1. Gestational Trophoblastic Disease
Dr U.D.Bafna MD
Professor & Head, Department of Gynecologic Oncology,
Kidwai Memorial Institute of Oncology,
Bangalore

2. Gestational Trophoblastic Disease (GTD)
GTD :Refers to benign and malignant trophoblastic diseases –
Hydatidiform mole
Invasive mole
Choriocarcinoma (CCA)
and Placental site trophoblastic tumor (PSTT)

3. Gestational Trophobastic tumor or neoplasia – GTT/GTN
GTN (GTT) : Refers to clinical/biochemical evidence of
IM,
CCA &
PSTT
These patients require chemotherapy (&/ or excisional surgery)

4. GTN
GTN is seen in some patients following evacuation of molar pregnancy (about 80% regress normally and 20 % develop GTN)
GTN may also rarely follow an abortion and very rarely a term delivery (1 in 100,000 term deliveries).

5. Diagnosis of GTN
Following H. mole is fairly easy due to meticulous follow up and high degree of suspicion
Its difficult to diagnose after an abortion or term delivery as the symptoms are non-specific. Patients may present with non-gynec symptoms like haemoptysis due to lung metastasis.

6. Risk of progression to GTN following molar pregnancy
Hydatidiform Mole (20% over all)
Partial Complete
Low Risk High Risk
4% % %
GTN GTN GTN

7. Gestational Trophoblastic Disease
Hydatidiform Mole
Low Risk (4%) High Risk (40%)
Uterine size > period of gestation
ShCG > 100,00 miu/ml
Large Theca-Lutein cysts ( > 6 cm)
PIH, thyrotoxicosis, pulmonary
embolism, Previous mole
(all these indicate high trophoblastic proliferation)

8. Genetic basis of molar pregnacy
Partial Mole – diandric triploid (69) usually
46 maternal chromosomes and 23 paternal chromosomes
Maternal chromosomes are responsible for proper development of embryo and paternal chromosomes for placental development
Complete Mole – diandric diploid (46 chromosomes)
Here all the 46 chromosomes are of paternal origin and therefore there is only trophoblastic proliferation and no development of embryo

9. Molar pregnancy Incidence – 1 in 1000 (west) to 1 in 400 (Asia)
More common if maternal age is > 35 or <20 years
Chances of repeat mole is 2%
Chances increase to 20% after two molar pregnancies

10. Molar pregnancy
Signs and symptoms are due to excessive trophoblastic proliferation – resulting in
Increased uterus size,
Excessive nausea and vomiting
PIH
Hyperthyroidism
Early vaginal bleed
Passage of grape like cysts
Diagnosis is easy by ultrasound and serum hcg

11. Evacaution of a mole Suction evacuation
Some patients may develop trophoblastic embolisation causing respiratory distress
There is no role of repeat curettage after a week unless there is residual mole
Medical Induction is contraindicated because of increased risk of embolisation

12. Management after evacuation of the Mole
Meticulous follow up with serial B hCG estimation to detect persistent trophoblastic disease in the form of GTN is essential

13. Follow up with serum B hCG
Serum B hcg should be measured weekly
for three times till normal and then monthly
at least for one to two years after molar
pregnancy

14. hCG Human chorionic gonadotrophin (hCG): it is a glycoprotein
produced by syncytiotrophoblasts. It contains a and b subunits
joined by non-covalent bonds.
In normal pregnancy, most hCG is intact.
In GTD, there is a higher proportion of b-hCG compared with that in normal pregnancy.
b-hCG not only reflects trophoblastic activity but also promotes tumourigenesis.

15. hCG
Various forms of b-hCG exist in GTD, including free-b, b-core, nicked free-b and carboxyl-terminal fragment.
Therefore, an ideal hCG assay for GTD should detect all forms of b-hCG.
False-positive and false negative results can occur.
Phantom hCG (pseudohypergonadotropinemia ) is a result of the presence of heterophilic antibodies in serum giving rise to a falsely elevated hCG..
The alternative is to measure the urine hCG level because heterophilic antibodies are not excreted into the urine.

16. Management after evacuation of mole
Prophylactic Chemotherapy
Single agent , single eight day courseof methotrexate with folinic acid rescue may be given to a patient who is unreliable for follow up following molar pregnancy – especially if it is high risk (excess trophoblastic proliferation)

17. Prophylactic Hysterectomy
With or with out prophylactic
chemothrapy may be done for unreliable
multi-parous patient aged > 39 years.
This is to decrease the risk of development of
perforating invasive mole

18. Contraception after molar
Barrier/IUCD/Oral Pills
Contraception for a minimum period of six
months after B hcg has become normal

19. Future Conceptions after Molar
Repeat molar pregnancy – 3%,
20-30% after two consecutive molar pregnancy
After three consecutive molar pregnancy normal
pregnancy is very rare
Early USG during the subsequent conceptions

20. Gestational Trophoblastic Neoplasia (GTN)
Includes IM, CCA and PSTT
1)Invasive Mole : HM that has invaded
the myometrium or metastasised
2)Choriocarcinoma: differs from IM in that
the villous pattern is lost
3)Placental Site Trophoblastic Tumor

21. Note – all metastatic disease need not be chorioca, it could also be an invasive mole which responds better to chemotherapy.
There is no need for histo-patholgy/biopsy as serum b–hcg is a very sensitive and specific marker

22. Gestational Trophoblastic Neoplasia (GTN)
3)Placental Site Trophoblastic Tumor
- composed mainly of cytotrophoblasts
- hPL is raised > hCG
- less responsive to chemotherapy
- Follows either a molar pregnancy (50% of cases of PSTT), abortion (25%), term pregnancy (20%), or ectopic (5%)

23. GTN - Diagnosis May arise after HM, Abortion or Term delivery
High degree of suspicion is required after abortion or term delivery as symptoms may be highly non-specific/non-gyn symptoms depending on the site of metastasis
Any young woman with metastasis of unknown origin should be screened for GTN

24. GTN - Diagnosis Diagnosis after HM evacuation : FIGO
Recommendations (2000)
1)4 values or more of plateau of hCG over at
least 3 weeks
2)A rise of hCG of 10% or greater for 3
values over at least 2 weeks
3)The presence of histologic choriocarcinoma
4)Persistence of hCG 6 months after evacuation
A single value of high b hcg of 20,000 miu/ml at 4 weeks after evacuation

25. Mangement of GTN
GTN is mainly managed with chemotherapy as the tumor is highly sensitive to chemotherapy (except PSTT)
(God’s first cancer and man’s first cure)
Chemotherapy is either single agent or combination chemotherapy depending on the FIGO stage and/or WHO risk score

26. FIGO stage Stage I – confined to uterus
Stage II – extension to pelvis and vagina
Stage III – Lung metastasis
Stage IV – all other mets

27. GTN – WHO Score The Scoring System for FIGO 2000 Score 1 2 4 Age1 2 4
Age
<39
>39
A.P HM
Abortion
Term
Interval
<4 m
4-6
7-12
hCG IU/ml
< 1
1-10
10-100
>100
Tumor Size (CM)
3-4 5
Site
Spleen
Kidney
GIT
Brain
Liver
No.
1-4
4-8
>8
Previous failed CT
Single drug
Two or more

28. GTN FIGO 2000 Score Low Risk GTN : Score 6 or less
High Risk GTN : Score >6

29. Requirements for Scoring and Diagnosis of Metastases:
Clinical History & Serum hCG estimation
Chest X-ray/CT scan for diagnosis of lung metastases
USG/CT scan for diagnosis of intra-abdominal metastases
MRI/CT scan for Brain metastases
* All the patients with lung metastases should have CT/MRI of brain

30. Management of GTN General Principles
GTN is highly curable even in very advanced stages as it is highly chemosensitive
Chemotherapy should be used in proper combination, proper schedule, proper
dosage – otherwise tumor may become chemo-resistant very rapidly

31. Role of surgery for GTN
Surgery is generally not required as the tumor is chemosensitive
However, surgery may be done to decrease the tumor load and reduce the number of chemotherapy cycles in selected patients
Example – hysterectomy in a multiparous women with large uterine tumor and high risk who score

32. Role of surgery
Surgery is also indicated for removal of chemoresistant tumor any where in the body
Example – Hysterectomy,
Pulmonary lobectomy
Craniotomy
Surgery is done generally for a solitary chemoresistant tumor which can be excised completely

33. Management of GTN General Principles
Low Risk GTN is mostly cured with single agent chemotherapy
High Risk GTN should be always treated with combination chemotherapy

34. Low Risk GTN- Chemotherapy
Inj. Methotrexate 1 mg/kg on D 1,3,5 & 7
Inj. Leucovorin 0.1 mg/kg oRn D 2,4,6 & 8
Repeat cycle on D 15 ( if no toxicity).
Estimate serum hCG serially weekly.
Continue CT for 1-2 cycles after normalization of hCG.
Change CT if hCG values plateau or rise

35. Low Risk GTN- Chemotherapy
Kidwai Data ( Bafna et al , Int J Gyncol Ca, 1997)
100% remission
78.7% achieved remission with single agent MTX
21.3% with comination CT or Actinomycin D

36. High Risk GTN - Chemotherapy
EMA-CO REGIMEN
EMA on D 1 & 2, CO on D8
Repeat cycle on D 15 ( if no toxicity).
Estimate serum hCG serially weekly.
Continue CT for 3-4 cycles after normalization of hCG.
Change CT if hCG values plateau or rise/
Consider excisional surgery for localized tumor

37. High Risk GTN Kidwai Data (Bafna et al., 1997) 83.7 % remission
Site of metastases in this series included - Pelvis, lung, liver,brain, GIT, Spine, Parotid
Clinical presentation included Gyn symptoms, hemoptysis, hemiplegia, paraplegia, facial nerve palsy etc.

38. High Risk GTN Kidwai Data (Bafna et al., 1997) 83.7 % remission
56.7% achieved remission with first line chemotherapy*
27% achieved remission with second and third line CT
* This series also includes patients before the advent of EMA_CO regimen.

39. Follow up after GTN treatment
Meticulous follow up with serial hCG estimation
Contraception for a period of one year after remission has been achieved
No evidence of increased obstetric complications during subsequent normal conceptions.

40. Contraception for one year as most of the recurrences occur within one year
One year period may also be required to allow recovery of primordial follicles damaged by chemotherapy
Chemotherapy is known to suppress ovarian function and cause amenorrhea for a short period.

41. Have a great & wonderful day
Thank You
Have a great & wonderful day
Department of Gynaec Oncology

43. High Risk GTN - Chemotherapy
Supportive therapy is important in patients with extensive brain/lung metastases –
Steroids to decrease brain/lung
edema
Positive pressure ventilation
Hemostatic radiotherapy to brain