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Objective: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country., Design: Historical cohort study., Setting: Charing Cross Hospital, United Kingdom., Population: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2)., Methods: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups., Main Outcome Measures: MTX resistance, recurrence rate and survival., Results: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups., Conclusions: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered., Tweetable Abstract: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Introduction: Antecedent term pregnancy is an adverse prognostic factor in Gestational Trophoblastic Disease (GTD). In The Netherlands, patients with post term choriocarcinoma are considered high-risk independent of WHO score. In the present study, we assessed whether post term choriocarcinoma always has to be considered high-risk, requiring first line treatment with combination chemotherapy, or whether a subgroup of patients is distinguishable in which single-agent Methotrexate is a safe alternative., Patients and Methods: The study is a retrospective multicenter cohort study. Patients registered by the Dutch Working Party on Trophoblastic Disease between 1986 and 2004 with choriocarcinoma after a non-molar pregnancy were eligible. Hospital and outpatient records of the patients were reviewed., Results: In total, 68 patients with non-molar choriocarcinoma were registered of whom 44 had an antecedent term pregnancy. Most post term patients (77%) were high-risk according to the WHO staging system. The majority of patients presented with metrorraghia and high hCG levels. Lung and liver metastases were common (respectively 64% and 28%), probably caused by a delay in diagnosis (median interval 16 weeks). Patients were often Methotrexate-resistant (75%). Overall survival was 86% in patients with a post term choriocarcinoma., Conclusions: Although term pregnancy is an adverse prognostic factor in GTD, current survival is comparable to the general survival in high-risk patients. A subgroup of patients in which monotherapy would be sufficient could not be identified. Immediate administration of combination chemotherapy seems justified, even in those few cases when scoring systems would suggest low- or medium-risk disease.