Management of Gestational

Choriocarcinoma

Presented by Dr Omoregie O.B.

 management
Introduction
History
Clinical examination
Laboratory investigations
Therapy
- Medical treatment
- Surgical treatment
- Radiotherapy
- Follow-up
 Introduction
Gestational choriocarcinoma is an extreme of a
spectrum of diseases known as trophoblastic
neoplasms
It is a life-threatening condition
GTD elaborate a unique tumour marker HCG –
used for diagnosis and monitoring of Rx
Virtually all patients are now potentially curable
with chemotherapy, especially if correctly
diagnosed and appropriate chemotherapy
commenced early in the course of the disease.
 History
Exaggerated pregnancy symptoms
-hyperemesis
Hydatidiform mole usually presents with
vaginal bleeding at about 12 weeks GA
Passage of vesicles
Recent miscarriage, ectopic gestation or a
term delivery
USS diagnosis – snow storm appearance
 Clinical examination
Height and weight required for surface area
normogram
Early onset pre-eclampsia.
Disproportionate uterine size – greater or less
than date.
Multiple theca lutein cyst – causing ovarian
enlargement may be present.
Hyperthyroidism may be present due to excess
production of thyrotropin by molar tissues
 Investigations
FBC (Hb, WBC, Platelet, prothrombin time, PTT,
fibrinogen).
Serum electrolyte, urea and creatinine.
Liver function test.
Urinalysis
Blood group and crossing matching.
HIV screening
TSH/T4
Pregnancy test (hCG assay)
USS/vaginal colour doppler flow USS
 Principal Investigations
Before commencement of treatment
Assessment of the primary tumour size in
the uterus by clinical examination and
USS
Chest X-ray
Liver span
Lumbar puncture for C.S.F. measurement
of hCG.
CT/MRI – scan brain/liver
Diagnosis of choriocarcinoma
Biochemical (mainly) an elevated β-hCG plateau
or rising hCG titre over a period of several
weeks
Histology – absent villi structure, sheets or foci
of trophoblasts on an haemorrhagic or necrotic
tissue background, marked nuclear atypia (the
entire specimen must be processed for
histologic study, when curettage is done, since
only a small foci of isolated area of
choriocarcinoma may be present).
 Pregnancy test
HCG, LH, FSH, TSH have a common α-subunit,
but the biological specificity is conferred by β-
subunit, by raising an antisera to the β-subunit of
HCG, the cross reactivity with other glycoprotein
hormones is reduced.
A good β-HCG assay can detect values greater
than 2miu/ml in normal serum.
HCG can also be monitored using urine, but has
lots of interference, hence monitoring using
serum is preferable especially in patients on
therapy.
 Hydatidiform mole follow-up
The commonest antecedent pregnancy to
choriocarcinoma is HM
Using HCG measurement to determine if the
mole is regressing spontaneously or actively
growing.
The amount of HCG found in the serum or
excreted urine correlates closely with the
number of viable tumour cells present.
Approximately 90% of patient with HM have
spontaneous regression, but 10% would require
chemotherapy
 Rx of Hydatidiform mole
Suction curettage is Prostaglandin
advocated (largest induction, oxytocin
curette possible), induction or intra-
followed by a gentle amniotic instillation of
sharp curettage. prostaglandin or
i.v oxytocin should be hypertonic solutions
started after removing (saline, glucose, urea
a moderate amount of etc) are not
tissue, and may acceptable methods
continue for 24hrs if for evacuation –
necessary increase need for
chemotherapy
Surveillance post-evacuation of HM
Weekly β-hCG assay post-
evacuation, until it
becomes undetectedable
on 3 consecutive assays
If hCG titre remission
occurs spontaneously
within 14wks without a titre
plateau, the hCG assay
thereafter is done 4 weekly
for at least 1 year before
patient is discharge from
surveillance.
Partial mole – 6-12 months
Contraception – oral contraceptive.
Gynaecologic examination started 1
week post evacuation – assess Ut
size, adnexal masses, check for
metastases on the vulva, vagina,
urethra, and cervix. If no
complication repeat exam 4 wkly
throughout period of surveillance.
CXR repeated every 4wks for those
that had pulmonary metastasis prior
to evacuation, until remission,
thereafter every 3 months for period
of surveillance.
Pregnancy – allowed after 1yr of
been negative during surveillance.
Indications for chemotherapy
A high level of hCG more than 4 weeks after
evacuation (serum level >20,000iu/l or urine
level >30,000iu/l)
Progressively rising hCG levels at any time after
evacuation.
Histological diagnosis of choriocarcinoma at any
site, or evidence of CNS, renal, hepatic,
gastrointestinal metastases or pulmonary
metastases >2cm in diameter or > 3 in number.
Persistent uterine bleeding and positive hCG
levels
 Prognostic assessment
The principal investigations are for
prognostic categorisation.

(FIGO 2002 cancer committee)

Low risk (0-6)
High risk (>7)
 Treatment
Patients should be managed in a specialist
unit.

Chemotherapy
Surgery
Radiotherapy
Pelvic artery (hypogastric A) embolization
 Chemotherapy Regimen
Non-metastatic Choriocarcinoma
Single agent chemotherapy:
Methotrexate 0.4mg/kg IM for 5 days repeated
every 2 wks (ass 10% primary failure rate).
Methotrexate 1.0mg/kg IM every other day for 4
doses (day 1,3,5 and 7) with folinic acid
(leucovorin) 0.1mg/kg IM every 24hrs after each
dose of methotrexate (ass 20-25% primary failure
rate).
Methotrexate 50mg/m2 IM given wkly. this regimen
has 30% primary failure rate.
Chemotherapy contd.
(d) Actinomycin-D, 1.25mg/m2 IV given every 2 wks. (Ass 20%
primary failure rate).
(e) Actinomycin-D, 12mcg/kg IV daily for 5 days, repeated
every 2wks (it may be used for patient with hepatic
dysfunction) it has 8% primary failure rate.
(f) Methotrexate 250mg infusion over 12hrs. This is the MTX
portion of the EMA-CO protocol. It is associated with a
30% primary failure rate.

Note: Actinomycin-D causes severe slough if infiltrated into the

skin, therefore ensure inject via a new free running
intravenous infusion. If extravasation occurs infiltrate the
area with 100mg hydrocortisone and 2 cc of 1% xylocaine.

Repeat FBC, platelet, E/U/Cr, LFT should be done before

commencement of next course of Rx.
 Chemotherapy contd.
Metastatic choriocarcinoma.
Combination chemotherapy
First line drugs:
EMA-CO regimen – Etoposide,
methotrexate with leucovorin rescue and
actinomycin-D given on days 1 and 2, then
cyclophosphamide and vincristine
(oncovin) are given on day 8.
Chemotherapy contd.
EMA-CO is more acceptable and far less
toxic than MAC chemotherapy.
MAC (methotrexate, Actinomycin, and
Cytoxan; originally C was chlorambucil).
However, several centres are returning to
use of MAC due to risk of leukaemia with
EMA-CO (used for more than 6 courses).

Course of EMA-CO are repeated sequentially until remission is

obtained. Neupogen is usually given to sustain white cells.
Chemotherapy “for the road”
Following the 1st non-detectable β-hCG, at least
3 further courses of chemotherapy should be
administered, with the 1st course being
combination chemotherapy.

A negative hCG value implies that the number of

malignant trophoblastic cells present in the body
is less than 107. it does not mean that the
disease at that time is completely eradicated.
 Brain metastasis
Increase the methotrexate dose in EMA-CO
protocol to 1g/m2, the urine should be alkalinized
with iv bicarbonate
Depending on tumour size there might be need
for irradiation of whole brain or excisional
surgery.
The irradiation is to prevent catastrophic
haemorrhage rather than controlling the
trophoblastic disease.
Irradiation may also be needed for liver
metastasis.
 Resistance to EMA-CO
Or recurring after previous multiagent
chemotherapy.
Rx with EMA-EP protocol, i.e EMA alternating
with etoposide and platinum.
OR
EMA alternating with cis-platinum and
adriamycin – EMA-PA.
For EMA-EP resistant cases Taxol with cisplatin
alternating with Taxol-etoposide or Taxol-5FU or
iphosphamide, cisplatinium, etoposide (ICE) or
vinblastine, etoposide, cisplatin (BEP)
Radiotherapy: used concomitantly with
combined chemotherapy in patients with
liver or brain metastasis.
Cerebral metastasis Rx over 2 wks with
300 rads daily, 5 days a week, to a total
organ dose of 3000 rads.
Whole liver irradiation Rx over 10 days
with 200 rads daily, 5 days a week, to a
total organ dose of 2000 rads

Pelvic artery embolization is used in cases

of intractable haemorrhage.
Surgery for chemotherapy resistant
and persistent metastases.
Lung, liver, brain, or other sites
metastases that do not regress with
chemotherapy may be amenable to
surgical extirpation.
 Prophylactic chemotherapy
The concensus is that, it is only now
recommended for those likely to default
follow-up
Pregnancy after chemotherapy
Patients need to wait for 12 months after
chemotherapy before undertaking further
pregnancy.
 CONCLUSION
It should be noted that choriocarcinoma
remains an enigma in gynaecological
practice.
It stretches both the patient and the
managing physician to the limit.
There is the need to continuously audit its
management in our environment, so as to
improve management outcome.