What is the management for a female patient of childbearing age with Gestational Trophoblastic Disease (GTD) according to South African guidelines?

Management of Gestational Trophoblastic Disease According to South African Guidelines

While specific South African GTD guidelines are not provided in the evidence, South Africa follows international consensus guidelines from the European Organisation for Treatment of Trophoblastic Disease (EOTTD), European Society of Gynaecologic Oncology (ESGO), and International Federation of Gynecology and Obstetrics (FIGO), which represent the global standard of care for GTD management. 1

Initial Diagnosis and Evacuation

For Suspected Hydatidiform Mole

• Perform ultrasound examination as the primary diagnostic tool 1
• Obtain baseline serum hCG, chest X-ray (if clinical suspicion of metastases), blood group and crossmatch 1
• Evacuate the uterus by suction dilation and curettage under anesthesia as the standard approach 1, 2
• Administer anti-D immunization to Rh-negative women 1
• Send tissue for histopathology examination, with reference pathology review at a GTD center within 2 weeks 1

Critical pitfall: Blood transfusion may be urgently needed during evacuation—inform the anesthetist beforehand 1

Post-Evacuation Surveillance

hCG Monitoring Protocol

• Measure serum hCG at least once every 2 weeks until normalization 1
• For partial hydatidiform mole (PHM): Require one additional normal hCG value over 1 month before discharge 1
• For complete hydatidiform mole (CHM): Continue monthly hCG monitoring for up to 6 months after normalization 1

Diagnosis of Gestational Trophoblastic Neoplasia (GTN)

GTN is diagnosed when hCG plateaus over 3 values one week apart OR rises over 2 values one week apart (FIGO criteria) 1

Risk Stratification Using FIGO Scoring

All patients developing GTN must undergo comprehensive staging before treatment:

Minimal Requirements for Staging 1

• Urgent patient review and discussion with GTD expert
• History, examination, serum hCG
• Pelvic ultrasound with Doppler and chest X-ray
• If chest X-ray shows metastases ≥1 cm: Obtain contrast CT chest, MRI brain, and CT/MRI abdomen/pelvis 1

FIGO Prognostic Scoring 1, 2

Calculate score based on: age, antecedent pregnancy type, interval from index pregnancy, pretreatment hCG level, largest tumor size, sites of metastases, number of metastases, and previous failed chemotherapy 1

• Low-risk GTN: Score 0-6
• High-risk GTN: Score ≥7

Important caveat: FIGO scoring is NOT valid for placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)—these require FIGO staging only 1, 2

Treatment Algorithm

Low-Risk GTN (FIGO Score 0-6)

First-line treatment: Single-agent chemotherapy 1, 2

• Methotrexate with folinic acid (MTX/FA) OR Actinomycin-D (Act-D) 1, 2
• MTX/FA regimen: 0.4 mg/kg (maximum 25 mg) IV days 1-5 every 2 weeks 1
• Act-D: 1.25 mg/m² IV every 2 weeks 1
• Continue for at least 2 consolidation cycles after hCG normalization 1, 2

Alternative options in selected cases: 1

• Second curettage (40% cure rate independent of endometrial thickness)
• Hysterectomy if no desire for future fertility and disease confined to uterus

Management of Resistance to First Single Agent

• Monitor hCG at least once every 2 weeks during treatment 1
• If hCG plateaus or rises: Change to alternate single agent OR switch to EMA/CO multiagent chemotherapy 1
• If hCG >1,000 IU/L at resistance, strongly consider EMA/CO 1

Critical pitfall: Do NOT use weekly intramuscular methotrexate—it is less effective than 5- or 8-day regimens 2

High-Risk GTN (FIGO Score ≥7)

All high-risk patients MUST be referred to and treated at a specialized GTD center 1

First-line treatment: EMA/CO multiagent chemotherapy 1, 2

• EMA/CO = Etoposide, Methotrexate, Actinomycin-D, Cyclophosphamide, Vincristine
• Achieves 80-90% survival rates 2
• Continue for 3-4 consolidation cycles after hCG normalization 1
• For CNS metastases: Increase MTX to 1 g/m² in EMA/CO regimen 1
• For liver with brain metastases: EMA/EP (or FAEV) is favored 1

Management of Recurrent or Chemoresistant GTN

For recurrence after remission: 1

• Exclude new pregnancy first
• Obtain imaging (FDG-PET-CT can help exclude multiple metastases) 1
• If resectable single focus: Surgical resection may avoid need for chemotherapy 1
• If non-resectable or hCG doesn't normalize post-surgery: Multiagent chemotherapy is required 1

For high-risk GTN failing EMA/CO: 1, 2

• Offer platinum-based chemotherapy (EP/EMA or TE/TP regimens) 1, 2
• After failure of platinum/etoposide or FAEV: Anti-PD-1 immunotherapy is indicated 1
• Immunotherapy shows approximately 70% response rates 1
• Surgery for isolated chemoresistant foci (pulmonary resection, craniotomy, liver metastases resection) 1, 2

Special Entities: PSTT and ETT

These require different management as they are less chemosensitive: 2

Stage I Disease (Confined to Uterus)

• Hysterectomy with pelvic lymph node sampling is recommended if presenting within 4 years 2

Metastatic Disease

• Multi-agent chemotherapy with EP/EMA 2
• Surgically remove residual masses—they can harbor microscopic disease 2

Critical pitfall: PSTT typically has low hCG levels relative to tumor volume—histological confirmation is essential 2

Critical Safety Warnings

Never biopsy visible lesions in the lower genital tract—severe hemorrhage risk from fragile trophoblastic tumor vessels 2

Avoid multiple repeat curettages—they rarely prevent need for chemotherapy and cause endometrial scarring 1, 2

Consider phantom hCG if hCG is elevated with no evidence of disease on imaging—different assays detect different hCG isoforms 2

Post-Treatment Surveillance

• Cured patients should be offered surveillance for at least 2 years 1
• Monitor hCG regularly during this period to detect early recurrence

Referral Criteria

Mandatory referral to GTD center: 1, 2

• All high-risk GTN cases (FIGO score ≥7)
• All PSTT and ETT cases
• Any low-risk GTN with resistance to first-line single agent
• Complex cases requiring surgical intervention for metastases
• Discuss treatment with GTD center BEFORE starting therapy 1