What is the first step in managing a patient after evacuation of a molar pregnancy with persistently elevated β‑hCG?

First Step: Calculate FIGO Risk Score and Obtain Staging Workup

The first step after molar evacuation with persistently elevated β-hCG is to calculate the FIGO risk score and perform staging workup including history, physical examination, Doppler pelvic ultrasound, and chest X-ray to determine whether the patient has low-risk or high-risk gestational trophoblastic neoplasia (GTN), which will dictate whether single-agent or multi-agent chemotherapy is required. 1

Understanding Persistent β-hCG After Molar Evacuation

Persistent GTN is diagnosed when any of the following criteria are met after molar evacuation 1:

• β-hCG plateau for 4 consecutive values over 3 weeks
• β-hCG rise >10% for 3 consecutive values over 2 weeks
• β-hCG persistence 6 months or more after evacuation

Critical Initial Assessment

Required Staging Workup 1

• History and physical examination focusing on symptoms of metastatic disease
• Doppler pelvic ultrasound to confirm absence of pregnancy, measure uterine size, and delineate tumor volume and vascularity
• Chest X-ray to assess for pulmonary metastases
• If chest X-ray shows no metastatic disease, no further imaging is needed before treatment 1

FIGO Risk Scoring System

The FIGO score determines treatment intensity 1:

• Low-risk (score <7): Single-agent chemotherapy with methotrexate/folinic acid
• High-risk (score ≥7): Multi-agent chemotherapy with EMA-CO regimen

Treatment Algorithm Based on Risk Stratification

For Low-Risk Disease (FIGO Score <7)

Methotrexate with folinic acid (MTX/FA) is the standard first-line treatment 1:

• Methotrexate 50 mg IM every 48 hours for 4 doses
• Folinic acid 15 mg orally 30 hours after each MTX dose
• Courses repeated every 2 weeks until β-hCG normalizes, then continue for 6 additional weeks after normalization 1

Important caveat: Patients scoring 5-6 have only 30% cure rate with low-risk therapy, and 70% will develop MTX/FA resistance requiring escalation 1

For High-Risk Disease (FIGO Score ≥7)

EMA-CO multi-agent chemotherapy is required 1:

• This regimen achieves 90.6% remission rates in high-risk patients 1
• Single-agent therapy is inadequate and unlikely to cure these patients 1

Alternative Consideration: Repeat Uterine Evacuation

Before initiating chemotherapy, repeat dilation and curettage or hysterectomy can be considered for persistent postmolar GTN 1:

• In one study, 68% of women who underwent second uterine evacuation had no further disease or chemotherapy requirements 1
• Best candidates for repeat evacuation: patients without histologic confirmation of persistent trophoblastic disease and urinary hCG <1,500 IU/L 1
• If repeat evacuation is performed, follow with β-hCG monitoring every 2 weeks until 3 consecutive normal assays, then monthly for 6 additional months 1

Common Pitfalls to Avoid

Do Not Delay Treatment in Truly Persistent Disease

• Patients with metastatic disease, histopathologic choriocarcinoma, or persistent hCG elevation (plateau/rise) should proceed directly to chemotherapy based on FIGO scoring 1
• Early deaths from hemorrhage or metabolic complications occur when treatment is delayed in extensive disease 1

Special Consideration: Falling but Elevated β-hCG at 6 Months

Recent evidence challenges the FIGO 2000 recommendation to treat all patients with raised but falling β-hCG at 6 months 2, 3:

• 86% of patients with falling β-hCG at 6 months achieve spontaneous remission without chemotherapy 3
• Only 11-20% develop GTN requiring treatment 2, 3
• Close surveillance with regular β-hCG and radiological monitoring may avoid unnecessary chemotherapy exposure 2, 3
• However, patients who eventually require chemotherapy after expectant management have higher FIGO scores (median 4 vs 2) and longer time to remission 2

Risk Stratification Based on Early β-hCG Trends

Early post-evacuation β-hCG levels predict persistence risk 4:

• β-hCG <50 mIU/mL at any time: ≤1.1% risk of persistent GTN 4
• β-hCG <200 mIU/mL at week 4 or <100 mIU/mL at week 6: <9% risk 4
• β-hCG >2,000 mIU/mL at week 4: 63.8% risk of persistent disease 4

Monitoring During Treatment

• β-hCG monitoring every 1-2 weeks until normalization (3 consecutive normal assays) 1
• After normalization, measure β-hCG twice in 3-month intervals to ensure levels remain normal 1
• Continue chemotherapy for 6 weeks after β-hCG normalization to eliminate residual disease and minimize relapse risk 1