Current management of gestational trophoblastic diseases

Abstract

Objectives: This review was undertaken to describe current understanding of the natural history of molar pregnancy and persistent gestational trophoblastic neoplasia (GTN) as well as recent advances in their management.

Materials and methods: Recent literature related to molar pregnancy and GTN was thoroughly analyzed to provide a comprehensive review of the current knowledge of their pathogenesis and treatment.

Results: Studies in patients with familial recurrent molar pregnancy indicate that dysregulation of parentally imprinted genes is important in the pathogenesis of complete hydatidiform mole (CHM). CHM is now being diagnosed earlier in pregnancy in the first trimester changing the clinical presentation and making the histologic appearance more similar to partial hydatidiform mole (PHM) and hydropic abortion. While the classic presenting symptoms of CHM are less frequent, the risk of developing GTN remains unchanged. Flow cytometry and immunostaining for maternally-expressed genes are helpful in distinguishing early CHM from PHM or hydropic abortion. Patients with molar pregnancy have a low risk of developing persistent GTN after achieving even one non-detectable hCG level (hCG <5 mIU/ml). Patients with persistent low levels of hCG should undergo tests to determine if the hCG is real or phantom. If the hCG is real, then further tests should determine what percentage of the total hCG is hyperglycosylated hCG and free beta subunit to establish a proper diagnosis and institute appropriate management. Patients with non-metastatic GTN have a high remission rate with many different single-agent regimens including methotrexate and actinomycin D. Patients with high-risk metastatic GTN require aggressive combination chemotherapy in conjunction with surgery and radiation therapy to attain remission. After achieving remission, patients can generally expect normal reproduction in the future.

Conclusion: Our understanding of the natural history and management of molar pregnancy and GTN has advanced considerably in recent years. While most patients can anticipate a high cure rate, efforts are still necessary to develop effective new second-line therapies for patients with drug-resistant disease.