Vaginal metastases in gestational trophoblastic neoplasia

OBJECTIVE: To evaluate the clinical experience and outcomes of patients with gestational trophoblastic neoplasia (GTN) complicated by vaginal metastases. STUDY DESIGN: A review of patients with vaginal metastases from GTN treated at a regional trophoblastic disease center from 1962 to 2006. RESULTS: Vaginal metastases were present in 36 (4.5%) of the 804 patients treated for GTN. FIGO stage was II in 13 patients (36%), III in 22 patients (61%) and IV in 1 patient (3%). Twenty-three patients (65%) were low-risk by modified WHO criteria. The vaginal metastases were most frequently single lesions (61%) on the anterior vaginal wall (49%) with a histologic classification of choriocarcinoma (67%). Significant bleeding necessitated blood transfusion (median, 7 units; range, 1-26 units) in 13 patients (36%). Seven patients (19%) required 1 or more procedures for control of bleeding, including excision, suturing and/or hypogastric artery ligation/embolization. Twenty-three patients (64%) received single-agent chemotherapy with methotrexate and/or actinomycin-D, while 13 patients (36%) received multiagent chemotherapy regimens. CONCLUSION: Overall, 29 (81%) of 36 patients with vaginal metastases were cured. Vaginal metastasis from GTN does not uniformly confer a worse prognosis or necessitate multiagent chemotherapy, although procedures for control of bleeding may be required.     

极高危妊娠滋养细胞肿瘤的治疗策略

妊娠滋养细胞肿瘤(GTN)是一类对化疗极敏感的恶性肿瘤,主要的治疗策略包括全身化疗和对转移瘤的处理。低危患者的总体生存率接近100%,而高危患者的总体生存率为80%～90%。国际妇产科联盟(FIGO)预后评分≥12分或存在肝、脑转移或广泛转移的患者被定义为极高危患者。极高危患者治疗效果差,死亡率高。主要原因有广泛的耐药病灶,肺部病灶进展导致呼吸衰竭以及脑、肝转移灶出血。极高危GTN患者的治疗策略以联合化疗为主,辅以手术、放疗或介入治疗等。当遇到病情严重的极高危患者时,应尽早诊断,稳定患者病情,并建议转诊至有综合诊治能力的妊娠滋养细胞疾病中心。现就极高危GTN患者的治疗策略进行综述。     

Vasoactive intestinal peptide expression in the vaginal anterior wall of patients with pelvic organ prolapse

ObjectivePerimenopausal women are at high risk for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) diseases. In the present study, the expression of VIP in the vaginal epithelium of 70 perimenopausal women was correlated with the severity of POP with or without SUI.Materials and MethodsSeventy biopsy specimens from the anterior vaginal epithelium were obtained from postmenopausal patients. Immunohistochemical labeling for vasoactive intestinal peptide (VIP) and hematoxylin and eosin staining were performed. The VIP innervation was then compared between eight patient groups. Semiquantitative analysis of VIP protein by Western blotting was performed and compared between the eight patient groups.ResultsThe results of the immunohistochemical study showed that the intensity of VIP-immunoreactivity (VIP-ir) in the eight groups was as follows (in decreasing order): Control; POPI; POP II; POP II + SUI; POP III; POP IV and POP III + SUI; and POP IV + SUI. The intensity of VIP-ir was obviously weak and similar among the POP IV, POP III + SUI, and POP IV + SUI groups. This result was validated by the Western blotting analysis. The level of the VIP peptide also deceased in POP patients and was as follows (in decreasing order): Control; POPI; POP II and POP II + SUI; POP III and POP III + SUI; and POP IV and POP IV + SUI.ConclusionThe present study found that reduced VIP innervation in the vaginal epithelium of the perimenopausal women was correlated with the severity of POP with or without SUI.     

Gestational trophoblastic disease: the significance of vaginal metastases

Five patients with gestational trophoblastic disease whose presenting symptom was hemorrhage from vaginal metastases have been added to our previous report. The clinical features, management, and responses to treatment are outlined. All the patients required suturing of the bleeding lesions under general anesthetic to arrest the hemorrhage. In addition one patient needed selective arterial embolization. This did not compromise the response to chemotherapy. We confirm our previous view that the presence of vaginal metastases should be classified as a high-risk factor and that these patients be treated with multiple agent chemotherapy from the outset.     

High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients

PURPOSE: To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supportive care during initial therapy to prevent early mortality. MATERIALS AND METHODS: A series of four consecutive patients with brain metastases from high-risk Stage IV GTN managed at our institution in 2003 and 2005. Patients were assigned FIGO stage and risk score prospectively. Because of concern for chronic toxicity resulting from concurrent moderate dose methotrexate and whole brain radiation, an individualized multidisciplinary approach was used to manage patients. RESULTS: All four women presented with brain and pulmonary metastases; one had multiple liver metastases. Neurological symptoms at presentation included grand mal seizures in 2 patients, left upper extremity hemiparesis and headache each in 1 patient, while 1 patient was asymptomatic. Index pregnancies were term pregnancies in all patients with interval from prior delivery ranging from 2 weeks to 4 years. Two had received prior chemotherapy for postmolar GTN prior to the index pregnancy with incomplete follow-up. Initial hCG values ranged from 26,400 to 137,751 mIU/ml; FIGO risk scores were > or =16 for all patients. Systemic combination chemotherapy was initiated with etoposide and cisplatin followed by moderate/high-dose (500-1000 mg/m(2)) methotrexate combinations. Craniotomy was used before or during the first chemotherapy cycle to extirpate solitary lesions in 3 patients, while stereotactic radiosurgery was administered after the first cycle to treat two brain lesions in the remaining patient. None received whole brain radiation or intrathecal methotrexate. In one patient, selective angiographic embolization was used to control hemorrhage from multiple liver metastases. Two patients required ventilator support early in treatment to allow stabilization from intrathoracic hemorrhage and neutropenic sepsis with respiratory distress syndrome, respectively. Hysterectomy was performed in one patient after completion of salvage chemotherapy. All have completed maintenance chemotherapy and are in prolonged remission (12-24 months). Neurologic sequelae include persistent left upper extremity dyskinesia and weakness in one patient, and episodic grand mal seizures and pseudoseizures in a second patient with a pre-existing seizure disorder. CONCLUSION: This case series documents the utility for a multidisciplinary approach to the treatment of brain metastases from GTN. Using early craniotomy or stereotactic radiosurgery combined with etoposide-cisplatin and moderate/high-dose methotrexate combination chemotherapy, we were able to stabilize patients early in their treatment and avoid whole brain radiation therapy or intrathecal chemotherapy.     

Gestational trophoblastic tumor with liver metastasis after misoprostol abortion

Background  Early elective medical abortion is performed frequently in different countries of the world. Serious complications like gestational trophoblastic neoplasia (GTN) are uncommon and mostly nonmetastatic. High risk metastatic GTN following medical abortion is a rare event which may occur coincidentally. Case  A 26 year-old-woman, gravida 2 para 1, 6 weeks after misoprostol abortion presented with sever nausea, vomiting, and right upper abdominal pain. Human chorionic gonadotropin (hCG) level was 2,500,000 mIU/ml and metastatic work up revealed multiple liver metastases. She totally received nine cycles of EMA-CO (ethoposide- methotrexate- actinomycin- cyclophosphamide, vincristine) regimen for treatment and consolidation. Six months after treatment she is in complete remission. Conclusion  Follow up of patients after medical abortion by means of single serum hCG measurement is highly recommended for early diagnosis of complications including gestational trophoblastic tumor. EMA-CO regimen seems to be an effective and safe treatment for liver metastatic gestational trophoblastic neoplasia.     

Management of Chemoresistant and Quiescent Gestational Trophoblastic Disease

Gestational trophoblastic neoplasia (GTN) is highly chemosensitive and has a high cure rate. Since the introduction of chemotherapy, reliable measurement of human chorionic gonadotropin (hCG) levels, and individualised risk-based therapy into the management of GTN, almost all low-risk and more than 80 % of high-risk GTN cases are curable. However, approximately 25 % of high-risk GTN developed resistance to chemotherapy or relapsed after completion of initial therapy, which often necessitate salvage combination chemotherapy. On the other end of the spectrum, a proportion of patients with gestational trophoblastic disease (GTD) have persistently low levels of hCG, without clinical or radiological evidence of disease, a condition called quiescent GTD. Recently, measurement of hyperglycosylated hCG has been proposed for the management of patients with quiescent GTD. Although representing a small proportion of GTD cases, the management of patients with chemoresistant and quiescent GTD often poses challenges to medical practitioners.     

妊娠滋养细胞肿瘤泌尿系转移患者的治疗及预后

目的评估妊娠滋养细胞肿瘤（GTN）泌尿系转移患者的治疗及预后。方法对1987年1月至2005年12月在北京协和医院就治的19例GTN泌尿系转移患者进行回顾性分析,其中膀胱转移10例,肾转移9例,同时发生膀胱及肾转移的有2例。所有患者均接受以5-氟尿嘧啶（5-FU）为主的联合化疗或EMA-CO化疗,5例患者同时行5-FU膀胱灌注。7例患者行选择性动脉插管栓塞或化疗。5例合并脑转移的患者接受联合化疗同时行甲氨蝶呤（MTX）鞘内注射。结果经过2～22个疗程的化疗后19例患者中11例完全缓解,2例血生化指标缓解带瘤存活,2例住院化疗期间病情恶化放弃治疗,4例合并脑转移死亡。结论GTN膀胱转移患者经过正规的全身加局部化疗预后较好,而肾转移的患者预后相对较差。选择性动脉插管栓塞可以作为急诊处理膀胱转移合并阴道转移大出血患者的首选方法。     

25 years' experience in the treatment of gestational trophoblastic neoplasia in Hungary

OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexate/folinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy.     

Impact of treatment modality on overall survival in women with advanced endometrial cancer: A National Cancer Database analysis

ObjectiveTo evaluate overall survival (OS) in women with advanced endometrial cancer (EC) following chemotherapy alone (CT), neoadjuvant chemotherapy and interval debulking surgery (NACT + IDS) or primary cytoreductive surgery and chemotherapy (PCS + CT).MethodsThe National Cancer Database (NCDB) was queried for patients with stage III/IV EC from 2004 to 2015. Univariable and multivariable Cox proportional hazards analyses assessed the impact of treatment modality upon OS.ResultsOf 48,179 women identified, 5531 received CT (11.5%), 2614 NACT + IDS (5.4%) and 40,034 PCS + CT (83.1%). Median OS was 11.1 months for CT, 25.1 months for NACT + IDS and 60.9 months for PCS + CT (p < 0.001). On multivariate analysis, NACT + IDS (HR 0.44 (0.40, 0.49); p < 0.001) and PCS + CT (HR 0.32 (0.30, 0.35); p < 0.001) were associated with improved OS vs. CT alone. Age, African American race, income, higher Charlson comorbidity index and grade were predictors of worse OS (p < 0.001). On subgroup analysis by stage (III/IV) and histology (Type I/II), PCS + CT improved OS for all patients, compared to NACT + IDS (p < 0.001) and CT (p < 0.001). NACT + IDS was associated with improved OS vs. CT in stage III type I (HR 0.50; 95% CI 0.38, 0.67; p < 0.001), stage IV type I (HR 0.43; 95% CI 0.35, 0.52; p < 0.001), and stage IV type II EC (HR 0.43; 95% CI 0.36, 0.51; p < 0.001), but not stage III type II EC (HR 0.76; 95% CI 0.56, 1.03; p = 0.08).ConclusionsIn women with advanced EC, PCS + CT is associated with improved OS compared to NACT + IDS or CT alone, regardless of stage or histology. Additionally, NACT + IDS is associated with superior OS in stage III type I and all stage IV EC compared to CT alone. Where feasible, surgery should be incorporated into treatment planning in women with advanced EC.     

Vaginal Yolk Sac Tumor: A Case Series and Review of the Literature

ObjectiveTo report diagnosis, treatment, and outcomes of vaginal yolk sac tumor (YST) cases at a single institution and review literature on vaginal YST to outline advancements in diagnosis, treatment, and survival.DesignRetrospective chart review of female patients less than 21 years of age with pathologic diagnosis of vaginal YST treated at a large children's hospital, and summary of a 100-year review of the literature on vaginal yolk sac tumor.SettingChildren's Healthcare of Atlanta, a tertiary center in Atlanta, GA.ParticipantsFemale patients less than 21 years of age diagnosed with vaginal YST.ResultsTwo cases of vaginal YST at our institution are outlined. Both patients presented within the first 2 years of life with vaginal bleeding and were treated successfully with chemotherapy alone. After review of the literature, 137 cases of vaginal YST were found. The mean age at diagnosis was 11 months, and all patients presented with vaginal bleeding. Before 2000, more radical treatments were pursued, and 40% resulted in death. Since the year 2000, treatment has shifted toward chemotherapy and more conservative surgical management, with 51% of vaginal YST cases treated with chemotherapy alone with 92% of patients alive at time of publication.ConclusionOur cases contribute to the limited literature demonstrating the efficacy of conservative management of rare cases of vaginal YST with chemotherapy alone. This case series and review of the literature provide mounting evidence that vaginal YST should be in the differential diagnosis in young girls with vaginal tumors, and conservative management of vaginal YST has excellent outcomes.     

Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy

Objective

To determine factors associated with resistance to methotrexate treatment of low-risk gestational trophoblastic neoplasia (GTN).

Methods

We reviewed the records of 358 patients with low-risk GTN (FIGO stage I and stages II-III, score < 7) treated initially with methotrexate 0.4 mg/kg (max 25 mg) IV push daily × 5 days every 14 days between 1979 and 2009. Actinomycin D 0.5 mg IV push daily × 5 days every 14 days was used in 64 patients who developed resistance or toxicity to initial methotrexate chemotherapy, and combination drug regimens were used in 20 patients who failed single-agent chemotherapy. Adjuvant surgery was used in 34 selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.

Results

The complete response rate to initial methotrexate chemotherapy was 81% (290/358) and the complete response rate to actinomycin D as secondary therapy was 75% (48/64), for an overall complete response rate to sequential single-agent chemotherapy of 94% (338/358). The remaining 20 patients (6%) were all placed into permanent remission with the use of multiagent chemotherapy with or without surgery. Resistance to initial methotrexate chemotherapy was associated with increasing FIGO score (p < .0001), clinicopathologic diagnosis of choriocarcinoma (p = .028), higher pretreatment hCG (p = 0.001) and presence of metastatic, disease (p = .018).

Conclusions

Sequential single-agent chemotherapy with methotrexate (0.4 mg/kg-max 25 mg) followed by actinomycin D (0.5 mg) each given IV push for 5 consecutive days every other week for treatment of low-risk GTN resulted in only 6% of patients requiring multiagent chemotherapy and a 100% survival rate.     

Gestational trophoblastic neoplasia: clinical trends in 8 years at Hospital Universitario de Caracas

OBJECTIVE: To analyze the clinical trends of gestational trophoblastic neoplasia (GTN) at the Department of Obstetrics and Gynecology, Hospital Universitario de Caracas (HUC). STUDY DESIGN: A medical record review was performed of epidemiologic, clinical and diagnostic features of 25 cases of GTN at HUC from 1997 to 2004. RESULTS: During the study period, 35,300 deliveries occurred, and 25 patients were diagnosed with GTN; the prevalence was 0.70:1,000 deliveries. The mean age was 29.2 years. Fifty-six percent were posthydatidiform mole (HM), 36% postchoriocarcinoma (CC), 4% postinvasive mole and 4% postabortion with abundant intermediate trophoblast. Vaginal bleeding was the main symptom in patients with CC. Two cases resembled ectopic pregnancy, and another resembled a vaginal endometrioma. Fifty-two percent of cases were at stage Ib; 76% received single-agent chemotherapy. Hysterectomy was performed in 6 cases. Twenty-one patients achieved remission, 2 showed regression and 2 died. CONCLUSION: GTN had a high prevalence because HUC is a reference center. The most common presentation was post-HM GTN. Vaginal bleeding is frequent in CC and can mimic other gynecologic diseases. Chemotherapy is helpful, and hysterectomy can be performed in selected cases at early stages or with severe vaginal bleed-with a good ing. GTN has a good prognosis, and early diagnosis is possible.     

妊娠性滋养细胞肿瘤阴道转移的临床特点和处理

目的 :研究滋养细胞肿瘤阴道转移患者的临床表现、治疗方法及预后。方法 :回顾分析滋养细胞肿瘤阴道转移 51例的临床资料。阴道转移通过妇科检查和组织活检诊断。结果 :绒癌和侵蚀性葡萄胎阴道转移的发生率分别为 8.6 %和 4 .1% ,转移灶多位于阴道前壁下段。 18例发生破溃大出血。除 2例尚未化疗即死亡外 ,余均采用以 5-FU为主的联合化疗及 (或 )EMA -CO方案化疗。 16例进行了阴道填塞 ,3例因填塞效果差行选择性盆腔动脉栓塞术。接受化疗的患者阴道转移瘤经 1～ 5个疗程的化疗后均完全消失。 51例中 4 4例完全缓解 ,5例部分缓解 ,2例尚未化疗即死亡。完全缓解的 4 4例经定期随访 ,无复发迹象。结论 :多发且较大的阴道转移灶易发生大出血。传统的 5-FU单药及以 5-FU为主的联合化疗仍是治疗滋养细胞肿瘤阴道转移简单有效的方法。选择性动脉栓塞术对难以控制的转移瘤破溃大出血有重要的治疗价值     

妊娠滋养细胞肿瘤Ⅳ期患者的治疗和预后分析

目的 探讨和分析妊娠滋养细胞肿瘤Ⅳ期患者的治疗和预后.方法 1985年1月至2004年1月北京协和医院收治了妊娠滋养细胞肿瘤患者1130例,其中Ⅳ期患者92例,对这些患者的治疗及预后情况进行回顾性分析.结果 92例Ⅳ期患者中,有4例（4%）入院后尚未接受化疗即死亡,其余88例均接受了多药联合化疗,化疗方案采用以氟尿嘧啶为主的联合化疗方案,化疗途径主要是静脉途径以及动脉插管化疗;有32例（35%,32/92）患者在接受化疗的同时还予以手术治疗.92例患者经过治疗后33例获得完全缓解（CR）,37例部分缓解,22例病情进展.CR患者中3例复发.所有患者中共有33例死亡.92例患者中,70例患者有1个或2个脏器的转移,其中27例（39%,27/70）获得CR,20例（29%,20/70）死亡;出现3个脏器转移的17例患者中5例（29%,5/17）获得CR,10例（59%,10/17）死亡;≥4个脏器转移的5例患者中,1例获得CR,3例死亡.转移脏器数量的多少与患者的预后相关（P=0.034）,也与死亡相关（P=0.018）.结论 多药、多途径联合化疗辅助手术治疗是改善Ⅳ期患者预后的主要方法,对于不同脏器转移的治疗应该采用个体化方式.随着转移脏器数量的增加,缓解率明显降低.     

肺叶切除术治疗妊娠滋养细胞肿瘤肺转移的疗效分析

目的 评价肺叶切除术治疗妊娠滋养细胞肿瘤(GTN)肺转移的疗效.方法 对1995年1月-2005年12月间北京协和医院收治的62例凶GTN肺转移行肺叶切除术患者的临床病理资料进行回顾性分析.根据术前临床治疗情况将上述患者分为复发性GTN(A组,10例)、耐药性GTN(B组,28例)和化疗过程中血清人绒毛膜促件腺激素β亚单位(β-hCG)水平呈对数下降、化疗效果满意但肺部病灶持续存在者(C组,25例),其中1例患者分别因耐药与复发两次接受肺叶切除术治疗,放同时进入A组和B组.结果 62例患者总的完伞缓解率为89%(55/62),其中A、B、C组完全缓解率分别为90%(9/10)、79%(22/28)和100%(25/25),B组明显低于C组(P=0.024),其他组间比较,差异则均无统计学意义(P>0.05).3组患者的复发率分别为2/8、15%(3/20)和0.3组高危[即国际妇产科联盟(FIGO)GTN评分≥7分]患者比例分别为90%(9/10)、82%(23/28)和44%(11/25),C组明显低于A、B组(P<0.05);B组患者术前化疗疗程数(7个疗程)明显多于A、C组(分别为3和5个疗程;P<0.05);A、B组患者术前血清β-hCG水平未达正常所占百分比[分别为50%(5/10)61%(17/28)]明显高于C组[为12%(3/25);P<0.05];而3组术后病理阳性率分别为60%(6/10)、36%(10/28)和12%(3/25),C组明显低于A、B组(P<0.05).结论 肺叶切除术对于GTN肺转移是一种有效的治疗方法 .对于肺部病灶相对局限的耐药和复发患者,建议在化疗后适时行肺叶切除术;而对于化疗过程中血清β-hCG水平呈对数下降、化疗效果满意而肺部病灶持续存在的初治患者,町严密随诊,暂不必选择手术治疗.     

妊娠滋养细胞肿瘤患者的死亡原因及相关因素分析

目的探讨妊娠滋养细胞肿瘤患者的死亡原因及相关因素。方法自1985年1月至2004年1月,北京协和医院共收治妊娠滋养细胞肿瘤患者1130例,其中死亡患者64例,本研究对这些患者的死亡原因及相关因素进行回顾性分析。结果64例死亡患者中,初治失败死亡58例,缓解后复发死亡6例;初治失败死亡患者的主要死亡原因为多器官功能衰竭、颅内出血或合并脑疝形成、化疗副反应;缓解后复发死亡患者的死亡原因为复发后病情进展。对初治失败患者的死亡原因进行单因素和多因素分析发现,初治失败患者的死亡与末次妊娠终止至化疗开始的时间（OR=2．857,P〈0．01）、血人绒毛膜促性腺激素β亚单位（β-hCG）水平（P〈0．05）、临床病理类型（OR=3．635,P〈0．05）、临床分期（P〈0．05）以及器官转移数目（OR=2．201,P〈0．01）、耐药（OR=0．181,P〈0．01）有关。结论妊娠滋养细胞肿瘤治疗前应对患者进行正确评估,重视与死亡相关的各种高危因素,以进一步改善患者预后。     

Diagnosis and treatment of high-risk metastatic gestational trophoblastic neoplasia in Hungary

OBJECTIVE: To review results in treatment of high-risk metastatic gestational trophoblastic neoplasia (GTN) in Hungary. STUDY DESIGN: Between January 1, 1977, and December 31, 2006, 142 patients with high-risk metastatic GTN were treated. Patients were 14-51 years of age (average 27.9). We selected primary chemotherapy based on patient GTN stage and prognostic score. RESULTS: Methotrexate, actinomycin-D and cyclophosphamide (MAC) as a primary therapy was used in 100 cases and as second-line chemotherapy in 6 cases. Of the 100 cases, 95 achieved complete remission. Twenty-one high-risk patients were treated with etoposide, high-dose methotrexate with folinic acid rescue, actinomycin-D, cyclophosphamide and vincristine (EMA-CO). Of 17 primary therapies, 13 patients achieved complete remission. Primary cisplatin, etoposide and bleomycin (CEB) was successful in 12 of 14 high-risk cases. Hysterectomy was performed in 42 of 142 high-risk patients; metastases were resected in 26 of 142 of high-risk patients. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO and MAC and EMA-CO. CONCLUSION: Results support that patients with high-risk metastatic GTN should primarily be treated with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens.