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Cancer in Pregnancy

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

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  1. Cancer in Pregnancy Jeffrey Stern, M.D.

  2. 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!

  3. 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%)

  4. What’s Different About Pregnancy? • Hormones • Metabolic Changes • Hemodynamics • Immunology • Increased vascularity • Age • Few cases – anecdotal experience • Inherent bias – breast cancer, ovarian cancer

  5. 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

  6. 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

  7. 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)

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. False Negative Pap Smear

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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%)

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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:

  39. Leukemia in Pregnancy • Most abort spontaneously • Average age is 28 • Usually recommend termination of pregnancy because of aggressive chemotherapy • Prognosis – dependant on cell type

  40. 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

  41. 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

  42. 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

  43. 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)

  44. Metastases to Fetus/Placenta • Only 50 cases in literature • Melanoma (50% of reported cases) • Leukemia: 1/100 affected pregnancies • Lymphoma • Breast

  45. 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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