1. Gestational Trophoblastic Disease Max Brinsmead MB BS PhD March 2015

2. Gestational Trophoblastic Disease (GTD) is… A spectrum of disorders in which trophoblastic tissue (usually of pregnancy origin) proliferates abnormally The spectrum includes:  Hydatidiform mole Complete and Partial  Invasive mole  Placental site trophoblastic tumour  Choriocarcinoma Persisting or recurrent disease is better termed Gestational Trophoblastic Neoplasia or GTN

3. Gestational Trophoblastic Neoplasia (GTN) is remarkable because… There are marked geographical and ethnic differences in its incidence that have  A presumed genetic and  Possibly environmental origins There are identified chromosomal abnormalities Has a tumour marker (beta HCG) that is…  highly sensitive and  100% specific (normal pregnancy excluded) Has very high rates of response to chemotherapy

4. Molar Pregnancies Complete Mole Diploid chromosomes No fetal tissue present Androgenic (paternal) in origin  75% arise from duplication of a monospermic fertilization  25% arise from dispermic fertilization of an “empty ovum” Partial Mole  90% are triploid and 10% tetraploid or mosaic  Arise when there is dispermic fertilization of a “normal ovum”  Usually have a fetus or some fetal tissue Chromosome studies and P57 immunochemical histology helps to distinguish the two

5. GTD Incidence and Risk of Malignancy Incidence of ≈ 1:750 Caucasian pregnancies ≈ 1:400 Asian pregnancies May be as many as 1:110 pregnancies in SE Asia 10-fold more common when maternal age is >40 years Complete mole has a 15% risk of GTN Partial mole has a 0.5% risk of GTN But only 1:50,000 normal pregnancies go on to GTN

6. Common Presentations of GTD Bleeding in early pregnancy “Large for dates” and no fetus or FH found As an incidental finding during routine early pregnancy ultrasound  Placenta has a “snow-storm” appearance  Partial mole more difficult and may be diagnosed only after histology of failed 1 st trimester pregnancy tissue  Occurs more commonly with twin pregnancies

7. Uncommon Presentations of GTD * Hyperemesis **Early onset pre eclampsia (<20w) Thyrotoxicosis Due to a TSH-effect of abundant HCG Abdominal distension with theca lutein cysts *Secondary postpartum haemorrhage or ongoing PV bleeding after any pregnancy Seizures (from brain metastases) or haemoptysis (from lung metatases)# Acute respiratory failure *Most of these are not GTD #Choriocarcinoma **Classically with triploidy

8. Management of Molar Pregnancies Suction curettage preferred over medical evacuation Because of the risk of trophoblastic embolisation Cervical ripening with PG’s acceptable Oxytocin infusion for life threatening haemorrhage Large fetal parts with a partial mole will require prostaglandins Mole plus a normal twin pregnancy presents dilemmas But the prognosis for the normal twin is very grim But risk of GTN is not increased and there is a normal response to chemotherapy if required Don’t forget the Anti-D if Rh negative

9. Never miss a mole or GTN by… Always send “products of conception” for histology When passed spontaneously When curetted after failed pregnancy After curette for secondary postpartum haemorrhage Not required after termination of pregnancy When there has been a normal ultrasound before TOP Or fetal parts are identified Do a urine test for HCG 3 weeks after all non- surgically managed failed pregnancy And no POC for histology And do a HCG for any abnormal bleeding within 3 months of any pregnancy Or the woman presents with a weird tumour

10. Follow up of molar pregnancies: Monitor for GTN after complete mole by… Weekly HCG until 3 consecutive are negative Or at 8w if negative before Then monthly for 6m No pregnancy please for 6m from time of 1 st negative test For Partial Mole May stop weekly HCG’s when negative No pregnancy for 6m please COC increases the risk of GTN by RR 1.19 Barrier contraceptives best But only until the HCG returns to normal And any contraceptive is better than another pregnancy

11. Management of Gestational Trophoblastic Neoplasia Best done by registering all molar pregnancies with a Specialist Centre Methotrexate is the 1 st line drug but treatment requires individualization And multi-agent chemotherapy may be required Second curette rarely necessary A few patients require surgery as part of their care

12. FIGO 2000 Score for GTN

13. Chemotherapy for GTN is based on FIGO Score.. For score ≤ 6 Methotrexate only: Alternate daily for a week With Folinic acid rescue on the alternate days Then rest for 6 days and measure HCG Repeat as necessary until HCG is normal Then weekly HCG for 6w and monthly for 12m For score ≥ 7 Multi-agent chemotherapy: Dactinomycin Cyclophosphamide Vincristine Etoposide

14. Prognosis after chemotherapy for GTN Cure rates in excess of 97% should be possible Risk of another molar pregnancy is 1:80 No increased obstetric risk Unless the pregnancy is conceived within 12m of chemotherapy Increased risk of pregnancy loss (some by TOP) But no increased risk of fetal malformation Menopause occurs slightly earlier By a mean of 12m or 3 yrs after multi-agent chemo And some women at risk of developing secondary cancers if chemo continued >6m Leukemia (RR 16.6) Ca colon (RR 4.6), melanoma (RR 3.4), Ca breast (RR 5.6)

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