Management Of Choriocarcinoma

Management of Gestational Choriocarcinoma

Presented by Dr Omoregie O.B.

management

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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 βsubunit, 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 advocated (largest curette possible), followed by a gentle sharp curettage. i.v oxytocin should be started after removing a moderate amount of tissue, and may continue for 24hrs if necessary

Prostaglandin induction, oxytocin induction or intraamniotic instillation of prostaglandin or hypertonic solutions (saline, glucose, urea etc) are not acceptable methods for evacuation – increase need for chemotherapy

Surveillance post-evacuation of HM Weekly β-hCG assay postevacuation, 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.