Prophylactic Chemotherapy After Molar Pregnancy Is Unsupported

The controversial practice of prophylactic chemotherapy to prevent gestational trophoblastic neoplasia (GTN) in women with hydatidiform mole, or molar pregnancy, is not recommended, according to the results of a recent intervention review.¹

A molar pregnancy, which is extremely rare, is characterized by a mass that forms from an overgrowth of fetal chorionic tissue in the uterus at the beginning of a pregnancy. Molar pregnancies are categorized as partial or complete. A partial molar pregnancy involves some fetal development along with abnormal placenta, whereas a complete molar pregnancy involves only abnormal placenta with no fetal development. More than 80% of molar pregnancies are benign, but in rare cases the growth persists and develops into GTN.

Researchers identified 3 randomized controlled trials that involved 613 women. One study involving 60 women compared prophylactic dactinomycin with no prophylaxis, and the other 2 studies compared prophylactic methotrexate with no prophylaxis. However, the researchers noted that methodological quality of the latter 2 studies, which involved 420 and 133 women, was poor.

Overall, prophylactic chemotherapy significantly reduced the risk of GTN in women after a molar pregnancy. However, the researchers consider this evidence to be low quality because of the poor methodology of 2 of the studies analyzed. When GTN did occur, the time to diagnosis was longer in women who received prophylactic chemotherapy. In addition, these women required more courses of chemotherapy to “cure” GTN than women who did not receive prophylactic chemotherapy.

Insufficient data made it impossible to determine how prophylactic chemotherapy affected the outcomes for toxicity, overall survival, drug resistence, and reproductive outcomes. However, the authors caution that prophylactic chemotherapy for GTN may increase drug resistance, delay treatment of GTN, and unnecessarily expose women to the toxic adverse effects of chemotherapy.¹

The general risk profile of women who develop GTN after a molar pregnancy is age greater than 40 years, a large increase in the size of the uterus, the presence of large ovarian cysts, and high initial blood levels of beta-human chorionic gonadotropin. Women with a complete molar pregnancy are at greater risk for GTN developing than women with a partial molar pregnancy (1 in 5 vs 1 in 200, respectively). However, almost all cases of GTN are curable, often with preservation of fertility.

Pertinent Points:
- Prophylactic chemotherapy for reducing risk of GTN does not alter the need for careful monitoring and follow-up of women with hydatidiform moles.
- Although the available data show that prophylactic chemotherapy does reduce the risk of the development of GTN, the practice also delays diagnosis and treatment of GTN when it does occur and unnecessarily exposes women in whom GTN never develops to toxic adverse effects.

References:

1. Fu J, Fang F, Xie L, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database System Rev. 2012;10. DOI: 10.1002/14651858.CD007289.pub2.