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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.
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.
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.
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
Serial hCG after molar evacuation; pelvic Doppler ultrasound and chest X-ray or CT; FIGO scoring; no biopsy needed.
Single-agent methotrexate with folinic acid (eight-day regimen) or pulsed actinomycin D (GOG 174), continued until hCG normalises plus three consolidation cycles.
Switch to the alternative single agent if hCG is low; EMA-CO if hCG is high; avelumab or pembrolizumab as chemotherapy-sparing options (TROPHIMMUN).
Second uterine evacuation in selected women with low hCG; hysterectomy for women who have completed their families or with uncontrolled bleeding.
hCG monitoring for twelve months after remission, contraception during follow-up, and hCG after every future pregnancy.
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Avelumab is a chemotherapy-sparing option for single-agent-resistant gestational trophoblastic neoplasia, particularly where the alternative is combination chemotherapy.
Pulsed dactinomycin is at least as good as weekly methotrexate for low-risk GTN, but many centres still prefer the multi-day methotrexate-folinic acid schedule, which was not tested here; overall cure approaches 100 percent whichever drug comes first.
Whether a woman with GTN receives one drug or several rests on this scoring system, which is why OnCo has separate low-risk and high-risk pages.
Query for this cancer: (TITLE:"Low-risk gestational trophoblastic neoplasia" OR ABSTRACT:"Low-risk gestational trophoblastic neoplasia" OR TITLE:"FIGO score 0 to 6" OR ABSTRACT:"FIGO score 0 to 6" OR TITLE:"Low-risk GTN" OR ABSTRACT:"Low-risk GTN" OR TITLE:"Post-molar gestational trophoblastic neoplasia" OR ABSTRACT:"Post-molar gestational trophoblastic neoplasia" OR TITLE:"Persistent trophoblastic disease" OR ABSTRACT:"Persistent trophoblastic disease" OR TITLE:"Invasive mole and low-risk choriocarcinoma" OR ABSTRACT:"Invasive mole and low-risk choriocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Fatal if given intrathecally: label all syringes.
Reduce to 75% for CrCl 15-50.
High-dose methotrexate requires normal renal function, hydration, urine alkalinisation and leucovorin rescue with level monitoring.
See all on the product pages:AvelumabCyclophosphamideDactinomycin (actinomycin D)EtoposideMethotrexatePembrolizumabVincristine·Printable cards in the navigator
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