Prophylactic (preventive) chemotherapy for hydatidiform mole (molar pregnancy) to prevent cancerous growth later

Wang Q, Fu J, Hu L, Fang F, Xie L, Chen H, He F, Wu T, Lawrie TA


A molar pregnancy (hydatidiform mole) develops following an abnormal process of conception, whereby placental tissue overgrows inside the womb (uterus). Molar pregnancies are classified as complete (CM) or partial (PM) based on their appearance (gross and microscopic), and their chromosome pattern. When present, moles are usually suspected at the early pregnancy scan and women often present with bleeding, similar to a miscarriage. The molar tissue is removed by evacuation of retained products of conception (ERPC), also known as dilatation and curettage (D&C) and women generally make a full recovery. However, some women go on to develop a cancer in the womb (about 1 in every 5 women with a CM and 1 in 200 with a PM). Women are generally at a higher risk of getting this cancer, which is known as gestational trophoblastic neoplasia (GTN), if they are over 40 years old, have a large increase in the size of the womb, have large cysts in the ovaries or have high initial levels of β-human chorionic gonadotrophin (hCG) (the pregnancy hormone) in their blood. Although treatment of the cancer with chemotherapy (anti-cancer drugs) is almost always effective, it has been suggested that routinely giving women anti-cancer drugs (P-Chem) before or after the removal the molar tissue may reduce the risk of the cancerous tissue developing.

The aim of the review

By doing this review, we tried to assess the benefits and risks of giving anti-cancer drugs (P-Chem) to women with molar pregnancies, before or after ERPC.

What are the main findings?

We found three randomised studies (randomised controlled trials (RCTs) where people are allocated at random i.e. by chance alone) involving a total of 613 women. Two studies tested methotrexate in all women with a CM and one study tested dactinomycin in women with a CM who were at a high risk of getting GTN. The two methotrexate studies are older studies that used relatively poor research methods, therefore their findings cannot be relied upon. Overall the review findings suggest that P-Chem reduces the number of women developing cancer after molar pregnancy; however, this is probably only true for women with high-risk moles (i.e. CM). In addition, P-Chem might make the time to diagnose the cancer longer and might increase the number of anti-cancer treatments needed to cure the cancer if it develops. We were unable to assess the short- and long-term side-effects of P-Chem in this review because there were not enough available data; however, we are concerned that the five- and eight-day courses of P-Chem used by researchers in these studies are too toxic to be given to women routinely.

Quality of the evidence

We consider this evidence to be of a low to very low quality. This conclusion is based on our assessment that two of the included studies were of poor methodological quality and at a high risk of bias; the third study was of a good quality but consisted of only 60 participants.

What are the conclusions?

Currently there is insufficient evidence to support giving anti-cancer drugs to women with molar pregnancies. However, GTN is almost always cured with modern care and P-Chem for molar pregnancy would only reduce the risk of needing full-scale chemotherapy, but would not remove that risk. In addition, it would not change the need for careful monitoring and follow-up of women with hydatidiform moles.

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