A 32-year-old woman is diagnosed with persistent gestational trophoblastic disease (PGTD) 6 weeks after evacuation of a complete molar pregnancy. β-hCG is 850 mIU/mL, FIGO score is 4 (low-risk), and there are no metastases on imaging. What is the drug of choice for treatment?

## Low-Risk Gestational Trophoblastic Neoplasia: Single-Agent Chemotherapy ### Risk Stratification in This Case - **FIGO score = 4** (low-risk, threshold is <7) - **β-hCG = 850 mIU/mL** (well below 100,000 threshold) - **No metastases** - Interval from evacuation: 6 weeks (recent) **Key Point:** Low-risk GTN (FIGO score <7) is treated with single-agent chemotherapy; multiagent regimens are reserved for high-risk disease and unnecessarily increase toxicity in curable low-risk patients. ### First-Line Single-Agent Options for Low-Risk GTN | Agent | Cure Rate | Advantages | Use | |-------|-----------|------------|-----| | **Methotrexate (high-dose)** | 85–90% | First-line, well-tolerated, reversible toxicity | **Preferred initial choice** | | Dactinomycin | 85–90% | Alternative if MTX contraindicated or resistance | Second-line | | Chlorambucil | ~80% | Rarely used now | Historical | **High-Yield:** Methotrexate high-dose (1 g/m² IV weekly) with folinic acid (leucovorin) rescue is the **gold-standard first-line** for low-risk GTN. It achieves cure in 85–90% of patients with minimal toxicity. ### Methotrexate Dosing & Monitoring 1. **Dose:** 1 g/m² IV weekly (or 50 mg IM weekly for lower-risk cases) 2. **Folinic acid rescue:** 10–15 mg PO 6-hourly × 4 doses, starting 24 hours post-MTX 3. **Monitoring:** β-hCG weekly until undetectable, then monthly × 12 months 4. **Cure criteria:** Negative β-hCG × 3 consecutive weeks **Clinical Pearl:** If β-hCG plateaus or rises during single-agent therapy, switch to alternative single-agent (dactinomycin) or escalate to multiagent (EMA-CO) if resistance confirmed. ~10–15% of low-risk patients require second-line therapy. **Mnemonic:** **"Low-risk GTN = Single agent; High-risk GTN = Multiple agents"** — match therapy intensity to disease risk. ### Why EMA-CO Is Overkill Here EMA-CO is reserved for high-risk GTN (FIGO ≥7) because: - Unnecessary toxicity in curable low-risk disease - Increased infection risk, alopecia, and infertility risk - No survival advantage over single-agent therapy in low-risk patients - Cost and complexity unjustified