Gestational trophoblastic neoplasia
Cancers that grow from placental tissue after a pregnancy. They make a hormone (hCG) that acts as a perfect blood test, and they were the first solid cancer ever cured by chemotherapy. Immunotherapy now rescues the few that resist drugs.
Gestational trophoblastic neoplasia (GTN) follows a molar pregnancy (complete or partial hydatidiform mole) or, less often, any pregnancy, and includes invasive mole, choriocarcinoma, placental-site and epithelioid trophoblastic tumours. Serum hCG tracks disease burden with unique precision, so diagnosis is usually made from a plateau or rise in hCG after molar evacuation without histology. The FIGO 2000 prognostic score separates low-risk (single-agent methotrexate or actinomycin D) from high-risk disease (multi-agent EMA-CO), with ultra-high-risk patients started on low-dose induction etoposide-cisplatin to prevent early death.
GTN is highly immunogenic (paternal antigens, PD-L1 expression), and PD-1 blockade produced durable complete remissions in chemotherapy-resistant disease (pembrolizumab, Ghorani 2017; avelumab TROPHIMMUN 2020), now in guidelines. Placental-site and epithelioid tumours are chemo-resistant and treated by hysterectomy. Outcomes depend on centralised care with hCG registries (Charing Cross, Sheffield, Brewer).
State of the art today
- The only cancer routinely diagnosed and monitored by a hormone alone, with near-universal cure.
- Immunotherapy cures a majority of drug-resistant cases; trials (TROPHAMET, TROPHIMMUN) now test it earlier to avoid chemotherapy.
- Centralised registries remain the model for how rare cancers should be managed.
Molar pregnancy in ~1 per 1,000 pregnancies (higher in Asia); GTN requiring chemotherapy in ~1 per 40,000 pregnancies; cure rates approach 100% in low-risk and >90% in high-risk disease.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Single-agent methotrexate (8-day regimen) or pulsed actinomycin D; switch agent on resistance; consolidate 3 cycles after hCG normalisation.
EMA-CO (etoposide, methotrexate, actinomycin D / cyclophosphamide, vincristine); induction low-dose EP for ultra-high-risk; EP-EMA or TP/TE at relapse; surgery for resistant foci.
PD-1/PD-L1 blockade (pembrolizumab, avelumab), high-dose chemotherapy with stem-cell rescue in selected cases, hysterectomy or metastasectomy.
Subtypes & biomarkers
top- Complete and partial hydatidiform mole (premalignant)
- Invasive mole
- Gestational choriocarcinoma
- Placental-site trophoblastic tumour (PSTT)
- Epithelioid trophoblastic tumour (ETT)
- Serum hCG (diagnosis, staging, response, surveillance)
- FIGO 2000 prognostic score (low ≤6, high ≥7, ultra-high ≥13)
- Hyperglycosylated hCG / hCG-free beta (PSTT)
- Genotyping to confirm gestational origin
- PD-L1 (expressed in nearly all GTN)
Target prevalence in this cancer
- 1956Methotrexate cures metastatic choriocarcinoma (Li, Hertz, Spencer)
The first solid tumour cured by chemotherapy.
- 1973Charing Cross hCG surveillance service established
Model for centralised GTD registries.
- 1979EMA-CO introduced by Bagshawe for high-risk disease
- 2000FIGO 2000 staging and prognostic score
- 2017Pembrolizumab cures chemoresistant GTN (Ghorani, Lancet)
- 2020TROPHIMMUN: avelumab in methotrexate-resistant low-risk GTN
Open problems
- Late diagnosis where hCG surveillance after molar pregnancy is absent (much of the world).
- Fertility and psychological burden of a pregnancy-related cancer.
- PSTT/ETT chemo-resistance.
- Cumulative etoposide exposure and second cancers.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Pembrolizumab
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Pembrolizumab
- GOG FoundationPhiladelphia, PA, USvia Pembrolizumab
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- Institut Jules BordetBrussels, BEvia Pembrolizumab
- via Pembrolizumab
Questions to ask
topQuestions to ask your oncologist about Gestational trophoblastic neoplasia
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Serum hCG, FIGO 2000 prognostic score, Hyperglycosylated hCG / hCG-free beta, Genotyping to confirm gestational origin, PD-L1), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Complete and partial hydatidiform mole, Invasive mole, Gestational choriocarcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Low-risk GTN (FIGO score 0-6)
- For my situation (low-risk gtn (figo score 0-6)), which of the standard options do you recommend and why?Why: Guideline options include: Single-agent methotrexate (8-day regimen) or pulsed actinomycin D; switch agent on resistance; consolidate 3 cycles after hCG normalisation.
- Am I a candidate for Methotrexate, Dactinomycin (actinomycin D), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
High-risk GTN (score ≥7)
- For my situation (high-risk gtn (score ≥7)), which of the standard options do you recommend and why?Why: Guideline options include: EMA-CO (etoposide, methotrexate, actinomycin D / cyclophosphamide, vincristine); induction low-dose EP for ultra-high-risk; EP-EMA or TP/TE at relapse; surgery for resistant foci.
- Am I a candidate for Etoposide, Methotrexate, Dactinomycin (actinomycin D) or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Chemotherapy-resistant GTN
- For my situation (chemotherapy-resistant gtn), which of the standard options do you recommend and why?Why: Guideline options include: PD-1/PD-L1 blockade (pembrolizumab, avelumab), high-dose chemotherapy with stem-cell rescue in selected cases, hysterectomy or metastasectomy.
- Am I a candidate for Pembrolizumab, Avelumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
PSTT / ETT
- For my situation (pstt / ett), which of the standard options do you recommend and why?Why: Guideline options include: Hysterectomy; platinum-etoposide chemotherapy if metastatic or >4 years from antecedent pregnancy.
- Am I a candidate for Cisplatin, Etoposide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Pembrolizumab, Avelumab?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Late diagnosis where hCG surveillance after molar pregnancy is absent (much of the world)”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Fertility and psychological burden of a pregnancy-related cancer”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
10targets
3drugs
8companies
2pathways
1terms
2Latest papers
topQuery for this cancer: (TITLE:"Gestational trophoblastic neoplasia" OR ABSTRACT:"Gestational trophoblastic neoplasia" OR TITLE:"GTN" OR ABSTRACT:"GTN" OR TITLE:"Choriocarcinoma" OR ABSTRACT:"Choriocarcinoma" OR TITLE:"Molar pregnancy" OR ABSTRACT:"Molar pregnancy" OR TITLE:"Placental site trophoblastic tumour" OR ABSTRACT:"Placental site trophoblastic tumour") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Gestational trophoblastic neoplasia, not a curated reading list.
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