Treatment of High-Risk Gestational Trophoblastic Tumors JASON D. WRIGHT, MD, DAVID G. MUTCH, MD Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine Introduction Over the last century, remarkable advances have been made in our understanding of ges- tational trophoblastic neoplasms. In 1895, Marchand first suggested that these tumors were derived from trophoblastic cells. Then, in 1956, Li et al demonstrated the sensitivity of the tumors to chemotherapy. 1 Since Li’s landmark discovery, the survival rates for gestational trophoblastic tumors have stead- ily increased. Cure rates for patients with metastatic trophoblastic tumors now exceed 90%. 2 While improvements have been made, a subset of patients, primarily those with high-risk tumors, will still succumb to their disease. The optimal management of these high-risk patients depends on prompt diagnosis, proper treatment, and referral to individuals or centers with expertise in the management of such tumors. 3 Classification Several systems are currently in use to clas- sify gestational trophoblastic tumors. Early investigators recognized several clinical factors that appeared to portend a worse prognosis. 4 Based upon these factors, a clinical classification system was devel- oped. Patients with any of the following risk factors were considered to have high-risk trophoblastic disease: brain or liver metasta- ses, pretreatment serum hCG > 40,000 mIU/mL, unsuccessful prior chemotherapy, antecedent term pregnancy or greater than 4 months between the antecedent gestation and diagnosis (Table 1). 5–7 Based upon this system, patients can be classified into three groups: nonmetastatic, low-risk metastatic, and high-risk metastatic. It was demon- strated that patients with low-risk metastatic disease had a survival rate of 98%, while pa- tients with high-risk metastatic disease had a survival rate of only 47%. 5 An additive ef- fect has been demonstrated in which patients with a greater number of adverse criteria have a worse prognosis. 8 Bagshawe devised a scoring system that used several prognostic factors to calculate a weighted score. 9 The World Health Organi- zation (WHO) later modified and adopted this system (Table 2). Based upon the WHO score, patients are classified into three cat- Correspondence: Jason D. Wright, MD, Washington University School of Medicine, 4911 Barnes Hospital Plaza, Box 8064, St. Louis, MO 63110-1094. E-mail: wrightj@msnotes.wustl.edu CLINICAL OBSTETRICS AND GYNECOLOGY Volume 46, Number 3, 593–606 © 2003, Lippincott Williams & Wilkins, Inc. CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 46 / NUMBER 3 / SEPTEMBER 2003 593