Gestational Trophoblastic Neoplasia Treatment & Management

Updated: Apr 08, 2021
  • Author: Enrique Hernandez, MD, FACOG, FACS; Chief Editor: Leslie M Randall, MD, MAS, FACS  more...
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Approach Considerations

In September 2013, the European Society of Medical Oncology issued clinical practice guidelines for the diagnosis and treatment of gestational trophoblastic disease. Recommendations include the following [74, 50] :

  • Management of GTN requires pathology review, centralization of care, and monitoring of human chorionic gonadotropin (hCG)

  • After staging with the FIGO scoring system, treatment may include either single-agent methotrexate or single-agent actinomycin D for low-risk disease or multiagent chemotherapy for patients with high-risk disease

  • Low-risk disease requires 6 weeks of maintenance therapy after normalization of hCG, while high-risk disease with liver or brain metastases requires 8 weeks of maintenance therapy

  • In patients with ultra-high-risk GTN, induction with low-dose etoposide and cisplatin may reduce the risk of early mortality

  • Management of PSTT/epithelioid trophoblastic tumor (PSTT/ETT) varies according to disease stage and risk factors for poor outcome, which include the interval from last known pregnancy; hysterectomy with pelvic node sampling is recommended for patients presenting with stage I disease within 4 years of their last known pregnancy, while those presenting later or with metastatic disease may be treated with multi-agent and subsequent high-dose chemotherapy


Medical Care

Patients with gestational trophoblastic disease (GTD) do not require medical therapy. Because 20% of patients with hydatidiform mole develop malignant disease, such as persistent hydatidiform mole with or without metastasis, some have suggested the use of a prophylactic dose of methotrexate in noncompliant patients. [75, 76] However, observing patients with weekly serum hCG levels is preferable, and only patients with rising or plateauing titers, as occurs in patients with gestational trophoblastic neoplasia (GTN), should be treated with chemotherapy. [4]

Low-risk GTN (WHO score < 7)

Patients with low-risk GTN are treated with single-agent chemotherapy. [6, 7, 8, 9, 10, 11, 12] Many in the United States prefer methotrexate. However, actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. Six weeks of maintenance chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the patient receiving methotrexate for nonmetastatic or metastatic low-risk GTN develops rising or plateauing serum hCG levels.

A randomized clinical trial comparing 30 mg/m2 methotrexate given weekly to patients with low-risk GTN versus 1.25 mg/m2 of actinomycin D given every other week showed a higher complete response rate with actinomycin D. [77]  The difference was most marked among patients with a WHO score of 5-6. A subsequent Gynecologic Oncology Group study compared pulse actinomycin D (1.25 mg/m2) to a multi-day (5-day or 8-day with folinic acid) methotrexate regimen. The study was closed due to a low accrual rate. Of the 57 patients entered, the complete response rate for methotrexate was 88%, and it was 79% for actinomycin D. This difference was not statistically significant. However, owing to the small number of patients, the study may have been underpowered. [78]

High-risk GTN (WHO score 7 or higher)

Patients with high-risk GTN have good prognosis if treated aggressively as follows:

  • These patients are treated with a combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin) administered in the second week. [13, 14, 15, 16] This is known as the EMA-CO regimen.

  • Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second week. This is known as the EMA-EP regimen. [17] Some reserve the EMA-EP regimen for patients in whom EMA-CO fails.

  • At least 6 weeks of maintenance of EMA-CO or EMA-EP are administered after a normal serum hCG level.

  • Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with chemotherapy. [19, 20, 21] Corticosteroids (dexamethasone) with systemic effect are administered to reduce brain edema. This is a common approach in the United States.

  • Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross Hospital in the United Kingdom and has been reported by physicians from Duke University in North Carolina. [22] At Charing Cross, neurosurgery is followed by moderate- and high-dose intravenous methotrexate and intrathecal methotrexate. However, intrathecal methotrexate is not routinely used by others. A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at doses of methotrexate >600 mg/m2 given intravenously to patients with brain metastases. [22]

  • In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-EP regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid (15 mg every 12 hours), 12 doses (15 mg every 6 hours) are given starting 24 hours after the initiation of methotrexate infusion. Patients with liver metastasis are considered for liver irradiation (2000 cGy). [18]

  • Patients at high risk of early death (WHO score >12, large disease burden, major bleeding) are treated with low-dose induction etoposide/cisplatin (EP) consisting of 100 mg/m2 of etoposide and 20 mg/m2 of cisplatin on days 1 and 2, repeated weekly for 1-2 cycles before commencing EMA/CO. [50]

Stage IV GTN

Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon.

After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease.


A gynecologic oncologist experienced in managing GTN should be consulted.


Patients with resistant disease may benefit from consultation at a regional trophoblastic disease center.

Diet and activity

There are no dietary and activity restrictions.


Surgical Care

Note the following:

  • A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the total number of chemotherapy cycles needed to achieve remission. [26, 27]

  • Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. [2]

  • A repeat D&C in the presence of persistent tissue on pelvic ultrasonography may reduce the number of chemotherapy cycles needed to achieve remission. [28]

  • Craniotomy may be needed to control bleeding and provide decompression. [15, 22]

  • Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission. [23, 24, 25]