# Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6)

Source: https://onco.cc/cancers/low-risk-gtn/  
OnCo record `low-risk-gtn` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Low-risk gestational trophoblastic neoplasia is the mild form of this rare pregnancy-related cancer, usually found when the pregnancy hormone hCG fails to fall after removal of a molar pregnancy. It is cured in almost every woman with a single chemotherapy drug, methotrexate or actinomycin D, given until the hormone level is normal, and most go on to have normal pregnancies afterwards.

## Summary

Gestational trophoblastic neoplasia arises from the placental trophoblast of a pregnancy, most often a complete or partial hydatidiform mole, and is unique among cancers in producing a near-perfect tumour marker, human chorionic gonadotropin (hCG), which is used for diagnosis, staging, monitoring and follow-up. After evacuation of a complete mole about 15 percent of women, and after a partial mole under 1 percent, develop neoplasia, detected by a plateau or rise in serial hCG without any need for biopsy. The FIGO 2000 scoring system combines age, antecedent pregnancy, interval, hCG level, tumour size, site and number of metastases and prior chemotherapy into a score; 6 or below is low risk and predicts response to single-agent chemotherapy. Low-risk disease is typically an invasive mole or choriocarcinoma confined to the uterus or with small lung metastases.

Single-agent chemotherapy cures nearly all patients. Methotrexate, the first drug ever to cure a metastatic cancer when Min Chiu Li used it for choriocarcinoma in 1956, is given as an eight-day regimen alternating with folinic acid (the Charing Cross schedule) or weekly, and actinomycin D as a pulsed fortnightly dose; the GOG 174 trial (Journal of Clinical Oncology 2011) found pulsed actinomycin D produced more complete responses than weekly methotrexate, though methotrexate remains first choice in many centres for its low toxicity. Treatment continues until hCG is normal and then for three consolidation cycles, and women who develop resistance switch to the other single agent or, if hCG is high, to multi-agent EMA-CO; overall survival in low-risk disease is close to 100 percent whatever the sequence. Second-curettage cures a minority with low hCG, and hysterectomy is an option for women who have completed their families. Because trophoblast expresses PD-L1 almost universally, the anti-PD-L1 antibody avelumab cured eight of fifteen women with single-agent-resistant low-risk disease in the TROPHIMMUN trial (Journal of Clinical Oncology 2020), and pembrolizumab has similar case-series support, so checkpoint inhibitors are now an option to avoid multi-agent chemotherapy. Follow-up hCG monitoring continues for a year and pregnancy is deferred until it is complete; subsequent pregnancies are normal in most cases, with a small risk of a further mole.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Low-risk GTN; Post-molar gestational trophoblastic neoplasia; Persistent trophoblastic disease; Invasive mole and low-risk choriocarcinoma
- Tags: subtype-page; gynaecologic
- Group: gynaecologic
- Burden: The large majority of gestational trophoblastic neoplasia, usually detected by a rising or plateauing hCG after evacuation of a molar pregnancy; cure approaches 100 percent and fertility is preserved.
- Subtypes: Post-molar gestational trophoblastic neoplasia with hCG plateau or rise (commonest presentation); Invasive mole (chorioadenoma destruens); Low-risk gestational choriocarcinoma (FIGO score 6 or below); Low-risk disease with lung metastases (still single-agent); Single-agent-resistant low-risk disease (switch agent, EMA-CO or avelumab); Quiescent gestational trophoblastic disease (low persistent hCG, observation)
- Biomarkers: Serial serum hCG (diagnosis, response, surveillance); FIGO 2000 prognostic score (0 to 6 low risk); Pelvic ultrasound and chest imaging for staging; Pretreatment hCG level (predicts single-agent resistance); Genotyping to confirm gestational origin where uncertain; PD-L1 expression (near universal; checkpoint inhibitor rationale)

## Standard of care

- Diagnosis and staging: Serial hCG after molar evacuation; pelvic Doppler ultrasound and chest X-ray or CT; FIGO scoring; no biopsy needed. ([Ultrasound](https://onco.cc/technologies/ultrasound/), [Tumour markers (CEA, LDH, chromogranin, thyroglobulin)](https://onco.cc/terms/tumour-markers/), [Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)](https://onco.cc/terms/staging-systems/))
- First line: Single-agent methotrexate with folinic acid (eight-day regimen) or pulsed actinomycin D (GOG 174), continued until hCG normalises plus three consolidation cycles. ([Methotrexate](https://onco.cc/drugs/methotrexate/), [Dactinomycin (actinomycin D)](https://onco.cc/drugs/dactinomycin/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/))
- Resistance to first agent: Switch to the alternative single agent if hCG is low; EMA-CO if hCG is high; avelumab or pembrolizumab as chemotherapy-sparing options (TROPHIMMUN). ([Dactinomycin (actinomycin D)](https://onco.cc/drugs/dactinomycin/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Etoposide](https://onco.cc/drugs/etoposide/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Vincristine](https://onco.cc/drugs/vincristine/), [Avelumab](https://onco.cc/drugs/avelumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))
- Surgery: Second uterine evacuation in selected women with low hCG; hysterectomy for women who have completed their families or with uncontrolled bleeding. ([Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/))
- Follow-up: hCG monitoring for twelve months after remission, contraception during follow-up, and hCG after every future pregnancy. ([Tumour markers (CEA, LDH, chromogranin, thyroglobulin)](https://onco.cc/terms/tumour-markers/))

## State of the art

- Cure with fertility preserved is the norm using a single drug.
- hCG monitoring makes it the only cancer routinely diagnosed and followed without imaging or biopsy of the tumour.
- Avelumab offers a chemotherapy-sparing option when the first drug fails.

## Open problems

- Methotrexate and actinomycin D have never been compared head to head with the regimens most centres use.
- Which resistant patients should receive immunotherapy rather than EMA-CO is not settled.
- Overtreatment of quiescent disease with persistently low hCG is a risk.
- Care is centralised in only a few countries.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Gestational_trophoblastic_disease
- GOG 174 (JCO 2011): https://doi.org/10.1200/JCO.2010.30.4386
- TROPHIMMUN (JCO 2020): https://doi.org/10.1200/JCO.20.00803
- Wikipedia: https://en.wikipedia.org/wiki/Gestational_trophoblastic_disease

## Connected records

- cancers: [Gestational trophoblastic neoplasia](https://onco.cc/cancers/gestational-trophoblastic/), [High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk)](https://onco.cc/cancers/high-risk-gtn/), [Placental-site trophoblastic tumour and epithelioid trophoblastic tumour](https://onco.cc/cancers/placental-site-trophoblastic-tumour/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/), [Serum tumour markers: proper use and misuse](https://onco.cc/technologies/serum-tumour-markers/), [Ultrasound](https://onco.cc/technologies/ultrasound/)
- targets: [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Avelumab](https://onco.cc/drugs/avelumab/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Dactinomycin (actinomycin D)](https://onco.cc/drugs/dactinomycin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- terms: [Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)](https://onco.cc/terms/staging-systems/), [Tumour markers (CEA, LDH, chromogranin, thyroglobulin)](https://onco.cc/terms/tumour-markers/)
- key papers: [FIGO staging for gestational trophoblastic neoplasia 2000](https://onco.cc/key-papers/paper-figo-2000-staging-gestational-trophoblastic-neoplasia-ijgo-2002/), [GOG 174: weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia](https://onco.cc/key-papers/paper-gog-174-methotrexate-vs-dactinomycin-low-risk-gtn-jco-2011/), [TROPHIMMUN cohort A: avelumab in gestational trophoblastic tumours resistant to single-agent chemotherapy](https://onco.cc/key-papers/paper-trophimmun-avelumab-chemoresistant-gtn-jco-2020/)

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