State-of-the-Art Workup and Initial Management of Newly Diagnosed Molar Pregnancy and Postmolar Gestational Trophoblastic Neoplasia

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Gestational trophoblastic disease refers to a series of interrelated tumors arising from the placenta, including benign molar pregnancies as well as the malignant conditions termed gestational trophoblastic neoplasia (GTN). GTN most commonly follows a molar pregnancy but may develop after any gestation. The wide availability of first trimester ultrasound and serum human chorionic gonadotropin (hCG) measurement has changed the presentation of molar pregnancy in recent decades from a second trimester to a first trimester disease, such that most patients have few symptoms at diagnosis. With identification of molar pregnancy at earlier gestations, accurate diagnosis increasingly relies on expert histopathology coupled with ancillary molecular and genetic techniques. However, earlier diagnosis has not changed the risk of postmolar GTN. Although most molar pregnancies are treated with dilation and curettage, hysterectomy may be appropriate in select cases when future fertility is not desired. After treatment of molar pregnancy, close surveillance with serial hCG monitoring is essential to diagnose GTN and identify the need for chemotherapy. Physicians following hCG levels should understand the performance characteristics of the test, including common causes of false-positive and false-negative results. After a diagnosis of postmolar GTN is made, selection of single-agent or multiagent chemotherapy depends on accurate assignment of the clinical stage and risk stratification by the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system. Surgical treatment of postmolar low-risk GTN, including both second uterine curettage and hysterectomy, may decrease subsequent need for or duration of chemotherapy. Cure rates for postmolar low-risk GTN approach 100%, and subsequent pregnancy outcomes for patients reflect those of the general population.

Submitted July 1, 2019; accepted for publication September 30, 2019.Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Research at the New England Trophoblastic Disease Center is supported by the Donald P. Goldstein, MD, Trophoblastic Tumor Registry Endowment and the Dyett Family Trophoblastic Disease Research and Registry Endowment.Correspondence: Ross S. Berkowitz, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Email: rberkowitz@partners.org
  • 1.

    Lurain JR. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol 2011;204:11–18.

  • 2.

    Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;376:717–729.

  • 3.

    Ngan HYS, Seckl MJ, Berkowitz RS, . Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet 2018;143(Suppl 2):79–85.

  • 4.

    Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N Engl J Med 2009;360:1639–1645.

  • 5.

    Szulman AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol 1978;131:665–671.

  • 6.

    Nguyen NMP, Khawajkie Y, Mechtouf N, . The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients. Mod Pathol 2018;31:1116–1130.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Moglabey YB, Kircheisen R, Seoud M, . Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum Mol Genet 1999;8:667–671.

  • 8.

    Soto-Wright V, Bernstein M, Goldstein DP, Berkowitz RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995;86:775–779.

  • 9.

    Hou JL, Wan XR, Xiang Y, . Changes of clinical features in hydatidiform mole: analysis of 113 cases. J Reprod Med 2008;53:629–633.

  • 10.

    Braga A, Moraes V, Maestá I, . Changing trends in the clinical presentation and management of complete hydatidiform mole among Brazilian women. Int J Gynecol Cancer 2016;26:984–990.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Sun SY, Melamed A, Goldstein DP, . Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia? Gynecol Oncol 2015;138:46–49.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Mosher R, Goldstein DP, Berkowitz R, . Complete hydatidiform mole: comparison of clinicopathologic features, current and past. J Reprod Med 1998;43:21–27.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Berkowitz RS, Goldstein DP, Bernstein MR. Natural history of partial molar pregnancy. Obstet Gynecol 1985;66:677–681.

  • 14.

    Joneborg U, Marions L. Current clinical features of complete and partial hydatidiform mole in Sweden. J Reprod Med 2014;59:51–55.

  • 15.

    Sun SY, Melamed A, Joseph NT, . Clinical presentation of complete hydatidiform mole and partial hydatidiform mole at a regional trophoblastic disease center in the United States over the past 2 decades. Int J Gynecol Cancer 2016;26:367–370.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Fowler DJ, Lindsay I, Seckl MJ, . Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol 2006;27:56–60.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Johns J, Greenwold N, Buckley S, . A prospective study of ultrasound screening for molar pregnancies in missed miscarriages. Ultrasound Obstet Gynecol 2005;25:493–497.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Benson CB, Genest DR, Bernstein MR, . Sonographic appearance of first trimester complete hydatidiform moles. Ultrasound Obstet Gynecol 2000;16:188–191.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Fine C, Bundy AL, Berkowitz RS, . Sonographic diagnosis of partial hydatidiform mole. Obstet Gynecol 1989;73:414–418.

  • 20.

    Seckin KD, Baser E, Yeral I, . The impact of ultrasonographic lesion size and initial human chorionic gonadotropin values on treatment success in cases with complete hydatidiform mole. Eur Rev Med Pharmacol Sci 2013;17:3381–3384.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Padrón L, Rezende Filho J, Amim Junior J, . Manual compared with electric vacuum aspiration for treatment of molar pregnancy. Obstet Gynecol 2018;131:652–659.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Elias KM, Goldstein DP, Berkowitz RS. Complete hydatidiform mole in women older than age 50. J Reprod Med 2010;55:208–212.

  • 23.

    Elias KM, Shoni M, Bernstein M, . Complete hydatidiform mole in women aged 40 to 49 years. J Reprod Med 2012;57:254–258.

  • 24.

    Kim DS, Moon H, Kim KT, . Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Obstet Gynecol 1986;67:690–694.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Limpongsanurak S. Prophylactic actinomycin D for high-risk complete hydatidiform mole. J Reprod Med 2001;46:110–116.

  • 26.

    Wang Q, Fu J, Hu L, . Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2017;9:CD007289.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Sturgeon CM, Berger P, Bidart JM, . Differences in recognition of the 1st WHO international reference reagents for hCG-related isoforms by diagnostic immunoassays for human chorionic gonadotropin. Clin Chem 2009;55:1484–1491.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Harvey RA, Mitchell HD, Stenman UH, . Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors. J Reprod Med 2010;55:285–295.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Cole LA, Shahabi S, Butler SA, . Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases. Clin Chem 2001;47:308–315.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Levavi H, Neri A, Bar J, . “Hook effect” in complete hydatidiform molar pregnancy: a falsely low level of beta-HCG. Obstet Gynecol 1993; 82(4 Pt 2, Suppl):720–721.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Cormano J, Mackay G, Holschneider C. Gestational trophoblastic disease diagnosis delayed by the hook effect. Obstet Gynecol 2015;126:811–814.

  • 32.

    Kohorn EI. Persistent low-level “real” human chorionic gonadotropin: a clinical challenge and a therapeutic dilemma. Gynecol Oncol 2002;85:315–320.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    González Aguilera B, Syrios P, Gadisseur R, . Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease. Gynecol Endocrinol 2016;32:439–441.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Cole LA, Khanlian SA, Giddings A, . Gestational trophoblastic diseases: 4. Presentation with persistent low positive human chorionic gonadotropin test results. Gynecol Oncol 2006;102:165–172.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Patel KK, Qavi AJ, Hock KG, . Establishing reference intervals for hCG in postmenopausal women. Clin Biochem 2017;50:234–237.

  • 36.

    Committee on Practice Bulletins-Gynecology, American College of Obstetricians and Gynecologists. ACOG Practice Bulletin #53. Diagnosis and treatment of gestational trophoblastic disease. Obstet Gynecol 2004;103:1365–1377.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Wolfberg AJ, Feltmate C, Goldstein DP, . Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy. Obstet Gynecol 2004;104:551–554.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Wolfberg AJ, Growdon WB, Feltmate CM, . Low risk of relapse after achieving undetectable HCG levels in women with partial molar pregnancy. Obstet Gynecol 2006;108:393–396.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Braga A, Maestá I, Matos M, . Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation. Gynecol Oncol 2015;139:283–287.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Coyle C, Short D, Jackson L, . What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients. Gynecol Oncol 2018;148:254–257.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    FIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. Int J Gynaecol Obstet 2002;77:285–287.

  • 42.

    Agarwal R, Teoh S, Short D, . Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study. Lancet 2012;379:130–135.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Braga A, Torres B, Burlá M, . Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6months after uterine evacuation? Gynecol Oncol 2016;143:558–564.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Edge ST, Greene FL, Byrd DR, , eds. AJCC Staging Manual 8th ed. Chicago, IL: American Joint Committee on Cancer; 2017.

  • 45.

    Abu-Rustum NR, Yashar CM, Bean S, . NCCN Clinical Practice Guidelines in Oncology: Gestational Trophoblastic Neoplasia. Version 2.2019. Accessed August 9, 2018. To view the most recent version, visit NCCN.org.

    • Export Citation
  • 46.

    Ngan HY, Bender H, Benedet JL, . Gestational trophoblastic neoplasia, FIGO 2000 staging and classification. Int J Gynaecol Obstet 2003;83(Suppl 1):175–177.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Gamer EI, Garrett A, Goldstein DP, . Significance of chest computed tomography findings in the evaluation and treatment of persistent gestational trophoblastic neoplasia. J Reprod Med 2004;49:411–414.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Lawrie TA, Alazzam M, Tidy J, . First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2016;6:CD007102.

  • 49.

    Maestá I, Nitecki R, Horowitz NS, . Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: the New England Trophoblastic Disease Center experience. Gynecol Oncol 2018;148:161–167.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Lurain JR, Elfstrand EP. Single-agent methotrexate chemotherapy for the treatment of nonmetastatic gestational trophoblastic tumors. Am J Obstet Gynecol 1995;172:574–579.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    McNeish IA, Strickland S, Holden L, . Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol 2002;20:1838–1844.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Petrilli ES, Twiggs LB, Blessing JA, . Single-dose actinomycin-D treatment for nonmetastatic gestational trophoblastic disease: a prospective phase II trial of the Gynecologic Oncology Group. Cancer 1987;60:2173–2176.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Osborne RJ, Filiaci V, Schink JC, . Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. J Clin Oncol 2011;29:825–831.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Yarandi F, Mousavi A, Abbaslu F, . Five-day intravascular methotrexate versus biweekly actinomycin-D in the treatment of low-risk gestational trophoblastic neoplasia: a clinical randomized trial. Int J Gynecol Cancer 2016;26:971–976.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Matsui H, Iitsuka Y, Seki K, . Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic disease: remission rates and drug toxicities. Gynecol Obstet Invest 1998;46:5–8.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Sung HC, Wu PC, Yang HY. Reevaluation of 5-fluorouracil as a single therapeutic agent for gestational trophoblastic neoplasms. Am J Obstet Gynecol 1984;150:69–75.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Lybol C, Sweep FC, Harvey R, . Relapse rates after two versus three consolidation courses of methotrexate in the treatment of low-risk gestational trophoblastic neoplasia. Gynecol Oncol 2012;125:576–579.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Sita-Lumsden A, Short D, Lindsay I, . Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009. Br J Cancer 2012;107:1810–1814.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59.

    Osborne RJ, Filiaci VL, Schink JC, . Second curettage for low-risk nonmetastatic gestational trophoblastic neoplasia. Obstet Gynecol 2016;128:535–542.

  • 60.

    Garner EI, Feltmate CM, Goldstein DP, . The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol 2005;99:3–5.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61.

    Bolze PA, Mathe M, Hajri T, . First-line hysterectomy for women with low-risk non-metastatic gestational trophoblastic neoplasia no longer wishing to conceive. Gynecol Oncol 2018;150:282–287.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    Clark RM, Nevadunsky NS, Ghosh S, . The evolving role of hysterectomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center. J Reprod Med 2010;55:194–198.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Goldstein DP, Berkowitz RS. Prophylactic chemotherapy of complete molar pregnancy. Semin Oncol 1995;22:157–160.

  • 64.

    Horowitz NS, Goldstein DP, Berkowitz RS. Placental site trophoblastic tumors and epithelioid trophoblastic tumors: biology, natural history, and treatment modalities. Gynecol Oncol 2017;144:208–214.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65.

    Frijstein MM, Lok CAR, Short D, . The results of treatment with high-dose chemotherapy and peripheral blood stem cell support for gestational trophoblastic neoplasia. Eur J Cancer 2019;109:162–171.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66.

    Dantas PRS, Maestá I, Filho JR, . Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors? Gynecol Oncol 2017;147:364–370.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 67.

    Vargas R, Barroilhet LM, Esselen K, . Subsequent pregnancy outcomes after complete and partial molar pregnancy, recurrent molar pregnancy, and gestational trophoblastic neoplasia: an update from the New England Trophoblastic Disease Center. J Reprod Med 2014;59:188–194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68.

    Matsui H, Iitsuka Y, Suzuka K, . Early pregnancy outcomes after chemotherapy for gestational trophoblastic tumor. J Reprod Med 2004;49:531–534.

  • 69.

    Sebire NJ, Fisher RA, Foskett M, . Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following complete or partial hydatidiform molar pregnancy. BJOG 2003;110:22–26.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Williams J, Short D, Dayal L, . Effect of early pregnancy following chemotherapy on disease relapse and fetal outcome in women treated for gestational trophoblastic neoplasia. J Reprod Med 2014;59:248–254.

    • PubMed
    • Search Google Scholar
    • Export Citation
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