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Gestational Trophoblastic Disease

Gestational trophoblastic disease encompasses four clinicopathologic forms of growth disturbances of the human placenta: 1) hydatidiform mole (complete and partial), 2) invasive mole, 3) choriocarcinoma, and 4) placental-site trophoblastic tumor molar pregnancy, gestational trophoblastic disease, mole, placenta tumor, placenta cancer, hydatiform mole, choriocarcinoma, trophoblastic tumor. The term "gestational trophoblastic tumor'' has been applied collectively to the latter three conditions. The diagnosis and decision to institute treatment of gestational trophoblastic disease are

Hydatidiform Mole

Hydatidiform mole is a pregnancy that is characterized by vesicular swelling of placental villi and, usually, the absence of an intact fetus. There is a microscopic proliferation of the trophoblast (both cytotrophoblast and syncytiotrophoblast) with varying degrees of hyperplasia and dysplasia. The chorionic villi are fluid filled and

Patients with partial moles usually do not present with the classic clinical features of complete moles described above. More than 90% of patients present with symptoms of incomplete or missed abortion, and the diagnosis of partial mole is usually made after histologic review of curettage specimens. The main presenting symptom is vaginal bleeding, occurring in about 75% of patients. Excessive uterine enlargement, pregnancy-induced hypertension, hyperemesis, hyperthyroidism, and theca lutein ovarian cysts develop infrequently. Preevacuation hCG levels are usually not as high as they are in complete moles, exceeding 100,000 mIU/mL in fewer than 10% of patients with partial moles. Ultrasonography may facilitate the early diagnosis of a partial mole by demonstrating focal cystic spaces within the placenta and an increase in the transverse diameter of the gestational sac.

Treatment

When the diagnosis of hydatidiform mole is established, the patient should be carefully evaluated for the presence of associated medical complications and stabilized, after which the most appropriate method of molar evacuation should be determined. The preoperative evaluation should consist of a history and physical examination, complete blood and platelet counts, coagulation profile, serum chemistries, thyroid panel, blood type and crossmatch, serum hCG level, urinalysis, chest X-ray, electrocardiography, and pelvic ultrasonography.

Suction curettage is the preferred method of evacuation of a hydatidiform mole, independent of uterine size, in patients who wish to maintain their fertility. Suction evacuation should be followed by gentle sharp curettage. An oxytocic agent should be infused intravenously near the end of evacuation and continued for several hours to enhance uterine contractibility. Attention to blood and crystalloid replacement should be exercised to decrease the pulmonary complications. Because trophoblastic cells express the CDE (Rh) factor, patients who are D negative should receive D (Rho[D]) immune globulin at the time of evacuation.

Hysterectomy is an alternative to suction curettage if childbearing is complete. The adnexa may be preserved even in

Gestational Trophoblastic Tumors

Gestational trophoblastic tumors include invasive mole, choriocarcinoma, and placental site trophoblastic tumor. If untreated, these tumors can progress, invade, metastasize, and lead to death. The overall cure rate in the treatment of gestational trophoblastic tumors now exceeds 90%. This success is the result of the chemotherapy-sensitive nature of

Classification and Staging

When a gestational trophoblastic tumor has been diagnosed, it is necessary to determine the extent of disease. If the physical examination and chest X-ray are normal, other sites of metastasis are uncommon. Measurement of hCG in

Therapy

Nonmetastatic Tumors

Hysterectomy is used as primary therapy in patients with presumed nonmetastatic trophoblastic tumors who no longer wish to preserve fertility or when the diagnosis is placental-site trophoblastic tumor. Adjuvant single-agent chemotherapy at the time of operation has been assumed to eradicate any occult metastases and reduce the

Single-agent chemotherapy with methotrexate or dactinomycin is the treatment of choice for those patients wishing to preserve their fertility. Several different outpatient chemotherapy protocols have been used, all yielding excellent and fairly comparable remission rates. Methotrexate 0.4 mg/kg (maximum 25 mg) intravenously or intramuscularly daily for 5 days per treatment course has traditionally been the treatment of choice. Alternately, a regimen consisting of

Staging for Gestational Trophoblastic Tumors*
Stage I	Disease is confined to uterus.
Stage IA	Disease is confined to uterus with no risk factors.
Stage IB	Disease is confined to uterus with one risk factor.
Stage IC	Disease is confined to uterus with two risk factors.
Stage II	Gestational trophoblastic tumor extends outside uterus but is limited to genital structures (adnexa, vagina, broad ligament).
Stage IIA	Gestational trophoblastic tumor involves genital structures with no risk factors.
Stage IIB	Gestational trophoblastic tumor extends outside uterus but is limited to genital structures with one risk factor.
Stage IIC	Gestational trophoblastic tumor extends outside uterus but is limited to genital structures with two risk factors.
Stage III	Gestational trophoblastic tumor extends to lungs with or without known genital tract involvement.
Stage IIIA	Gestational trophoblastic tumor extends to lungs with or without genital tract involvement and with no risk factors.
Stage IIIB	Gestational trophoblastic tumor extends to lungs with or without genital tract involvement and with one risk factor.
Stage IIIC	Gestational trophoblastic tumor extends to lungs with or without genital tract involvement and with two risk factors.
Stage IV	Included are all other metastatic sites.
Stage IVA	Included are all other metastatic sites without risk factors.
Stage IVB	Included are all other metastatic sites with one risk factor.
Stage IVC	Included are all other metastatic sites with two risk factors.

*Risk factors affecting staging include the following: 1) serum human chorionic gonadotropin >100,000

Metastatic Tumors

Low-Risk Disease. Single-agent chemotherapy with 5-day dosage schedules of methotrexate or dactinomycin (as described in the "Nonmetastatic Tumors" section) is the treatment for patients with low-risk metastatic tumors. When resistance to sequential single-agent chemotherapy develops, combination chemotherapy, as for high-risk disease, is

Table 16. Who Scoring System Based on Prognostic Factors for Gestational Trophoblastic Tumors*
	Score
Risk Factor	0	1	2	4
Age (y)	#39	>39
Antecedent pregnancy	Hydatidiform mole	Abortion	Term
Pregnancy event to treatment interval (mo)	<4	4-6	7- 12	>12
Human chorionic gonadotropin (IU/L)	<10³	10³-10⁴	10⁴-10⁵	>10⁵
ABO blood groups (female x male)		O x A A x O	B AB
No. of metastases		1-4	4-8	>8
Site of metastases		Spleen Kidney	Gastrointestinal tract Liver	Brain
Largest tumor mass, including uterine (cm)		3-5	>5
Prior chemotherapy			Single drug	Two or more drugs

High-Risk Disease. Patients with high-risk metastatic gestational trophoblastic tumors should be treated more aggressively with initial combination chemotherapy with or without adjuvant radiation therapy or surgery. Because the discovery of etoposide was found to be an effective agent in gestational trophoblastic tumors, all currently acceptable protocols for the treatment of high-risk disease should include this drug, along with methotrexate and dactinomycin. The EMA-CO regimen uses etoposide intravenously on days 1 and 2; a high-dose methotrexate intravenous push

Trophoblastic Disease Surveillance

After completion of chemotherapy, serum quantitative hCG levels should be obtained at 1- to 2-week intervals for 3 months, then at 1-month intervals for 12 months. The risk of recurrence is low after 1 year. Physical examinations are performed at 6- to 12-month intervals, and other examinations such as chest X-rays are performed as indicated. Contraception should be maintained during treatment and for 1 year after the completion of