{"entity":{"id":"high-risk-gtn","kind":"cancer","name":"High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk)","aka":["High-risk GTN","Metastatic gestational choriocarcinoma","Ultra-high-risk gestational trophoblastic neoplasia (score 13 or more)","Choriocarcinoma after term pregnancy"],"tldr":"High-risk gestational trophoblastic neoplasia is the aggressive form of this pregnancy-related cancer, usually choriocarcinoma that has spread to the lungs, liver or brain and produces very high hCG. It is treated with the multi-drug EMA-CO regimen, started gently in the sickest women to avoid early deaths, and most are cured; resistant disease gets platinum regimens, immunotherapy or surgery.","summary":"High-risk gestational trophoblastic neoplasia, a FIGO 2000 score of 7 or more, is usually gestational choriocarcinoma, a tumour of syncytiotrophoblast and cytotrophoblast that follows a molar, term, miscarried or ectopic pregnancy and spreads through the blood to the lungs, vagina, liver and brain; it bleeds readily and produces enormous amounts of hCG. Choriocarcinoma after a term pregnancy is often diagnosed late because nobody suspects it, and any woman of reproductive age with unexplained metastases should have an hCG measured. Multi-agent chemotherapy became standard in the 1980s when Kenneth Bagshawe's group at Charing Cross developed EMA-CO (etoposide, methotrexate and actinomycin D alternating weekly with cyclophosphamide and vincristine), which cures more than nine in ten women with high-risk disease and remains the first-line regimen in the NCCN and FIGO guidelines.\n\nThe main causes of death are early haemorrhage and organ failure in women with very high tumour burden, and late resistance. For ultra-high-risk disease (score 13 or more, or liver or brain metastases) the Charing Cross and Sheffield centres showed that starting with one or two cycles of low-dose etoposide and cisplatin before EMA-CO prevents the early deaths caused by tumour breakdown and haemorrhage, and brain metastases are treated with higher-dose intrathecal or systemic methotrexate with or without radiotherapy or surgery. Women whose hCG plateaus on EMA-CO switch to EP-EMA (etoposide and cisplatin alternating with EMA) or to TP/TE (paclitaxel with cisplatin alternating with paclitaxel and etoposide), which cure most of the remainder; hysterectomy, lung resection or excision of a resistant focus localised by PET can remove the last chemoresistant deposit, and high-dose chemotherapy with autologous stem cell rescue has cured a few. Because trophoblast expresses PD-L1, pembrolizumab produced durable remissions in women with multiply resistant disease in the first case series (Lancet 2017), and avelumab and pembrolizumab are now tested as salvage and as first-line partners. hCG follow-up runs for at least a year, often longer, before pregnancy is allowed, and late effects of etoposide, including a small excess of leukaemia, are monitored.","asOf":"2026-09-18","wikipedia":"https://en.wikipedia.org/wiki/Choriocarcinoma","links":[{"label":"FIGO cancer report: gestational trophoblastic disease (2021)","url":"https://doi.org/10.1002/ijgo.13877"},{"label":"NCCN Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Choriocarcinoma"}],"tags":["subtype-page","gynaecologic"],"related":["low-risk-gtn","placental-site-trophoblastic-tumour","gestational-trophoblastic","non-seminoma"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","checkpoint-inhibitor","ultrasound","mri","ct","pet-ct","imrt-igrt","sbrt","autologous-stem-cell-transplant","serum-tumour-markers"],"targets":["pdl1","pd1"],"drugs":["etoposide","methotrexate","dactinomycin","cyclophosphamide","vincristine","cisplatin","paclitaxel","pembrolizumab","avelumab"],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-markers","staging-systems"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bower-ema-co-high-risk-gtn-charing-cross-jco-1997","paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021","paper-figo-2000-staging-gestational-trophoblastic-neoplasia-ijgo-2002"],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"A minority of gestational trophoblastic neoplasia, often choriocarcinoma after a non-molar pregnancy with metastases to lung, liver or brain and very high hCG; cure rates still exceed nine in ten with multi-agent chemotherapy.","subtypes":["High-risk gestational choriocarcinoma with lung metastases (FIGO score 7 to 12)","Ultra-high-risk gestational trophoblastic neoplasia (score 13 or more; induction low-dose etoposide-cisplatin)","Gestational trophoblastic neoplasia with liver metastases","Gestational trophoblastic neoplasia with brain metastases (high-dose methotrexate, radiotherapy or surgery)","Choriocarcinoma after term pregnancy or miscarriage (late diagnosis)","EMA-CO-resistant gestational trophoblastic neoplasia (EP-EMA, TP/TE, pembrolizumab, surgery)"],"biomarkers":["Serum hCG (very high; response and surveillance)","FIGO 2000 score (7 or more high risk; 13 or more ultra-high risk)","Sites of metastasis on CT, MRI of brain and pelvic ultrasound (liver and brain define ultra-high risk)","Cerebrospinal fluid to serum hCG ratio (brain involvement)","Genotyping to confirm gestational origin and identify the causative pregnancy","PD-L1 expression (universal; checkpoint inhibitor rationale)"],"standardOfCare":[{"setting":"Staging","approach":"hCG, chest CT, brain MRI, abdominal imaging, pelvic Doppler ultrasound and FIGO scoring; genotyping where the antecedent pregnancy is unclear.","refs":["ct","mri","ultrasound","tumour-markers","staging-systems"],"guideline":{"version":"NCCN Guidelines: Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"}},{"setting":"High-risk disease, first line","approach":"EMA-CO (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine) until hCG normalises plus at least three consolidation cycles.","refs":["etoposide","methotrexate","dactinomycin","cyclophosphamide","vincristine","cytotoxic-chemotherapy"],"guideline":{"version":"NCCN Guidelines: Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"}},{"setting":"Ultra-high-risk disease","approach":"Induction low-dose etoposide and cisplatin for one to three cycles before EMA-CO to prevent early death from haemorrhage and organ failure.","refs":["etoposide","cisplatin"],"guideline":{"version":"NCCN Guidelines: Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"}},{"setting":"Brain metastases","approach":"High-dose systemic and intrathecal methotrexate within EMA-CO, with whole-brain or stereotactic radiotherapy or craniotomy for bleeding or single lesions.","refs":["methotrexate","imrt-igrt","sbrt"],"guideline":{"version":"NCCN Guidelines: Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"}},{"setting":"Resistant or relapsed disease","approach":"EP-EMA or TP/TE; resection of a resistant focus (hysterectomy, lung wedge); pembrolizumab or avelumab; high-dose chemotherapy with autologous rescue in exceptional cases.","refs":["etoposide","cisplatin","paclitaxel","pembrolizumab","avelumab","autologous-stem-cell-transplant","pet-ct"],"guideline":{"version":"NCCN Guidelines: Gestational Trophoblastic Neoplasia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489"}}],"stateOfArt":["EMA-CO cures more than nine in ten women with high-risk disease.","Low-dose induction chemotherapy has largely eliminated early deaths in ultra-high-risk disease.","PD-1 and PD-L1 antibodies rescue women with multiply resistant disease."],"history":[{"year":1956,"title":"Methotrexate cures metastatic choriocarcinoma at the NCI","refs":["methotrexate"]},{"year":1976,"title":"Bagshawe develops the first prognostic scoring system at Charing Cross","refs":["staging-systems"]},{"year":1986,"title":"EMA-CO reported as a regimen for high-risk disease","refs":["etoposide","methotrexate","dactinomycin","cyclophosphamide","vincristine"]},{"year":2000,"title":"FIGO combines anatomical stage and prognostic score","refs":["staging-systems"]},{"year":2013,"title":"Low-dose induction etoposide-cisplatin shown to reduce early deaths in ultra-high-risk disease","refs":["etoposide","cisplatin"]},{"year":2017,"title":"Pembrolizumab produces durable remissions in chemoresistant gestational trophoblastic neoplasia","refs":["pembrolizumab"]}],"pipeline":["pembrolizumab","avelumab"],"openProblems":["EMA-CO has never been tested against any other regimen in a randomised trial.","Late diagnosis of choriocarcinoma after term pregnancy still costs lives.","Etoposide raises the long-term risk of leukaemia and its dose cannot easily be reduced.","Where checkpoint inhibitors belong in the sequence is being worked out from small series."],"parent":"gestational-trophoblastic"},"route":"/cancers/high-risk-gtn/","neighbours":{"cancer":[{"id":"gestational-trophoblastic","kind":"cancer","name":"Gestational trophoblastic neoplasia","route":"/cancers/gestational-trophoblastic/"},{"id":"low-risk-gtn","kind":"cancer","name":"Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6)","route":"/cancers/low-risk-gtn/"},{"id":"non-seminoma","kind":"cancer","name":"Non-seminomatous germ cell tumour","route":"/cancers/non-seminoma/"},{"id":"placental-site-trophoblastic-tumour","kind":"cancer","name":"Placental-site trophoblastic tumour and epithelioid trophoblastic tumour","route":"/cancers/placental-site-trophoblastic-tumour/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"serum-tumour-markers","kind":"technology","name":"Serum tumour markers: proper use and misuse","route":"/technologies/serum-tumour-markers/"},{"id":"ultrasound","kind":"technology","name":"Ultrasound","route":"/technologies/ultrasound/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dactinomycin","kind":"drug","name":"Dactinomycin (actinomycin D)","route":"/drugs/dactinomycin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"staging-systems","kind":"term","name":"Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)","route":"/terms/staging-systems/"},{"id":"tumour-markers","kind":"term","name":"Tumour markers (CEA, LDH, chromogranin, thyroglobulin)","route":"/terms/tumour-markers/"}],"paper":[{"id":"paper-bower-ema-co-high-risk-gtn-charing-cross-jco-1997","kind":"paper","name":"EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients","route":"/key-papers/paper-bower-ema-co-high-risk-gtn-charing-cross-jco-1997/"},{"id":"paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021","kind":"paper","name":"FIGO Cancer Report 2021: diagnosis and management of gestational trophoblastic disease","route":"/key-papers/paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021/"},{"id":"paper-figo-2000-staging-gestational-trophoblastic-neoplasia-ijgo-2002","kind":"paper","name":"FIGO staging for gestational trophoblastic neoplasia 2000","route":"/key-papers/paper-figo-2000-staging-gestational-trophoblastic-neoplasia-ijgo-2002/"}]}}