The role of chemotherapy in high-risk gestational trophoblastic neoplasia.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) comprises a group of rare malignant disorders arising from placental trophoblastic tissue. Despite the remarkable chemosensitivity of high-risk GTN, delays in diagnosis, inadequate risk stratification, or inappropriate chemotherapy regimens remain the primary determinants of adverse outcomes. Understanding the role of chemotherapy is essential to ensure optimal management, maximize cure rates, and ultimately eliminate preventable mortality associated with this disease. AREAS COVERED: A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, and Web of Science, from database inception through July 2026, supplemented by manual review of reference lists and international guidelines. Study selection was based on clinical relevance, methodological rigor, and contribution to the understanding of chemotherapy strategies in high-risk disease. The evidence was qualitatively synthesized, focusing on risk stratification, first-line and salvage chemotherapy, treatment outcomes, mechanisms of chemoresistance, emerging therapies, and the management of relapsed disease. EXPERT OPINION: Although multiagent chemotherapy remains the cornerstone of treatment, 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.