Current chemotherapeutic options for the treatment of gestational trophoblastic disease

ABSTRACT

Introduction

Gestational trophoblastic neoplasia (GTN) is a rare tumor that arises from trophoblastic tissues with high remission rates after chemotherapy treatment. GTN can develop from any gestational events, such as miscarriage, ectopic pregnancy, and preterm/term pregnancy, but is more frequent after hydatidiform mole. The sensitivity of this tumor to chemotherapy and the presence of an exceptional tumor marker allow high remission rates, especially when patients are treated in referral centers.

Areas covered

Observational, retrospective, prospective, systematic reviews, and meta-analysis studies focusing on GTN treatment. We searched PubMed, Medline, and the Library of Congress from January 1965 to May 2022.

Expert opinion

Early GTN diagnosis allows low-toxic and highly effective treatment. Even multimetastatic disease has high rates of remission with multiagent regimen chemotherapy. Surgery is reserved for uterine disease in patients who have completed childbearing, in cases of chemoresistance to multiagent regimens or in the rare cases of placental site trophoblastic tumor or epithelioid trophoblastic tumor. While resistance is managed by salvage chemotherapy, cases with limited clinical response to sequential regimens have been successfully treated with immunotherapy.

KEYWORDS:

• Gestational trophoblastic neoplasia
• gestational trophoblastic disease
• chemotherapy
• choriocarcinoma
• human chorionic gonadotropin

Article highlights

• The gestational trophoblastic neoplasia diagnosis is essentially hormonal and biochemical, represented by plateau or elevation of human chorionic gonadotropin.

• Gestational trophoblastic neoplasia treatment is guided by assessment of anatomic staging associated with prognostic risk factors, and clinicians should use the FIGO/WHO 2000 scoring system to predict the potential for development of first-line single-agent chemotherapy resistance.

• Low-risk gestational trophoblastic neoplasia should be treated with single-agent chemotherapy, in first (Methotrexate) or second line (Actinomycin-D).

• High-risk gestational trophoblastic neoplasia does not respond to single-agent chemotherapy and should be treated with a multiagent regimen.

• Advanced disease should receive low-dose induction chemotherapy with etoposide and cisplatin, before starting treatment with a multiagent regimen to reduce early deaths from tumor hemorrhage.

• Etoposide–cisplatin low-dose induction is indicated in the following cases: gestational trophoblastic neoplasia with a FIGO score ≥13 and/or patients with a higher number of metastases (more than six metastases) and very high human chorionic gonadotropin (average >700,000–1000,000 IU/L).

• Placental site trophoblastic tumor and epithelioid trophoblastic tumor should be treated with surgery coupled with multiagent chemotherapy in cases with metastatic disease and >48 months from an antecedent pregnancy.

• New pregnancy is allowed 12 months after remission.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2022.2150075

Additional information

Funding

AB was supported by the National Council for Scientific and Technological Development-CNPq (311862/2020-9) and Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro-FAPERJ (E-26/201.166/2022). KME, NH, and RSB were supported by Donald P. Goldstein MD Trophoblastic Tumor Registry Endowment, the Dyett Family Trophoblastic Disease Research and Registry Endowment, and Keith Higgins and the Andrea S. Higgins Research Fund. The funding agencies had no direct role in the generation of the data or the manuscript.