High-risk factors in metastatic gestational trophoblastic neoplasia. The patient with gestational trophoblastic neoplasia faces a number of risks; the greatest is the failure of current treatment to bring about remission. Based on a review of past experience, a number of risk factors associated with failure of single-agent chemotherapy were identified, and the subsequent utilization of combination chemotherapy led to an improved outcome. An analysis of more recent experience has identified factors associated with the failure of standard combination chemotherapy, and it is hoped that the development of new treatments will again improve the outcome. This review provides a perspective on known high-risk factors in light of contemporary treatment. 