Gestational Trophoblastic Disease

1. Gestational Trophoblastic Disease Max Brinsmead PhD FRANZCOG March 2010

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 1st 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 1st 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 pregnancieswith a Specialist Centre • Methotrexate is the 1st 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)