%

    • Dermoid (36%)

    • Serous cystadenoma (17%)

    • Mucinous cystadenoma (8%)

    • Others (2%)

  • Neoplastic – Malignant – 5%

    • Low malignant potential (3%)

    • Adenocarcinoma (1%)

    • Germ cell / Stromal tumor (1%)


Management of ovarian masses in pregnancy
Management of Ovarian Masses in Pregnancy

  • Generalizations

    • Symptoms

    • SONO/MRI appearance

    • Size

    • Gestational age

    • Tumor markers

      • B-HCG, AFP, CA-125 all increased in pregnancy

      • CA-125 should be normal after 1st trimester

    • Fear of missing cancer or development of complications

      • Corpus luteum resolves by 14th week

      • Ovarian cysts “benign” by SONO or MRI, < 6 cm, that do not change over time, do not require surgery

      • Cysts greater than 6-8 cm or increase in size are “usually” operated on

      • Cysts which persist after 18th week are “usually” operated on

    • Usually operate at 18 weeks if persisted to minimize fetal loss


Complications of ovarian masses in pregnancy
Complications of Ovarian Masses in Pregnancy

  • Severe pain: 25% of cases

  • Obstruction of labor: 15% of cases – C-Section

  • Torsion: 10% of cases

    • Sudden pain, N&V etc.

    • Most common at:

      • 8-16 week – rapid uterine growth (60%)

      • Postpartum – involution (40%)

  • Hemorrhage: 10% of cases

    • Ruptured corpus luteum

    • Germ cell tumor


Complications of ovarian masses in pregnancy1
Complications of Ovarian Masses in Pregnancy

  • Rupture/tumor dissemination (10%)

  • Anemia

  • Malpresentations

  • Necrosis

  • Infection

  • Ascites

  • Masculinization of female fetus

    • Hilar cell tumor

    • Luteoma of pregnancy

    • Sertoli-Leydig cell tumor


Work up of ovarian cancer
Work-up of Ovarian Cancer

  • Pelvic sono

  • MRI pelvis/abdomen

  • CXR

  • CA-125: elevated in normal pregnancy, should normalize after 12 weeks

  • AFP, B-HCG, LDH – predominantly solid mass

  • LFT’s, BUN, Creat.

  • GI studies only if clinically indicated


Management of ovarian cancer
Management of Ovarian Cancer

  • Prognosis not affected by pregnancy

  • Tumors of Low Malignant Potential – all stages (20%)

  • Adenocarcinoma Stage I, grade 1 or 2 (10%)

  • Germ cell tumors (5%) – may require chemotherapy

  • Gonadal stromal tumors (15%)

  • Surgery at 16-18 weeks if possible

  • Frozen section: beware of inaccuracies

  • Conservative ovarian surgery

    • Adnexectomy

    • Oophorectomy

    • Cystectomy

  • Hysterectomy not indicated

  • Thorough staging:

    • Pelvic and aortic nodes

    • Omentectomy

    • Multiple peritoneal biopsies


Management of ovarian cancer1
Management of Ovarian Cancer

  • Epithelial Ovarian Cancer Stage IC – IV

    • Try to delay chemotherapy until 12-16 weeks of pregnancy

    • Try to delay removal of corpus luteum until 14 weeks

    • First trimester

      • TAB followed by appropriate surgery and chemotherapy

      • Chemotherapy after FNA; C-Section and appropriate management at maturity

    • Second and Third Trimester

      • Chemotherapy first; C-Section and appropriate surgical management at maturity


Malignant germ cell tumors
Malignant Germ Cell Tumors

  • Dysgerminoma (30% of Ovarian malignant neoplasms in pregnancy)

    • Most common GCT

    • Most stage IA

    • Size: avg. 25cm; solid

    • Therapy

      • Surgery: USO, wedge biopsy of opp. Ovary (25% are bilateral), surgically stage.

      • Stage IA & IB: No further treatment

      • Advance stages

        • Hysterectomy not required

        • Chemotherapy


Malignant germ cell tumors1
Malignant Germ Cell Tumors

  • Endodermal sinus tumor

  • Grade 2-3 malignant teratoma

  • Choriocarcinoma (non-gestational)

  • USO and staging for early disease

  • All require chemotherapy regardless of stage


Tumor like ovarian lesions associated with pregnancy
Tumor like Ovarian Lesions Associated with Pregnancy

  • All resolve spontaneously after delivery

  • Conservative surgical approach: frozen section +/- oophorectomy

    • Luteoma of pregnancy - usually an incid. finding at C-Section

      • Micro. -20cm – multiple nodules

      • Bilateral: 1/3 of cases

      • 25% have inc. testosterone

      • Maternal masc. – later ½ of pregnancy

      • Fetal virilization – 70% of female infants

    • Hyperreactio Luteinalis - Bilateral multicystic theca lutein cysts

    • Large solitary luteinized follicular cyst of pregnancy

    • Hilar Cell Hyperplasia – masculinized fetus

    • Intrafollicular Granulosa cell proliferations

    • Ectopic Decidua


Breast cancer in pregnancy 2nd most common cancer in pregnancy
Breast Cancer in Pregnancy (2nd most common cancer in pregnancy)

  • 20% of cases are in women <40 years old

  • 1-2% of cases are pregnant at time of diagnosis

  • One case/1500-3000 pregnancies

  • Often difficult to diagnose

  • Low dose mammogram with appropriate shielding of fetus is “safe”

  • MRI – probably best

  • Diagnosis often delayed

  • Increase incid. of positive nodes (80%)

  • Termination of pregnancy & proph castration is not beneficial

  • No adverse effects on prognosis from subsequent pregnancies


Treatment of breast cancer
Treatment of Breast Cancer

  • Treatment same as non-pregnant

  • Lumpectomy

  • Sentinal node biopsy

    • 2.5mCi technetium 99 – 4.3 mGy at worst. Usually contraindicated.

    • +- radiation

    • Chemotherapy

  • Modified radical mastectomy and nodes

  • Adjuvant chemotherapy after 16 weeks

    • CAF better than CMF in 1st trimester

  • Axillary or localized chest wall RXT is probably safe after the first trimester but can be difficult to shield fetus.

  • Prognosis:


Leukemia in pregnancy
Leukemia in Pregnancy

  • Most abort spontaneously

  • Average age is 28

  • Usually recommend termination of pregnancy because of aggressive chemotherapy

  • Prognosis – dependant on cell type


Hodgkins disease lymphoma in pregnancy
Hodgkins Disease/Lymphoma in Pregnancy

  • Gestational Age

    • <20 weeks: TAB

    • >20 weeks: XRT

      • Chest mantle first

      • Abdominal XRT after delivery

      • 80% curable – depending on cell type


Melanoma in pregnancy
Melanoma in Pregnancy

  • Incidence rising

  • 50% occur in women of child bearing age

  • 9% of cases occur in pregnancy

  • Extremities most common site

  • Pregnancy does not affect prognosis


Ovarian function and chemotherapy
Ovarian Function and Chemotherapy

  • Dose and age related

    • Younger than 25: permanent amenorrhea uncommon

    • Older than 40: 50% permanent ovarian failure

  • OCP’s may prevent ovarian failure

  • Risk of birth defects in offspring not increased (4%)

  • Wait 2-3 years after therapy to become preg – allow for possible recurrent disease


Ovarian function and fertility and radiation therapy
Ovarian Function and Fertility and Radiation Therapy

  • Age and dose related (<20 y.o. – better)

    • Ovaries outside radiation field (avg. dose 54 cGy): No failure

    • Ovaries at edge of radiation field (avg. dose 290 cGy): 25% failure

      • Start to lose function at 150 cGy

    • Ovaries in radiation field: at 500 cGy most women are amenorrheic

  • Oophoropexy to the iliac fossa (use clips to identify ovaries)


Metastases to fetus placenta
Metastases to Fetus/Placenta

  • Only 50 cases in literature

  • Melanoma (50% of reported cases)

  • Leukemia: 1/100 affected pregnancies

  • Lymphoma

  • Breast


Reference list
Reference List

  • Barber H.R.K., Brunschwig A: Am. J. OB/GYN, 85.156, 1963.

  • Baltzer J., Regenfrecht M., Kopche W., Carcinoma of the Cervix and Pregnancy Int. J. Gyneco Obstet. 31:317, 1990.

  • Zemlickis D., Lishner M. Degendorfer P.et.el. Maternal and fetal outcome after breast cancer pregnancy. Am.J. Obstet. Gynecol. 9: 1956, 1991.

  • Karlen J.R. et.al. Dysgermenoma associated with pregnancy. OB/GYN 53:330, 1979.

  • P.Struyk, P.S. Ovarian Masses in Pregnancy Acta.Scand. 63: 421, 1984.

  • Aviles, A. et.al. Growth and Development of Children of Mothers Treated with Chemotherapy during pregnancy: Current status of 43 children. Am. J. Hematology 36: 243, 1991.

  • Brodsky et.al. Am. J. Obstet, Gynecol. 138:1165, 1980.


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