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Management of resistant or recurrent gestational trophoblastic neoplasia

Ross S Berkowitz, MD
Donald Peter Goldstein, MD
Neil S Horowitz, MD
Section Editors
Barbara Goff, MD
Don S Dizon, MD, FACP
Deputy Editors
Sadhna R Vora, MD
Sandy J Falk, MD, FACOG


The term gestational trophoblastic neoplasia (GTN) is used when molar and nonmolar pregnancies become malignant. GTN comprises specific histologic entities, including:

Invasive mole


Placental site trophoblastic tumor (PSTT)

Epithelioid trophoblastic tumor (ETT)

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Literature review current through: Dec 2017. | This topic last updated: Dec 19, 2017.
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  1. Brewer JI, Eckman TR, Dolkart RE, et al. Gestational trophoblastic disease. A comparative study of the results of therapy in patients with invasive mole and with choriocarcinoma. Am J Obstet Gynecol 1971; 109:335.
  2. Goldstein DP, Berkowitz RS. Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am 2012; 26:111.
  3. Mutch DG, Soper JT, Babcock CJ, et al. Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer 1990; 66:978.
  4. Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol 2009; 112:654.
  5. Yang J, Xiang Y, Wan X, Yang X. The prognosis of gestational trophoblastic neoplasia patient with residual lung tumor after completing treatment. Gynecol Oncol 2006; 103:479.
  6. Lurain JR. Pharmacotherapy of gestational trophoblastic disease. Expert Opin Pharmacother 2003; 4:2005.
  7. Sita-Lumsden A, Short D, Lindsay I, et al. 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.
  8. McGrath S, Short D, Harvey R, et al. The management and outcome of women with post-hydatidiform mole 'low-risk' gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l(-1). Br J Cancer 2010; 102:810.
  9. Lurain JR, Singh DK, Schink JC. Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7. J Reprod Med 2010; 55:199.
  10. Lurain JR, Nejad B. Secondary chemotherapy for high-risk gestational trophoblastic neoplasia. Gynecol Oncol 2005; 97:618.
  11. Ngan HY, Tam KF, Lam KW, Chan KK. Relapsed gestational trophoblastic neoplasia: A 20-year experience. J Reprod Med 2006; 51:829.
  12. Powles T, Savage PM, Stebbing J, et al. A comparison of patients with relapsed and chemo-refractory gestational trophoblastic neoplasia. Br J Cancer 2007; 96:732.
  13. Newlands ES, Mulholland PJ, Holden L, et al. Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors. J Clin Oncol 2000; 18:854.
  14. Mao Y, Wan X, Lv W, Xie X. Relapsed or refractory gestational trophoblastic neoplasia treated with the etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EP-EMA) regimen. Int J Gynaecol Obstet 2007; 98:44.
  15. Lurain JR, Schink JC. Importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia. J Reprod Med 2012; 57:219.
  16. Bower M, Newlands ES, Holden L, et al. EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. J Clin Oncol 1997; 15:2636.
  17. Osborne R, Covens A, Mirchandani D, Gerulath A. Successful salvage of relapsed high-risk gestational trophoblastic neoplasia patients using a novel paclitaxel-containing doublet. J Reprod Med 2004; 49:655.
  18. Wang J, Short D, Sebire NJ, et al. Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol 2008; 19:1578.
  19. Rustin GJ, Newlands ES, Lutz JM, et al. Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors. J Clin Oncol 1996; 14:2769.
  20. Savage P, Cooke R, O'Nions J, et al. Effects of single-agent and combination chemotherapy for gestational trophoblastic tumors on risks of second malignancy and early menopause. J Clin Oncol 2015; 33:472.
  21. Rathod PS, Kundargi R, Pallavi VR, et al. Refractory Gestational Trophoblastic Neoplasia: A Novel Drug Combination With Paclitaxel and Carboplatin Produces Durable Complete Remission. Int J Gynecol Cancer 2015; 25:1737.
  22. Gordon AN, Kavanagh JJ, Gershenson DM, et al. Cisplatin, vinblastine, and bleomycin combination therapy in resistant gestational trophoblastic disease. Cancer 1986; 58:1407.
  23. DuBeshter B, Berkowitz RS, Goldstein DP, Bernstein M. Vinblastine, cisplatin and bleomycin as salvage therapy for refractory high-risk metastatic gestational trophoblastic disease. J Reprod Med 1989; 34:189.
  24. Azab M, Droz JP, Theodore C, et al. Cisplatin, vinblastine, and bleomycin combination in the treatment of resistant high-risk gestational trophoblastic tumors. Cancer 1989; 64:1829.
  25. Matsui H, Suzuka K, Iitsuka Y, et al. Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors. Cancer 2002; 95:1051.
  26. Wan X, Yang X, Xiang Y, et al. Floxuridine-containing regimens in the treatment of gestational trophoblastic tumor. J Reprod Med 2004; 49:453.
  27. 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.
  28. Zhao J, Lv WG, Feng FZ, et al. Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment. Gynecol Oncol 2016; 142:102.
  29. Termrungruanglert W, Kudelka AP, Piamsomboon S, et al. Remission of refractory gestational trophoblastic disease with high-dose paclitaxel. Anticancer Drugs 1996; 7:503.
  30. Jones WB, Schneider J, Shapiro F, Lewis JL Jr. Treatment of resistant gestational choriocarcinoma with taxol: a report of two cases. Gynecol Oncol 1996; 61:126.
  31. Bianconi M, Jankilevich G, Otero S, et al. Successful salvage of a relapsed high risk gestational trophoblastic neoplasia patient using capecitabine. Gynecol Oncol 2007; 106:268.
  32. Popadiuk C, Power P. Pegylated Liposomal Doxorubicin Is an Active Agent for Chemotherapy-Resistant Choriocarcinoma: A Report of Two Cases. J Reprod Med 2016; 61:215.
  33. Ghorani E, Kaur B, Fisher RA, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet 2017; 390:2343.
  34. Bolze PA, Patrier S, Massardier J, et al. PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes. Int J Gynecol Cancer 2017; 27:554.
  35. Veras E, Kurman RJ, Wang TL, Shih IM. PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases. Int J Gynecol Pathol 2017; 36:146.
  36. Inaguma S, Wang Z, Lasota J, et al. Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1): Analysis in 5536 Cases Revealed Consistent Expression in Trophoblastic Tumors. Am J Surg Pathol 2016; 40:1133.
  37. https://clinicaltrials.gov/ct2/show/NCT03135769 (Accessed on December 19, 2017).
  38. Cagayan MS. High-risk metastatic gestational trophoblastic neoplasia. Primary management with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy. J Reprod Med 2012; 57:231.
  39. Cagayan MS, Magallanes MS. The role of adjuvant surgery in the management of gestational trophoblastic neoplasia. J Reprod Med 2008; 53:513.
  40. Clark RM, Nevadunsky NS, Ghosh S, et al. The evolving role of hysterectomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center. J Reprod Med 2010; 55:194.
  41. Fülöp V, Szigetvári I, Szepesi J, et al. The Role of Surgery in the Management of Gestational Trophoblastic Neoplasia The Hungarian Experience. J Reprod Med 2016; 61:197.
  42. Soper JT. Identification and management of high-risk gestational trophoblastic disease. Semin Oncol 1995; 22:172.
  43. Soper JT. Surgical therapy for gestational trophoblastic disease. J Reprod Med 1994; 39:168.
  44. Soper JT. Role of surgery and radiation therapy in the management of gestational trophoblastic disease. Best Pract Res Clin Obstet Gynaecol 2003; 17:943.
  45. Feng F, Xiang Y, Li L, et al. Clinical parameters predicting therapeutic response to surgical management in patients with chemotherapy-resistant gestational trophoblastic neoplasia. Gynecol Oncol 2009; 113:312.
  46. Lehman E, Gershenson DM, Burke TW, et al. Salvage surgery for chemorefractory gestational trophoblastic disease. J Clin Oncol 1994; 12:2737.
  47. Wong LC, Choo YC, Ma HK. Hepatic metastases in gestational trophoblastic disease. Obstet Gynecol 1986; 67:107.
  48. Grumbine FC, Rosenshein NB, Brereton HD, Kaufman SL. Management of liver metastasis from gestational trophoblastic neoplasia. Am J Obstet Gynecol 1980; 137:959.
  49. Lok CA, Reekers JA, Westermann AM, Van der Velden J. Embolization for hemorrhage of liver metastases from choriocarcinoma. Gynecol Oncol 2005; 98:506.
  50. Crawford RA, Newlands E, Rustin GJ, et al. Gestational trophoblastic disease with liver metastases: the Charing Cross experience. Br J Obstet Gynaecol 1997; 104:105.
  51. Ahamed E, Short D, North B, et al. Survival of women with gestational trophoblastic neoplasia and liver metastases: is it improving? J Reprod Med 2012; 57:262.
  52. Tomoda Y, Arii Y, Kaseki S, et al. Surgical indications for resection in pulmonary metastasis of choriocarcinoma. Cancer 1980; 46:2723.
  53. Fleming EL, Garrett L, Growdon WB, et al. The changing role of thoracotomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center. J Reprod Med 2008; 53:493.
  54. Alifrangis C, Wilkinson MJ, Stefanou DC, et al. Role of thoracotomy and metastatectomy in gestational trophoblastic neoplasia: a single center experience. J Reprod Med 2012; 57:350.
  55. Mapelli P, Mangili G, Picchio M, et al. Role of 18F-FDG PET in the management of gestational trophoblastic neoplasia. Eur J Nucl Med Mol Imaging 2013; 40:505.
  56. Edwards JL, Makey AR, Bagshawe KD. The role of thoracotomy in the management of the pulmonary metastases of gestational choriocarcinoma. Clin Oncol 1975; 1:329.
  57. Sink JD, Hammond CB, Young WG Jr. Pulmonary resection in the management of metastases from gestational choriocarcinoma. J Thorac Cardiovasc Surg 1981; 81:830.
  58. Wang YA, Song HZ, Xia ZF, Sun CF. Drug resistant pulmonary choriocarcinoma metastasis treated by lobectomy: report of 29 cases. Chin Med J (Engl) 1980; 93:758.
  59. Newlands ES, Holden L, Seckl MJ, et al. Management of brain metastases in patients with high-risk gestational trophoblastic tumors. J Reprod Med 2002; 47:465.
  60. Neubauer NL, Latif N, Kalakota K, et al. Brain metastasis in gestational trophoblastic neoplasia: an update. J Reprod Med 2012; 57:288.
  61. Savage P, Kelpanides I, Tuthill M, et al. Brain metastases in gestational trophoblast neoplasia: an update on incidence, management and outcome. Gynecol Oncol 2015; 137:73.
  62. Evans AC Jr, Soper JT, Clarke-Pearson DL, et al. Gestational trophoblastic disease metastatic to the central nervous system. Gynecol Oncol 1995; 59:226.
  63. van Besien K, Verschraegen C, Mehra R, et al. Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue. Gynecol Oncol 1997; 65:366.
  64. Giacalone PL, Benos P, Donnadio D, Laffargue F. High-dose chemotherapy with autologous bone marrow transplantation for refractory metastatic gestational trophoblastic disease. Gynecol Oncol 1995; 58:383.
  65. El-Helw LM, Seckl MJ, Haynes R, et al. High-dose chemotherapy and peripheral blood stem cell support in refractory gestational trophoblastic neoplasia. Br J Cancer 2005; 93:620.