Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide
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摘要
Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.
Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.
Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.
引文
1 Biscaro A,Braga A,Berkowitz RS.Diagnosis,classification and treatment of gestational trophoblastic neoplasia.Rev Bras Ginecol Obstet 2015;37:42-51[PMID:25607129 DOI:10.1590/SO100-720320140005198]
2 MaestáI,Braga A.[Challenges of the treatment of patients with gestational trophoblastic disease].Rev Bras Ginecol Obstet 2012;34:143-146[PMID:22584808 DOI:10.1590/S0100-29452012000100020]
3 Seckl MJ,Sebire NJ,Fisher RA,Golfier F,Massuger L,Sessa C;ESMO Guidelines Working Group.Gestational trophoblastic disease:ESMO Clinical Practice Guidelines for diagnosis,treatment and followup.Ann Oncol 2013;24 Suppl 6:vi39-vi50[PMID:23999759 DOI:10.1093/annonc/mdt345]
4 Mangili G,Lorusso D,Brown J,Pfisterer J,Massuger L,Vaughan M,Ngan HY,Golfier F,Sekharan PK,Charry RC,Poveda A,Kim JW,Xiang Y,Berkowtiz R,Seckl MJ.Trophoblastic disease review for diagnosis and management:a joint report from the International Society for the Study of Trophoblastic Disease,European Organisation for the Treatment of Trophoblastic Disease,and the Gynecologic Cancer InterGroup.Int J Gynecol Cancer 2014;24:S109-S116[PMID:25341573 DOI:10.1097/IGC.0000000000000294]
5 Hertz R,Li MC,Spencer DB.Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma.Proc Soc Exp Biol Med 1956;93:361-366[PMID:13379512 DOI:10.3181/00379727-93-22757]
6 Newlands ES,Bagshawe KD,Begent RH,Rustin GJ,Holden L.Results with the EMA/CO(etoposide,methotrexate,actinomycin D,cyclophosphamide,vincristine)regimen in high risk gestational trophoblastic tumours,1979 to 1989.Br J Obstet Gynaecol 1991;98:550-557[PMID:1651757 DOI:10.1111/j.1471-0528.1991.tb10369.x]
7 Berkowitz RS,Goldstein DP.Current advances in the management of gestational trophoblastic disease.Gynecol Oncol 2013;128:3-5[PMID:22846466 DOI:10.1016/j.ygyno.2012.07.116]
8 FIGO Oncology Committee.FIGO staging for gestational trophoblastic neoplasia 2000.FIGO Oncology Committee.Int J Gynaecol Obstet 2002;77:285-287[PMID:12065144 DOI:10.1016/S0020-7292(02)00063-2]
9 Brown J,Naumann RW,Seckl MJ,Schink J.15years of progress in gestational trophoblastic disease:Scoring,standardization,and salvage.Gynecol Oncol 2017;144:200-207[PMID:27743739 DOI:10.1016/j.ygyno.2016.08.330]
10 Braga A,Campos V,Filho JR,Lin LH,Sun SY,de Souza CB,da Silva RCAF,Leal EAS,Silveira E,MaestáI,Madi JM,Uberti EH,Viggiano M,Elias KM,Horowitz N,Berkowitz RS.Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?Gynecol Oncol 2018;148:239-246[PMID:29248195 DOI:10.1016/j.ygyno.2017.12.007]
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2 MaestáI,Braga A.[Challenges of the treatment of patients with gestational trophoblastic disease].Rev Bras Ginecol Obstet 2012;34:143-146[PMID:22584808 DOI:10.1590/S0100-29452012000100020]
3 Seckl MJ,Sebire NJ,Fisher RA,Golfier F,Massuger L,Sessa C;ESMO Guidelines Working Group.Gestational trophoblastic disease:ESMO Clinical Practice Guidelines for diagnosis,treatment and followup.Ann Oncol 2013;24 Suppl 6:vi39-vi50[PMID:23999759 DOI:10.1093/annonc/mdt345]
4 Mangili G,Lorusso D,Brown J,Pfisterer J,Massuger L,Vaughan M,Ngan HY,Golfier F,Sekharan PK,Charry RC,Poveda A,Kim JW,Xiang Y,Berkowtiz R,Seckl MJ.Trophoblastic disease review for diagnosis and management:a joint report from the International Society for the Study of Trophoblastic Disease,European Organisation for the Treatment of Trophoblastic Disease,and the Gynecologic Cancer InterGroup.Int J Gynecol Cancer 2014;24:S109-S116[PMID:25341573 DOI:10.1097/IGC.0000000000000294]
5 Hertz R,Li MC,Spencer DB.Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma.Proc Soc Exp Biol Med 1956;93:361-366[PMID:13379512 DOI:10.3181/00379727-93-22757]
6 Newlands ES,Bagshawe KD,Begent RH,Rustin GJ,Holden L.Results with the EMA/CO(etoposide,methotrexate,actinomycin D,cyclophosphamide,vincristine)regimen in high risk gestational trophoblastic tumours,1979 to 1989.Br J Obstet Gynaecol 1991;98:550-557[PMID:1651757 DOI:10.1111/j.1471-0528.1991.tb10369.x]
7 Berkowitz RS,Goldstein DP.Current advances in the management of gestational trophoblastic disease.Gynecol Oncol 2013;128:3-5[PMID:22846466 DOI:10.1016/j.ygyno.2012.07.116]
8 FIGO Oncology Committee.FIGO staging for gestational trophoblastic neoplasia 2000.FIGO Oncology Committee.Int J Gynaecol Obstet 2002;77:285-287[PMID:12065144 DOI:10.1016/S0020-7292(02)00063-2]
9 Brown J,Naumann RW,Seckl MJ,Schink J.15years of progress in gestational trophoblastic disease:Scoring,standardization,and salvage.Gynecol Oncol 2017;144:200-207[PMID:27743739 DOI:10.1016/j.ygyno.2016.08.330]
10 Braga A,Campos V,Filho JR,Lin LH,Sun SY,de Souza CB,da Silva RCAF,Leal EAS,Silveira E,MaestáI,Madi JM,Uberti EH,Viggiano M,Elias KM,Horowitz N,Berkowitz RS.Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?Gynecol Oncol 2018;148:239-246[PMID:29248195 DOI:10.1016/j.ygyno.2017.12.007]
11 Ngan HY,Kohorn EI,Cole LA,Kurman RJ,Kim SJ,Lurain JR,Seckl MJ,Sasaki S,Soper JT.Trophoblastic disease.Int J Gynaecol Obstet 2012;119 Suppl 2:S130-S136[PMID:22999504 DOI:10.1016/S0020-7292(12)60026-5]
12 Ngan HY,Seckl MJ,Berkowitz RS,Xiang Y,Golfier F,Sekharan PK,Lurain JR.Update on the diagnosis and management of gestational trophoblastic disease.Int J Gynaecol Obstet 2015;131 Suppl 2:S123-S126[PMID:26433668 DOI:10.1016/j.ijgo.2015.06.008]
13 Gillespie AM,Kumar S,Hancock BW.Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy.Br J Cancer 2000;82:1393-1395[PMID:10780516 DOI:10.1054/bjoc.1999.1124]
14 Agarwal R,Teoh S,Short D,Harvey R,Savage PM,Seckl MJ.Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy:a retrospective cohort study.Lancet 2012;379:130-135[PMID:22130490 DOI:10.1016/S0140-6736(11)61265-8]
15 Braga A,Torres B,BurláM,MaestáI,Sun SY,Lin L,Madi JM,Uberti E,Viggiano M,Elias KM,Berkowitz RS.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[PMID:27640962 DOI:10.1016/j.ygyno.2016.09.012]
16 Sarwar N,Newlands ES,Seckl MJ.Gestational trophoblastic neoplasia:the management of relapsing patients and other recent advances.Curr Oncol Rep 2004;6:476-482[PMID:15485618 DOI:10.1007/s11912-004-0079-1]
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