Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide

Abstract

Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.

Keywords: Gestational trophoblastic neoplasia, Chemotherapy, Chorionic gonadotropin, Invasive mole, Choriocarcinoma, Placental site trophoblastic tumor, Epithelioid trophoblastic tumor

Core tip: Gestational trophoblastic neoplasia is a cancer that originates from placental tissue, with potential for invasion and widespread metastasis. It secretes human chorionic gonadotrophin, which serves as a highly useful biomarker that contributes to the diagnosis, monitoring of therapeutic response, subsequent early detection of relapse and assessment of cure. Once the diagnosis is made, staging and International Federation of Gynecology and Obstetrics/World Health Organization prognostic risk score should be obtained, to initiate the treatment of choice – chemotherapy, which allows high cure rates, especially if the treatment occurs in Reference Centers, which has specialized staff in the treatment of this neoplasm.