Prognostic Factors for Gestational Trophoblastic Neoplasia
The FIGO 2000 prognostic scoring system is the critical framework for GTN risk stratification, with metastatic site (particularly brain and liver involvement) being the single most important prognostic factor for mortality, followed by pre-treatment hCG level, interval from antecedent pregnancy, and prior chemotherapy resistance. 1
The FIGO Prognostic Scoring System
The FIGO scoring system has been the international standard since 2002 for predicting resistance to single-agent chemotherapy and guiding treatment selection. 1 A total score of 0-6 indicates low-risk disease with excellent prognosis (approaching 100% cure rate), while a score ≥7 indicates high-risk disease requiring multi-agent chemotherapy. 1, 2
Key Prognostic Variables Assessed
The FIGO system evaluates seven critical factors: 1
Tumor Volume Indicators:
- hCG level: Scored 0 for <1,000 IU/L, 1 for 1,000-10,000 IU/L, 2 for 10,000-100,000 IU/L, and 4 for >100,000 IU/L 1
- Number of metastases: Scored 0 for none, 1 for 1-4 lesions, 2 for 5-8 lesions, and 4 for >8 lesions 1
- Largest tumor mass: Scored 1 for 3-5 cm and 2 for >5 cm 1
Site of Metastases (Most Critical for Mortality):
- Lung metastases: Score 0 (most favorable) 1
- Spleen and kidney: Score 1 1
- GI tract: Score 2 1
- Brain and liver: Score 4 (highest mortality risk and significantly alters management) 1
Disease Duration:
- Interval from antecedent pregnancy to chemotherapy: Scored 0 for <4 months, 1 for 4-6 months, 2 for 7-12 months, and 4 for >12 months 1, 3
Treatment History:
- Prior chemotherapy: Scored 2 for single drug failure and 4 for ≥2 drug failures 1
Patient Factors:
- Age: Scored 0 for <40 years and 1 for ≥40 years 1
- Antecedent pregnancy type: Scored 0 for mole, 1 for abortion, and 2 for term pregnancy 1
Independent Prognostic Factors Beyond FIGO Score
Doppler pulsatility index of the uterine artery is an independent prognostic factor for resistance to single-agent methotrexate therapy, with higher indices predicting treatment failure. 1, 4
Lung nodule size in metastatic disease independently predicts both resistance and recurrence risk, with lesions >2 cm requiring more aggressive initial management. 1, 4
Pre-treatment hCG level >400,000 IU/L warrants multi-agent chemotherapy even in patients with otherwise low-risk scores. 1, 2
Clinical Implications for Treatment Selection
Low-risk disease (score 0-6):
- Single-agent chemotherapy with methotrexate or actinomycin D achieves cure rates approaching 100% 1, 2
- Resistance to first-line single agent occurs in approximately 12-25% of cases 4, 3
High-risk disease (score ≥7):
- Multi-agent chemotherapy (EMA/CO or MEA) is mandatory, with survival rates of 80-94% 2, 5, 6
- Early death within 4 weeks of treatment initiation occurs in approximately 1% of cases 6
- Overall survival improved from 77.8% (1962-1978) to 91.8% (1979-2006) with modern protocols 3
Critical Pitfalls to Avoid
Do not rely solely on anatomical staging for treatment decisions—the prognostic score is what determines therapy, not the stage alone. 1
Brain or liver metastases require immediate MRI brain and CT body imaging when chest X-ray shows pulmonary lesions >1 cm, as these sites carry the highest mortality risk. 1
Duration of disease >4 months significantly increases resistance to chemotherapy (35% vs 17% for ≤4 months), emphasizing the importance of early hCG monitoring and prompt treatment initiation. 3
Prior unsuccessful chemotherapy at another institution dramatically increases resistance rates (63% vs 17% for primary treatment at specialized centers), highlighting the critical importance of centralized care at GTD reference centers. 3