High-risk gestational trophoblastic neoplasia in a middle-income setting:a retrospective review of management and outcomes at a single tertiaryinstitution in South Africa

Abstract

Background: In South Africa, the incidence of high-risk gestational trophoblastic neoplasia (GTN) and the impact of chemotherapy outcomes are largely unknown. This study aimed to evaluate treatment outcomes and identify independent prognostic factors associated with chemotherapy failure in women with high-risk GTN treated at a single tertiary institution in South Africa.

Methods: This retrospective descriptive study reviewed all women with high-risk GTN managed at Groote Schuur Hospital (GSH), Cape Town, from January 2008 to December 2022. Clinical characteristics, treatment regimens, and outcomes were analysed. Univariate logistic regression was used to assess factors associated with mortality.

Results: Of the 95 women treated for GTN during the study period, 34 met the inclusion criteria for high-risk disease. The median age was 33 years, and 35.3% had ultra-high-risk scores (≥ 12). Most patients (76.5%) received EMA/CO (etoposide, methotrexate, and actinomycin D alternating weekly with cyclophosphamide and vincristine) as first-line chemotherapy, with a complete sustained remission rate of 88.2%. Mortality occurred in 11.8% of patients (two early and two late deaths), with ultra-high-risk disease accounting for 50% of all deaths. Risk factors associated with mortality included non-molar antecedent pregnancy, high metastatic burden, stage IV disease, and World Health Organization (WHO) scores ≥ 12. Paclitaxel and etoposide alternating bi-weekly with paclitaxel and cisplatin (TE/TP) was used in select patients, with favourable remission rates and manageable toxicity. The study noted delays in diagnosis and treatment initiation in over one-third of patients, likely due to socio-economic barriers and health system limitations.

Conclusion: High-risk GTN can be effectively treated in a resource-limited setting, with remission rates comparable to international standards. However, early deaths and treatment-related toxicity remain concerning. Identifying patients at risk for poor outcomes – particularly those with ultra-high-risk disease – can guide induction regimens and support tailored management strategies. This is our institution’s first analysis of high-risk GTN, focusing specifically on treatment patterns, remission, and mortality among women with high-risk GTN at a tertiary referral centre in South Africa, highlighting the need for improved diagnostic timelines and expanded treatment capacity.