Diagnosis, classification and treatment of gestational trophoblastic neoplasia

Biscaro, Andressa; Braga, Antônio; Berkowitz, Ross Stuart

doi:10.1590/SO100-720320140005198

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Review • Rev. Bras. Ginecol. Obstet. 37 (1) • Jan 2015 • https://doi.org/10.1590/SO100-720320140005198 linkcopy

Diagnosis, classification and treatment of gestational trophoblastic neoplasia

Diagnóstico, classificação e tratamento da neoplasia trofoblástica gestacional

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Gestational trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.

GTN: FIGO staging and classification (Washington, 2000)
FIGO anatomic staging:
Stage I: Disease confined to the uterus
Stage II: GTN extends outside of the uterus, but is limited to the genital structures (adnexa, vagina, broad ligament)
Stage III: GTN extends to the lungs, with or without known genital tract involvement
Stage IV: All other metastatic sites
Modified WHO prognostic scoring system as adapted by FIGO
Prognostic factors	Score
Prognostic factors	0	1	2	4
Age	<40	≥40	–	–
Antecedent gestation	mole	abortion	term	–
Interval (months)	<4	4–6	7–12	>12
Pretreatment serum hCG (mIU/mL)	<10³	10³ to <10⁴	10⁴ to <10⁵	>10⁵
Largest tumor size (including uterus)	<3	3 to 4	≥5	–
Site of metastases	lung	spleen, kidney	GIT	brain, liver
Number of metastases	–	1–4	5–8	>8
Previous failed chemotherapy	–	–	single drug	≥2

ChT regimen	Primary remission rate (%)
1) MTX 0.4 mg/kg (maximum 25 mg) IV or IM qd for 5 days, repeat every 14 days	87–93
2) MTX 30-50 mg/m² IM weekly	49–74
3) MTX 1 mg/kg IM d 1, 3, 5, 7; folinic acid 0.1 mg/kg IM d 2, 4, 6, 8; repeat every 15-18 d, or as needed	74–90
4) MTX 100 mg/m2 IVP, then 200 mg/m² in 500 mL D5W over 12 h; folinic acid 15 mg IM or PO every 12 h for 4 doses beginning 24 h after start of MTX; repeat every 18 d, or as needed	69–90
5) Act-D 10-13 mg/kg IV qd for 5 d; repeat every 14 d	77–94
6) Act-D 1.25 mg/m2 IV every 2 weeks	69–90
7) Alternating MTX/Act-D regimens 1 and 5	100

EMA-CO and EMA-EP protocols
Day	Drug	Dose
EMA-CO
1	Etoposide ActD MTX	100 mg/m² by infusion in 200 mL saline over 30 min 0.5 mg IVP 100 mg/m² IVP 200 mg/m²by infusion over 12 h
2	Etoposide ActD Folinic acid	100 mg/m² by infusion in 200 mL saline over 30 min 0,5 mg IVP 15 mg IM or PO every 12 h for 4 doses starting 24 hours after start of MTX
8	Cyclophosphamide Vincristine	600 mg/m² by infusion in saline over 30 min 1 mg/m² IVP
EMA-EP
1	Etoposide ActD MTX	100 mg/m² by infusion in 200 mL saline over 30 min 0.5 mg/m² IVP 100 mg/m² IVP 200 mg/m²by infusion over 12 h
2	Etoposide ActD Folinic acid	100 mg/m² by infusion in 200 mL saline over 30 min 0.5 mg/m² IVP 15 mg IM or PO every 12 h for 4 doses starting 24 hours after start of MTX
8	Cisplatin Etoposide	60 mg/m² IV with prehydration 100 mg/m²by infusion in 200 mL saline over 30 min

Chemotherapy regimens
EMA-EP: Etoposide, Methotrexate, Actinomycin-D, Etoposide, Cisplatin
BEP: Bleomycin, Etoposide, Cisplatin
TP/TE: Paclitaxel, Cisplatin/Paclitaxel, Etoposide
FA: 5-Fluorouracil, Actinomycin-D
FAEV: Floxuridine, Actinomycin-D, Etoposide, Vincristine
MBE: Methotrexate, Bleomycin, Etoposide
VIP/ICE: Ifosfamide, Cisplatin, Etoposide

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Interval (in months) between the end of antecedent gestation (when known) and symptom onset; FIGO: International Federation of Gynecology and Obstetrics; WHO: World Health Organization; GTN: gestational trophoblastic neoplasia.