All patients with high-risk GTN (stages II–IV) should be treated with primary intensive combination chemotherapy and the selective use of radiation therapy and surgery. Between July 1965 and June 2008, of the 103 patients with high-risk GTN stages II–IV treated at the NETDC, 83 (80.5%) achieved complete remission. Before 1975, when single agent therapy was used primarily to treat patients with stage IV GTN, only 6 of 20 patients (30%) attained complete remission. Since 1975, 17 of 21 patients (80.9%) achieved remission. This improvement in survival resulted from the use of multimodal therapy, including primary combination chemotherapy in conjunction with radiation and surgical treatment. Patients with stage IV disease are at the greatest risk of developing rapidly progressive and unresponsive tumors despite intensive multimodal therapy. They should be referred to centers with special expertise in the management of trophoblastic disease.
The management of resistant hepatic metastasis is particularly difficult (63). If a patient becomes resistant to systemic chemotherapy, hepatic arterial infusion of chemotherapy may induce complete remission in selected cases. Hepatic resection may be required to control acute bleeding or to excise a focus of resistant tumor. New techniques of arterial embolization may reduce the need for surgical intervention.
At the NETDC, cerebral metastases are treated with either whole-brain radiation (3,000 cGy in 10 fractions) or stereotactic radiosurgery in conjunction with combination chemotherapy. Because irradiation may be hemostatic and tumoricidal, the risk of spontaneous cerebral hemorrhage may be lessened by the concurrent use of combination chemotherapy and brain irradiation. Excellent remission rates (86%) were reported in patients with cranial metastases treated with intensive intravenous combination chemotherapy and intrathecal methotrexate (MTX) (64).
Craniotomy Craniotomy may be required to provide acute decompression or to control bleeding. It should be performed to manage life-threatening complications so that the patient ultimately will be cured with chemotherapy. In a study of six patients (65), the use of craniotomy to control bleeding resulted in complete remission in three patients. Infrequently, cerebral metastases that are resistant to chemotherapy may be amenable to local resection (66). Patients with cerebral metastases who achieve sustained remission generally have no residual neurologic deficits.
Patients with stage IV disease should receive follow-up with: 1.
Weekly determination of hCG levels until they are normal for 3 consecutive weeks.
2.
Monthly determination of hCG levels until they are normal for 24 consecutive months.
These patients require prolonged gonadotropin follow-up because they are at increased risk of late recurrence.
An algorithm for the management of persistent GTN is presented in Figure 39.7.
GTN Choriocarcinoma Mole Evacuation and  weekly hCG levels ↓ hCG levels ↑ or plateau of hCG levels Careful follow-up and contraception Distant metastasis Uterine disease Pelvic metastasis Lung metastasis Stage IVStage I Stage II Stage III Combination chemotherapy ± surgery ± RT Single drug chemotherapy or hysterectomy Calculate risk Low High ResistantFollow-up Metastatic work-up Figure 39.7 Management of gestational trophoblastic tumor. GTN, gestational trophoblastic neoplasia; hCG, human chorionic gonadotropin; RT, radiotherapy. (From Berkowitz RS, Goldstein DP. Gestational trophoblastic neoplasia. In: Berek JS, Hacker NF. Berek and Hacker’s Gynecologic Oncology, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010;607, with permission.) 1473