Treatments for Gestational Trophoblastic Disease

Laura Kenny; Michael J Seckl

Disclosures

Expert Rev of Obstet Gynecol. 2010;5(2):215-225. 

In This Article

Abstract and Introduction

Abstract

Gestational trophoblastic disease (GTD) is a relatively rare but important group of benign and malignant disorders that affect women of child-bearing potential. Most cases are now diagnosed earlier than previously owing to advances in our knowledge of the disease and accuracy of ultrasonography, combined with the high analytical sensitivity of human chorionic gonadotrophin assays, although occasionally patients with metastases present at a late stage with life-threatening complications. Early diagnosis and referral to a specialist center for further management is vital so that patients can receive the optimal standard of care. Patients can be grouped into high- and low-risk categories using well-established prognostic scoring systems, enabling the minimum appropriate treatment to be recommended. Chemotherapy regimens for the disease are now well established, so that for the vast majority, GTD is a curable condition, and patients can be reassured that fertility is normally preserved. Regular follow-up by human chorionic gonadotrophin measurement following treatment is important for the detection of early relapse. Regimens for relapsed disease are usually successful, but need to be improved for the infrequent cases that develop multiple drug resistance. In this article the subtypes of GTD, rationale for treatment, surgery and drugs used in the condition are discussed.

Introduction

Gestational trophoblastic disease (GTD) spans a spectrum from two premalignant conditions: partial and complete hydatidiform moles, to three malignant tumors, namely: invasive mole, gestational choriocarcinoma and placental-site trophoblastic tumor (PSTT);[1] the latter three are sometimes referred to as gestational trophoblastic neoplasia.

Gestational trophoblastic tissue forms from the peripheral cells of the blastocyst a few days after conception. The tissue is divided into two layers: the outer syncytiotrophoblast composed of large mutinucelated cells and an inner layer of mononucleated cells that migrate out and fuse to form the cytotrophoblast. The syncytiotrophoblast subsequently aggressively invades the endometrium, generating an intimate connection between the fetus and the mother, known as the placenta. Normally, the growth of trophoblastic tissue is tightly regulated by as yet undefined mechanisms that prevent the development of distant metastases. Malignant GTD occurs when these controling mechanisms fail, which may result in invasion of trophoblastic tissue through the myometrium, permitting hematogenous spread and tumor emboli to form.

The revised International Federation of Gynecology and Obstetrics (FIGO) classification of GTD was developed in 2000 after many years of discussion between international experts in the field, and is the most appropriate method for categorizing the disease into high- and low-risk categories.[2] Successful management of GTD now means that for the vast majority of patients the disease is curable. This has been largely dependent on a combination of centralized care leading to accumulated knowledge about the biology, pathology and natural history of the disease. Fertility can be preserved and normal outcomes can be expected in subsequent pregnancies in most cases.[3] The tumors are extremely chemosensitive; the intensity of treatment is guided by the prognostic category (which comprises of human chorionic gonadotrophin [hCG] level, maternal age, length of time elapsed since previous pregnancy, size of uterine lesion, sites of metastases and number of previous chemotherapy regimens) at the time of referral. The high sensitivity and specificity of hCG assays allow the success of treatment to be followed accurately, enabling the early detection of treatment failure and relapse.

While GTD is a relatively rare diagnosis, higher incidences (up to one in 300 pregnancies) are seen in certain populations, namely Brazil, the Philippines and in native American Indians. The incidence in countries such as Japan appears to be falling, possibly owing to better data collection and reduced dependency on hospital-based surveys as opposed to national population data, and possibly owing to dietary influences. This article focuses on the Charing Cross Hospital (London, UK) experience. For a comprehensive review of the genetic abnormalities underlying GTD, readers are referred to the paper published by Fisher and Hodges.[4] The various types of hCG assays, subtypes of GTD, diagnosis, management options, and potential complications of the disease and treatment will be discussed.

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