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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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