Management of Chemoresistant and Quiescent Gestational Trophoblastic Disease

Abstract

Gestational trophoblastic neoplasia (GTN) is highly chemosensitive and has a high cure rate. Since the introduction of chemotherapy, reliable measurement of human chorionic gonadotropin (hCG) levels, and individualised risk-based therapy into the management of GTN, almost all low-risk and more than 80 % of high-risk GTN cases are curable. However, approximately 25 % of high-risk GTN developed resistance to chemotherapy or relapsed after completion of initial therapy, which often necessitate salvage combination chemotherapy. On the other end of the spectrum, a proportion of patients with gestational trophoblastic disease (GTD) have persistently low levels of hCG, without clinical or radiological evidence of disease, a condition called quiescent GTD. Recently, measurement of hyperglycosylated hCG has been proposed for the management of patients with quiescent GTD. Although representing a small proportion of GTD cases, the management of patients with chemoresistant and quiescent GTD often poses challenges to medical practitioners.

Diagnosis, classification and treatment of gestational trophoblastic neoplasia

“…In contrast, a diagnosis of recurrence is made when there are two elevations of hCG concentrations in the absence of pregnancy after a normal hCG result 40 . Both conditions are challenging in the treatment of GTN.…”

“…The rate of complete response to this regimen is higher among patients that develop resistance (81.8%) than in those with disease recurrence (42.9%), and the most common side effects are myelosuppression, nausea, Table 4. Salvage chemotherapy for resistant or relapsed gestational trophoblastic neoplasia 40 vomiting and hepatotoxicity 46 . With divergent results, Powles et al 47 found an overall 5-year survival of 93% for patients with recurrent disease and 43% for those with chemoresistant disease.…”

Expression patterns of maspin and mutant p53 are associated with the development of gestational trophoblastic neoplasia

“…HMs occur in ~1:600 pregnancies in the United Kingdom (1), with even higher rates in the Middle East, Latin America, Africa and the Far East (2–5). The majority of HMs will spontaneously regress following suction evacuation; however, 8–30% of HMs persist after evacuation and develop into gestational trophoblastic neoplasia (GTN), requiring chemotherapy (6). …”

“…Since the introduction of chemotherapy, reliable measurement of serum β human chorionic gonadotropin (β-hCG) levels and individualized risk-based therapy into the management of GTN, the majority of low-risk and 80% of high-risk GTN cases are curable (6). However, 15–25% of high-risk GTNs develop resistance to chemotherapy, or relapse following the completion of initial therapy, necessitating salvage combination chemotherapy (7).…”

“…At the opposite end of the spectrum, a proportion of patients with GTD have persistently low levels of β-hCG without clinical or radiological evidence of disease, a condition called quiescent GTD. While there is a growing understanding of the molecular biology of GTD, the precise molecular signaling pathways underlying the development of GTD require further exploration (6,8,9). More tumor markers to predict the development of GTN from GTD are required.…”