What is the management approach for gestational trophoblastic disease (GTD)?

Management of Gestational Trophoblastic Disease

Centralize care at a specialized GTD reference center for optimal pathology review and serial hCG monitoring, as this approach maximizes cure rates and minimizes mortality. 1, 2

Initial Evaluation and Diagnosis

Molar Pregnancy Management

• Terminate singleton molar pregnancies by suction dilation and curettage (D&C) as the standard approach 1
• Administer Anti-D prophylaxis following suction D&C of partial hydatidiform mole (PHM) in Rh-negative patients 1
• Avoid repeat D&C for recurrence, as it rarely prevents the need for chemotherapy and should only be attempted after discussion with a GTD reference center 1

Risk Stratification

• Apply the FIGO prognostic scoring system to determine risk of resistance to single-agent chemotherapy 1, 2
• Note that the FIGO score is not valid for placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) 1

Treatment Algorithm Based on FIGO Score

Low-Risk Disease (FIGO Score 0-6)

First-Line Chemotherapy:

• Methotrexate with folinic acid (MTX/FA) is preferred in most European centers due to lower toxicity compared to MTX alone or single-agent actinomycin D (ActD), with cure rates approaching 100% even if first-line therapy fails 1, 2
• Alternative options include single-agent MTX without FA or ActD 1, 2
• Continue chemotherapy for 6 weeks of maintenance treatment after hCG normalization 1, 2

Exception:

• Patients with low-risk scores but hCG levels >400,000 IU/L should receive multi-agent chemotherapy from the outset 2

High-Risk Disease (FIGO Score ≥7)

First-Line Chemotherapy:

• EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) is the standard multi-agent regimen, achieving survival rates of 80-90% 1, 2, 3
• EMA/CO is highly effective, simple to administer, and relatively non-toxic 1
• Continue maintenance therapy for 6 weeks after hCG normalization, extended to 8 weeks for poor prognostic features such as liver with or without brain metastasis 1, 2

Ultra-High-Risk Disease:

• Reduce early deaths with induction of low-dose etoposide and cisplatin before transitioning to standard therapy 1
• Consider substituting EMA/CO with EP/EMA (etoposide/cisplatin alternating with etoposide/methotrexate/actinomycin D) 1

Management of Chemoresistant/Relapsed Disease

Salvage Chemotherapy

• High-risk failures can be salvaged with EP/EMA or TE/TP (paclitaxel/etoposide alternating with paclitaxel/cisplatin) 1
• TE/TP appears better tolerated than EP/EMA based on non-randomized data 1
• Surgery alone can salvage patients with isolated foci of chemoresistant disease 1

Important Considerations

• Residual lung or uterine masses following chemotherapy are not predictive of recurrence and do not require surgical excision 1

Special Entities: PSTT and ETT

Stage I Disease (Presenting Within 4 Years)

• Hysterectomy with pelvic lymph node sampling is recommended for stage I PSTT/ETT presenting within 4 years of the last known pregnancy 1, 2
• Ovarian conservation is appropriate unless there is a family history of ovarian cancer or the patient is post-menopausal 1

Metastatic Disease

• Multi-agent chemotherapy with EP/EMA is recommended for metastatic PSTT/ETT 1, 2
• Continue therapy for 8 weeks after hCG normalization 1
• Unlike choriocarcinoma, residual masses should be removed surgically as they can harbor microscopic disease 1

Disease Presenting Beyond 4 Years

• Patients presenting beyond 4 years may benefit from multi-agent chemotherapy and subsequent high-dose chemotherapy 1
• The interval from last known pregnancy is the most dominant prognostic factor, with 100% mortality for those presenting ≥48 months versus 98% survival for <48 months 1

Critical Pitfalls to Avoid

• Never biopsy visible lesions in the lower genital tract due to severe hemorrhage risk from fragile trophoblastic tumor vessels 2
• Do not use weekly intramuscular methotrexate as it is less effective than 5- or 8-day methotrexate regimens 2
• Consider phantom hCG if hCG is elevated with no evidence of disease on imaging 2
• Monitor for drug resistance early during initial therapy using weekly hCG measurements to detect plateau or rise requiring treatment change 2
• Histological confirmation is essential for PSTT diagnosis, as hCG levels are typically low for the volume of disease present 1