The Role of Chemotherapy in High-Risk Gestational Trophoblastic Neoplasia - Oncology Central

Multiagent chemotherapy remains the definitive standard for treating high-risk gestational trophoblastic neoplasia, according to a review published in the Expert Review of Anticancer Therapy.

Gestational trophoblastic neoplasia encompasses a group of rare malignant disorders arising from placental trophoblastic tissue. The evaluation highlights that high-risk gestational trophoblastic neoplasia is an exceptionally treatable cancer, achieving cure rates greater than 80–90% when diagnosed quickly, categorized by risk correctly, and treated within specialized reference facilities. Despite this chemosensitivity, delays in diagnosis, inadequate risk stratification, or inappropriate chemotherapy regimens remain the primary determinants of adverse outcomes.

To compile this narrative literature review, researchers searched PubMed/MEDLINE, Scopus, and Web of Science from the inception of these databases through July 2026, alongside a manual check of reference lists and international guidelines. The paper examined risk stratification, frontline and salvage chemotherapy, therapeutic results, causes of resistance to chemotherapy, novel treatments, and how to handle recurring cases.

EMA/CO remains the standard first-line multiagent chemotherapy regimen for most patients with high-risk gestational trophoblastic neoplasia and represents the therapeutic backbone against which alternative regimens are evaluated.

Meanwhile, patients with ultra-high-risk gestational trophoblastic neoplasia, defined as a FIGO score of 13 or greater or extensive visceral disease, require individualized management. To lower the danger of mortality shortly after starting therapy, this strategy features a regimen of low-dose etoposide–cisplatin induction chemotherapy given ahead of full-dose multiagent treatment.

Chemoresistant or relapsed gestational trophoblastic neoplasia remains potentially curable. Tailoring rescue therapy based on a patient’s prior chemotherapy history, tumor spread, and overall condition is essential, with protocols like EP/EMA and TP/TE serving crucial functions. Furthermore, immune checkpoint inhibitors, particularly pembrolizumab, have emerged as highly effective therapeutic options for multidrug-resistant or relapsed disease and are reshaping the salvage-treatment landscape.

The authors point out that keeping treatment concentrated in expert reference centers is vital for maximizing survival and therapeutic success, as it enables precise risk evaluation, uniform chemotherapy protocols, rapid detection of resistance, and prompt access to rescue options. Looking ahead, future advances in molecular diagnostics, predictive biomarkers, targeted therapies, and immunotherapy, together with continued centralization of care, have the potential to further personalize treatment, reduce toxicity, and improve outcomes.