gestational trophoblastic disease dr u.d.bafna md professor & head, department of gynecologic...
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Gestational Trophoblastic Disease
Dr U.D.Bafna MD
Professor & Head, Department of Gynecologic Oncology,
Kidwai Memorial Institute of Oncology,
Bangalore
Gestational Trophoblastic Disease (GTD)
GTD :Refers to benign and malignant trophoblastic diseases – Hydatidiform mole Invasive moleChoriocarcinoma (CCA) and Placental site trophoblastic tumor (PSTT)
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)
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).
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.
Risk of progression to GTN following molar pregnancy
Hydatidiform Mole (20% over all)
Partial Complete
Low Risk High Risk
4% 4% 40%
GTN GTN GTN
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)
Genetic basis of molar pregnacy
Partial Mole – diandric triploid (69) usually46 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
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
Molar pregnancy
Signs and symptoms are due to excessive trophoblastic proliferation – resulting in Increased uterus size, Excessive nausea and vomitingPIHHyperthyroidismEarly vaginal bleedPassage of grape like cysts
Diagnosis is easy by ultrasound and serum hcg
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
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
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
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.
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.
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)
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
Contraception after molar
Barrier/IUCD/Oral PillsContraception for a minimum period of six months after B hcg has become normal
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
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
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
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%)
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
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 evacuationA single value of high b hcg of 20,000 miu/ml at 4 weeks after evacuation
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
Stage I – confined to uterus Stage II – extension to pelvis and vagina Stage III – Lung metastasis Stage IV – all other mets
FIGO stage
GTN – WHO Score The Scoring System for FIGO 2000
Score 0 1 2 4
Age <39 >39
A.P HM Abortion Term
Interval <4 m 4-6 7-12hCG IU/ml
< 1 1-10 10-100
>100
Tumor Size (CM)
3-4 5
Site Spleen
Kidney
GIT Brain
Liver
No. 0 1-4 4-8 >8Previous failed CT
Single drug
Two or more
GTN FIGO 2000 Score
Low Risk GTN : Score 6 or less High Risk GTN : Score >6
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
Management of GTN
General PrinciplesGTN 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
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
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
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
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
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
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
High Risk GTN
Kidwai Data (Bafna et al., 1997)83.7 % remissionSite 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.
High Risk GTN
Kidwai Data (Bafna et al., 1997)83.7 % remission56.7% 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.
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.
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.
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