1. Genital cancers and pregnancy Assoc. Prof. Gazi YILDIRIM

2. Incidence by Age of the More Common Malignancies Seen in Pregnancy American Cancer Society, Facts and Figures, 1995

3. Incidence of Tumor Types in Pregnant Women Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N; ESMO Guidelines Working Group. Ann Oncol. 2010 May;21 Suppl 5:v266-73.

4. Cancer in pregnancy The incidence of cancer in pregnancy is approx 1 in 1000. The most common malignancy diagnosed during pregnancy is cervical cancer. (1 in 750)

5. Cancer in pregnancy Cervical cancer (26 %) Breast cancer (26 %) Leukemias (15 %) Lymphomas (10 %) Malignant melanomas (8%)

6. Cervical Cancer in Pregnancy Work-up MRI of pelvis/abdomen Chest X-ray Carcinoembryonic Antigen (CEA) CBC, BUN, Creatine, LFT’s Advanced disease Urine cytology/ cystoscopy Stool for occult blood/ sigmoidoscopy

7. Cervical Cancer in Pregnancy: Treatment by Stage Stage IA1 - <3mm invasion; < 7mm wide 1.2% positive nodes Cone biopsy: no further treatment necessary Vaginal delivery at term Simple hysterectomy post-partum or Cesarian hysterectomy at term

8. Cervical Cancer in Pregnancy: Treatment by Stage Stage IA2 (3-5mm invasion, no vascular inv.): 6.3% positive nodes Stage IB – Disease confined to cervix Stage IIA – vaginal extension Vaginal delivery: increased risk of hemorrhage and cervical laceration Depends on desire for pregnancy First trimester: delay of up to 28 weeks – degree of risk 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

9. Cervical Cancer in Pregnancy: Treatment by Stage Stage IA2, IB, IIA Second trimester: delay of up to 22 weeks Depends on desire for pregnancy Can probably safely wait until maturity Third trimester: delay of up to 10 weeks C-section, Radical hysterectomy and pelvic Lymph node dissection at maturity

10. 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. & pelvic LND if small residual cervical disease Wanted Consider chemotherapy until maturity at 34 weeks

11. 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 Spontaneous abortion at 35 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

12. Ovarian masses Incidental finding in pregnancy is common (1-4%) Majority are functional or CL cysts and spontaneously resolve by 16 weeks gestation Unilateral Noncomplex90% functional Less than 5 cmresolve spontaneously Noticed in 1 st trim

13. Ovarian masses Three main reasons for advising surgery for an adnexal mass in pregnancy are; Risk of rupture Risk of torsion Risk of malignancy

14. Torsion of adnexa The most common time for occurrence is between 6 and 14 weeks and in the immediate puerperium. Commonly associated with a cystic neoplasm Symptoms are usually sudden onset abdominal pain and tenderness Right ovary is involved more frequently than left ovary Benign cystic teratomas and cystadenomas are most common..

15. Ovarian Masses in Pregancy Overall incidence 1:500 pregnancies Increased incidence secondary to sonography Incidence of true neoplasms 1:1,000 pregancies Incidence of ovarian cancer 1:10,000 – 1:25,000 pregancies Unexpected adnexal mass at C-Section 1:700 pregnancies

16. 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%)

17. Management of Ovarian Masses in Pregnancy Generalizations Symptoms Ultrasound/ 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 Ultrasound or MRI, < 6 cm, that do not change over time, do not require surgery Cysts greater than 6-8 cm or inc. in size: “usually” operated on Cysts which persist after 18th week are “usually” operated on Usually operate at 18 weeks to minimize fetal loss

18. Complications of Ovarian Masses in Pregnancy: 10% Total Severe pain: 25% Obstruction of labor: 15% – C-Section Torsion: 10% of cases Sudden pain, Nausea & Vomiting etc. Most common at: 8-16 week – rapid uterine growth (60%) Postpartum – involution (40%) Hemorrhage: 10% of cases Ruptured corpus luteum Germ cell tumor

19. 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

20. Work-up of Ovarian Cancer Pelvic ultrasound MRI pelvis/ abdomen Chest X-ray CA-125: elevated in normal pregnancy, should normalize after 12 weeks AFP, B-HCG, LDH – predominantly solid mass Liver FunctionTests, BUN, Creatinine GI studies only if clinically indicated

21. 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/ aortic node disection/ Omentectomy/ peritoneal biopsies

22. 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

23. Malignant Germ Cell Tumors Dysgerminoma 30% of Ovarian malignant neoplasms in pregnancy Most stage IA Average 25cm; solid Therapy Surgery: USO, wedge biopsy of opposite ovary, surgically stage 25% are bilateral Stage IA & IB: No further treatment Advance stages Hysterectomy not required Chemotherapy

24. 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

25. Tumor like Ovarian Lesions Associated with Pregnancy All resolve spontaneously after delivery Conservative surgical approach: frozen section +/- oophorectomy Luteoma of pregnancy - usually an incident. finding at C-Section Microscopic. -20cm – multiple nodules Bilateral: 1/3 of cases 25% have increased. testosterone Maternal masculinization. – 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

26. 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 incidence of positive nodes (80%) Termination of pregnancy & proph. castration is not beneficial No adverse effects on prognosis from subsequent pregnancies

27. 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: 5 Yr Disease Free Survival Stage I85% Stage II60% Stage II40% Stage IV5%

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

29. Gestational Age and Effects of Antineoplastic Therapy Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N; ESMO Guidelines Working Group. Ann Oncol. 2010 May;21 Suppl 5:v266-73.