A 28-year-old woman presents with vaginal bleeding and a markedly elevated β-hCG level of 450,000 mIU/mL. Ultrasound shows a molar pregnancy with no fetal parts. After suction evacuation, she develops persistent gestational trophoblastic neoplasia with pulmonary metastases and an FIGO score of 8. What is the drug of choice for this high-risk molar pregnancy?

## First-Line Chemotherapy for High-Risk GTN **Key Point:** High-risk gestational trophoblastic neoplasia (FIGO score ≥7, or any GTN with metastases and/or high β-hCG) requires combination chemotherapy, NOT single-agent methotrexate. ### FIGO Risk Stratification | Feature | Points | |---------|--------| | Age > 40 years | 1 | | Antecedent abortion | 1 | | Interval from index pregnancy > 4 months | 2 | | β-hCG > 100,000 mIU/mL | 4 | | ABO blood group (O vs AB) | 1 | | Largest tumor > 3 cm | 2 | | Site of metastasis (lung/vagina vs other) | 0/1/4 | | Number of metastases (1–4 vs > 4) | 1/2 | | Prior failed chemotherapy | 4 | **Score ≥7 = High-risk; <7 = Low-risk** ### Treatment Algorithm ```mermaid flowchart TD A[GTN diagnosed]:::outcome --> B{FIGO score?}:::decision B -->|< 7 Low-risk| C[Single-agent methotrexate]:::action C --> D[Intramuscular or IV dosing]:::action B -->|≥ 7 High-risk| E[Combination chemotherapy]:::action E --> F[EMA regimen preferred]:::action F --> G[Etoposide 100 mg/m² IV daily × 5]:::action G --> H[Methotrexate 1 g/m² IV + folinic acid rescue]:::action H --> I[Actinomycin D 0.5 mg IV daily × 5]:::action I --> J[Repeat every 14 days]:::action J --> K{β-hCG normalized?}:::decision K -->|Yes| L[Continue 1–2 more cycles post-normalization]:::action K -->|No| M[Escalate to MAC or other regimen]:::action ``` **High-Yield:** EMA (etoposide, methotrexate, actinomycin D) is the preferred first-line combination for high-risk GTN because it has superior cure rates (>90%) compared to older regimens, with manageable toxicity. This patient's FIGO score of 8 (β-hCG >100,000 = 4 points, pulmonary metastases = 4 points) mandates combination therapy. **Clinical Pearl:** Methotrexate monotherapy is reserved for low-risk disease (FIGO <7). Once metastases or high β-hCG is present, combination regimens are essential to prevent chemotherapy resistance and ensure cure. **Warning:** Do NOT use single-agent methotrexate in high-risk disease — this is a common exam trap. Failure to escalate therapy early leads to drug-resistant disease and poor outcomes.