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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis and staging | Serial hCG after molar evacuation; pelvic Doppler ultrasound and chest X-ray or CT; FIGO scoring; no biopsy needed. | not mapped |
| 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. | not mapped |
| 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). | not mapped |
| Surgery | Second uterine evacuation in selected women with low hCG; hysterectomy for women who have completed their families or with uncontrolled bleeding. | not mapped |
| Follow-up | hCG monitoring for twelve months after remission, contraception during follow-up, and hCG after every future pregnancy. | not mapped |