What is the role of the World Health Organization (WHO) prognostic score in managing Gestational Trophoblastic Disease (GTD)?

WHO Prognostic Score in Gestational Trophoblastic Disease

The WHO (FIGO 2000) prognostic scoring system is the mandatory standard for all physicians treating gestational trophoblastic neoplasia (GTN) to predict resistance to single-agent chemotherapy and determine whether patients require single-agent versus multi-agent treatment. 1

Purpose and Clinical Application

The WHO prognostic score serves as the primary decision-making tool that directly determines treatment intensity and predicts outcomes in GTN management 1:

• Scores 0-6 (Low-Risk): Patients receive single-agent chemotherapy with methotrexate or actinomycin D, achieving cure rates approaching 100% 1, 2
• Scores ≥7 (High-Risk): Patients have almost no chance of cure with single-agent therapy and require multi-agent chemotherapy (typically EMA/CO), with survival rates of 80-90% 1, 2

The Eight Prognostic Factors Assessed

The scoring system evaluates the following variables, with points assigned as shown 1:

Patient and Pregnancy Factors

• Age: <40 years (0 points) vs ≥40 years (1 point) 1
• Antecedent pregnancy: Mole (0 points), abortion (1 point), or term pregnancy (2 points) 1
• Interval from end of pregnancy to chemotherapy: <4 months (0 points), 4-6 months (1 point), 7-12 months (2 points), >12 months (4 points) 1

Tumor Burden Markers

• Serum hCG level (IU/L): <10³ (0 points), 10³-10⁴ (1 point), 10⁴-10⁵ (2 points), >10⁵ (4 points) 1
• Number of metastases: 0 (0 points), 1-4 (1 point), 5-8 (2 points), >8 (4 points) 1
• Largest tumor mass: 3-5 cm (1 point), >5 cm (2 points) 1

High-Risk Features

• Site of metastases: Lung (0 points), spleen/kidney (1 point), GI tract (2 points), brain/liver (4 points) 1
• Prior chemotherapy: Single drug (2 points), ≥2 drugs (4 points) 1

Critical Score Thresholds and Mortality Risk

Patients with FIGO scores ≥13 represent an ultra-high-risk subgroup with a 38.4% five-year mortality rate and account for 52% of all GTN deaths, despite representing only a small fraction of cases. 3

Key mortality data by risk stratification 3:

• Overall GTN mortality: 2% five-year rate 3
• High-risk (score ≥7): 12% five-year mortality 3
• Ultra-high-risk (score ≥13): 38.4% five-year mortality, with 75% of these deaths occurring within 4 weeks of treatment initiation 3

Patients with scores ≥13 require immediate referral to highly specialized GTD centers and may benefit from low-dose etoposide-cisplatin induction chemotherapy before standard multi-agent regimens 3.

Important Clinical Nuances

Treatment Resistance Patterns

Within the low-risk category, patients with WHO scores of 5-6 have significantly higher resistance rates compared to scores ≤4 (OR 6.56,95% CI 1.73-24.27) 4. These patients may warrant closer monitoring or consideration of more intensive initial therapy 4.

Exception: PSTT and ETT

The WHO scoring system is NOT valid for placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT). 1 These entities require FIGO anatomic staging only (Stage I-IV) to guide treatment intensity, as they have distinct biological behavior with less hCG production, slower growth, and slightly reduced chemosensitivity 1.

Staging Investigations Required for Accurate Scoring

To properly calculate the WHO score, the following workup is mandatory 1:

• Serum hCG level (quantitative) 1
• Chest radiograph (to identify pulmonary metastases) 1
• Pelvic Doppler ultrasound (to assess uterine disease and vascularity) 1
• If CXR shows lesions: Brain MRI and CT chest/abdomen/pelvis to identify brain or liver metastases, which carry 4 points each and dramatically alter prognosis 1
• Consider lumbar puncture if brain metastases suspected (CSF:serum hCG ratio >1:60 suggests occult CNS disease) 1

Common Pitfalls to Avoid

• Do not skip comprehensive staging in patients with visible chest X-ray lesions, as undetected brain or liver metastases will result in undertreatment 1
• Do not apply the WHO score to PSTT/ETT - use anatomic staging only for these histologic subtypes 1
• Do not delay treatment in ultra-high-risk patients (score ≥13) - mean time from diagnosis to treatment should be <2 days, and these patients require immediate specialized center referral 3, 4
• Recognize that patients with hCG >400,000 IU/L should receive multi-agent chemotherapy regardless of total score, as single-agent therapy is inadequate despite potentially low calculated scores 2