Intervention Review

Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia

  1. Jing Fu1,
  2. Fang Fang2,
  3. Lingxia Xie2,
  4. Hengxi Chen2,
  5. Fan He3,
  6. Taixiang Wu4,
  7. Lina Hu5,*,
  8. Theresa A Lawrie6

Editorial Group: Cochrane Gynaecological Cancer Group

Published Online: 17 OCT 2012

Assessed as up-to-date: 10 AUG 2012

DOI: 10.1002/14651858.CD007289.pub2

How to Cite

Fu J, Fang F, Xie L, Chen H, He F, Wu T, Hu L, Lawrie TA. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD007289. DOI: 10.1002/14651858.CD007289.pub2.

Author Information

  1. 1

    West China Second University Hospital, Sichuan University, Department of Obstetrics and Gynecology, Chengdu, Sichuan, China

  2. 2

    West China Second University Hospital, West China Women's and Children's Hospital, Department of Obstetrics and Gynecology, Chengdu, Sichuan, China

  3. 3

    West China Hospital, Sichuan University, Chengdu, Sichuan, China

  4. 4

    West China Hospital, Sichuan University, Chinese Clinical Trial Registry, Chinese Ethics Committee of Registering Clinical Trials, Chengdu, Sichuan, China

  5. 5

    The Second Affiliated Hospital of Chongqing Medical University, The Obstetrics and Gynecology Department, Chongqing, China

  6. 6

    Royal United Hospital, Cochrane Gynaecological Cancer Group, Bath, UK

*Lina Hu, The Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Rd, Chongqing, 400010, China.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 OCT 2012




  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約


Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear.


To systematically review the evidence for the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy.

Search methods

We performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and EMBASE (1980 to week 9, 2012). The search strategy was developed using free text and medical subject headings (MESH). We handsearched reference lists of relevant literature to identify additional studies.

Selection criteria

We included randomised controlled trials (RCTs) of P-Chem for HM.

Data collection and analysis

Two review authors independently assessed studies for inclusion in the review and extracted data using a specifically designed data collection form. Meta-analyses were performed by pooling data from individual trials using RevMan 5.1 software.

Main results

We included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality.

P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; RR 0.37; 95% confidence interval (CI) 0.24 to 0.57; I2 = 0%; P < 0.00001), However, owing to the poor quality of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28; 95% CI 0.10 to 0.73; P = 0.01), therefore we consider this evidence to be of a low quality.

The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72; 95% CI 13.19 to 44.24; P = 0.0003) and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10; 95% CI 0.52 to 1.68; P = 0.0002). We consider this evidence to be of a low to very low quality for similar reasons to those listed above.

There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes.

Authors' conclusions

P-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delay treatment of GTN and expose women unnecessarily to toxic side effects, this practice cannot currently be recommended.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約

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

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. 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.

By doing this review, we tried to assess the benefits and risks of giving P-Chem to women with molar pregnancies, before or after ERPC. We found three randomised studies 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 be true for women with high-risk moles. In addition, P-Chem might make the time to diagnosing 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 was 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.

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.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約







Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials(CENTRAL、2012年第2号)、MEDLINE(1946~2012年2月第4週)、EMBASE(1980~2012年第9週)の電子的検索を行った。自由文およびmedical subject headings(MESH)を用いて検索方法をあみ出した。関連する文献の参考文献リストをハンドサーチしその後追加された研究を同定した。




2名のレビューアが別々に本レビューの選択について研究を評価し、特別にデザインしたデータ収集フォームにデータを抽出した。RevMan 5.1ソフトウェアを用いて個々の試験からデータを統合しメタアナリシスを実施した。


統合した結果、総計参加者613名になる3件のRCTを選択した。1件の研究(参加者60名)では、ダクチノマイシン予防投与を予防投与なしと比較し、他の2件の研究(参加者420名および133名)ではメトトレキサート予防投与を予防投与なしと比較していた。すべての参加者はCMと診断されていた。後者2件の研究の方法論的質は良くないと判断した。予防的化学療法により、CM後の女性でのGTN発症リスクが低下した(3件の研究、参加者550名、RR 0.37、95%信頼区間(CI)0.24~0.57、I2 = 0%、P < 0.00001)が、選択した2件の研究の質が良くなかったため、これらの2件の研究を除外して感度分析を実施した。このため、この主要アウトカムのためのデータとして寄与するのは、高リスクの女性を対象とした1件の小規模研究(参加者59名、RR 0.28、95%CI 0.10~0.73、P = 0.01)しか残らないこととなり、本エビデンスの質は低いと判断した。診断までの時間はコントロール群より予防的化学療法群の方が長く[2件の研究、参加者33名、平均差(MD)28.72、95%CI 13.19~44.24、P = 0.0003]、予防的化学療法群の方がその後のGTN治癒のためのクール数を多く必要とした(質の低い1件の研究、参加者14名、MD 1.10、95%CI 0.52~1.68、P = 0.0002)。上記と同様の理由から、本エビデンスの質は低~非常に低いと判断した。毒性、全生存、薬剤耐性、生殖能アウトカムについてのメタアナリシスを実施するには不十分なデータしかなかった。





  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約




監  訳: 大神 英一,2013.2.19

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