Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53

Gestational trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta. Other terms often used to refer to these conditions include gestational trophoblastic neoplasia and gestational trophoblastic tumor. Histologically distinct disease entities encompassed by this general terminology include complete and partial hydatidiform moles, invasive moles, gestational choriocarcinomas, and placental site trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from gestational trophoblastic disease were substantial. At present, with sensitive quantitative assays for beta-hCG and current approaches to chemotherapy, most women with malignant gestational trophoblastic disease can be cured and their reproductive function preserved. The purpose of this document is to address current evidence regarding the diagnosis, staging, and management of gestational trophoblastic disease.     

Measurement of CA-125 in trophoblastic disease

OBJECTIVES: Physicians treating hydatidiform mole are still seeking means of identifying those patients who will require chemotherapy. The standard accepted method is to follow human chorionic gonadotropin levels but CA-125 measurement has been suggested as a supplement that may be clinically useful. This study was undertaken to validate or refute the one previous study that addresses this issue. CA-125 was measured at the time of hydatidiform mole evacuation to determine (1) whether it would predict the need for chemotherapy and (2) whether it correlated with human chorionic gonadotropin and tumor load in following patients with hydatidiform mole and metastatic gestational trophoblastic disease. PATIENTS AND METHODS: CA-125 was measured in serial weekly samples selected from diagnostic groups of patients with trophoblastic disease. Sixteen patients had hydatidiform mole with spontaneous resolution, fourteen had nonmetastatic gestational trophoblastic tumor, and four had low-risk metastatic disease. Six patients had high-risk metastatic disease. Ten patients had partial hydatidiform mole and one of these required chemotherapy. One patient had primary ovarian choriocarcinoma and three had placental site tumor. RESULTS: The mean preevacuation CA-125 among the 15 patients with complete hydatidiform mole was 40.9 U/ml: 52.5 U/ml for 5 patients who required chemotherapy and 36.2 U/ml for 10 patients who did not require chemotherapy. There was no statistical difference between these values. There was no correlation of CA-125 with hCG. Frequently CA-125 became negative when hCG was still elevated. Among six patients with high-risk disease, CA-125 was elevated in four but in all six patients hCG remained elevated when CA-125 became negative. In nine patients with partial hydatidiform mole CA-125 was elevated prior to mole evacuation and then became negative. The patient with a tetraploid conceptus who required chemotherapy had negative CA-125. With placental site tumor CA-125 was negative, but it was elevated with ovarian choriocarcinoma. CONCLUSION: CA-125 levels do not provide reliable information in the management of patients with gestational trophoblastic disease.     

妊娠滋养细胞肿瘤治疗中的过度与不足

妊娠滋养细胞肿瘤(GTN)包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤,虽然总体治愈率达90%以上,但治疗不当的问题仍然存在。文章从化疗方案的选择、化疗副反应的处理、停止化疗的时机、手术的指征及价值等几方面阐述在临床上存在的对GTN患者治疗的过度与不足。     

Metastatic placental site trophoblastic tumor. Report of a case with complete response to chemotherapy

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia, commonly insensitive to chemotherapeutic agents. CASE: We report on long-term remission in a patient with metastatic PSTT after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine combination chemotherapy. The 27-year-old patient with metastatic lung PSTT was alive, without evidence of disease, > 40 months after treatment. CONCLUSION: Treatment with multiagent chemotherapy can produce long-term remission, even in patients with metastatic PSTT.     

Failure of high-dose chemotherapy with peripheral blood stem cell support for refractory placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. The metastatic and refractory cases have a very poor prognosis. To our knowledge, this is the first report of the application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for the treatment of refractory metastatic PSTT. A 36-year-old woman had a metastatic PSTT refractory to several lines of chemotherapy. She was treated with high dose of carboplatin and etoposide with autologous PBSCT. She showed only a temporary response to high-dose chemotherapy with PBSCT support and died of disease.     

滋养细胞肿瘤患者再妊娠相关问题

妊娠滋养细胞肿瘤（GTN）包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤。由于GTN多发生于育龄妇女,治疗的同时保留患者的生育功能显得尤为重要。文章详细阐述了保留生育功能治疗GTN的方法（包括化疗、栓塞治疗、保守性手术、放疗等）及其对生育功能的影响,并对治疗后再妊娠的结局进行了阐述。     

Role of hysterectomy in management of gestational trophoblastic disease

OBJECTIVE: To evaluate incidence, indications, and outcome of hysterectomy in women presenting with gestational trophoblastic disease. METHODS: A prospective observational study using a standardized protocol for registration, assessment, and treatment of gestational trophoblastic disease. A total of 5976 consecutive new patients registered between January 1986 and December 2000 with a diagnosis of gestational trophoblastic disease. The setting was a supraregional tertiary referral center for gestational trophoblastic disease. RESULTS: Between January 1 1986 and December 31 2000, 5976 new patients with a diagnosis of gestational trophoblastic disease were registered at Weston Park Hospital, Sheffield. Of these patients, 301 required chemotherapy. Forty patients underwent hysterectomy. The average pretreatment risk score in women who had hysterectomy was 7.4. The mean time interval between diagnosis of molar disease and hysterectomy was 17 months. Indications for hysterectomy included uncontrollable vaginal or intraabdominal bleeding, localized chemo-resistant disease, and placental site trophoblastic tumor. In this group, 31 of 40 women had chemotherapy and 14 patients needed more than one regimen. These women were also more likely to have atypical histology (3 invasive moles, 6 placental site trophoblastic tumours, 13 choriocarcinomas, and 2 dimorphic tumours). There were 10 deaths in all registered patients with molar disease and 4 of these were in the hysterectomy group. CONCLUSION: Hysterectomy was performed in 1 in 150 northern UK women with gestational trophoblastic disease. Patients needing hysterectomy represent an increased-risk group as indicated by their high pretreatment risk scores, atypical histology, frequent use of salvage chemotherapy, and higher mortality.     

Placental site trophoblastic tumor: an overview

OBJECTIVE: To analyze 15 consecutive cases of placental site trophoblastic tumor seen in a single reference institution for gestational trophoblastic disease, San Gerardo Hospital, Monza, Italy. STUDY DESIGN: Consecutive patients affected by placental site trophoblastic tumors were selected from our computerized database. RESULTS: There were 15 patients with placental site trophoblastic tumor, with a median age of 35 years. The antecedent pregnancy was a term one in 6 cases (40%), a miscarriage in 4 cases (27%), a termination in 2 cases (13%) and a molar abortion in 2 cases (13%). In 1 case the previous pregnancy was unrecognized. The median interval from the last pregnancy was 12 months, and the presenting symptom in 11 cases was vaginal bleeding, in 2 cases amenorrhea, in 1case a nephrotic syndrome and in 1 case, presenting with metastatic disease, hemoptysis. Six patients were treated using neoadjuvant chemotherapy with etoposide/methotrexate/actinomycin-etoposide/ vincristine (EMA-CO) followed in 5 of 6 (83%) cases by hysterectomy. One patient had only medical treatment with EMA-CO because of a strong desire for or childbearing and had a complete response; after 15 months she was free from disease. The last 9 patients underwent surgery as the first therapy. Among these patients 1 had presented with metastatic pulmonary disease and underwent chemotherapy, with complete disappearance of the pulmonary lesions. Two of these 9 patients had a relapse; the mirst patient had a pelvic and bladder relapse, and 14 months after multiple chemotherapy and surgery, she died. The second had a suburethral relapse 2 months after initial surgery; after chemotherapy and surgery she was well and free of disease. CONCLUSION: Our experience suggests that the role of chemotherapy may be reconsidered not only for metastatic disease but als of or uterine disease when choosing conservative management in young, fertile patients who desire childbearing. Chemotherapy may play an important role in avoiding relapse or early metastases even in patients who underwent hysterectomy as primary treatment.     

Successful management of metastatic placental site trophoblastic tumor with multiple pulmonary resections

INTRODUCTION: Placental site trophoblastic tumor (PSTT) is an uncommon variant of gestational trophoblastic disease. Most of these tumors are confined to the uterus and treated with a simple hysterectomy. However, 30% of these patients will present with metastatic disease. These patients are typically treated with a hysterectomy followed by adjuvant multiagent chemotherapy. Unfortunately, PSTT is relatively resistant to chemotherapy when compared to other forms of gestational trophoblastic disease. Consequently, these patients have a poor prognosis. CASE: We present a case report of a 26-year-old female with multiple metastatic lesions to the lungs unresponsive to chemotherapy who was managed with multiple pulmonary resections. She has remained clinically free of disease at 28 months of follow up. CONCLUSION: A patient with metastatic PSTT was successfully managed with radical surgical resection of chemotherapy-resistant sites.     

中间型滋养细胞肿瘤诊断与鉴别诊断

中间型滋养细胞肿瘤(ITTs)包括胎盘部位滋养细胞肿瘤(PSTT)和上皮样滋养细胞肿瘤(ETT),是比较罕见的妊娠滋养细胞疾病。PSTT主要表现为不规则阴道流血和闭经;ETT主要表现为不规则阴道流血。影像学和血清学等辅助检查在诊断ITTs中起一定作用,病理是确诊的金标准。手术是主要的治疗方式,根据具体病情联合放化疗。早期诊断和合理治疗可明显改善预后。     

Serum levels of macrophage colony-stimulating factor in trophoblastic disease

OBJECTIVES: The aims of this study were to measure levels of colony stimulating factor (CSF-1) in patients with trophoblastic disease, to determine whether such measurement may be useful to supplement measurement of the prognostically reliable human chorionic gonadotrophin (hCG), and to assess whether measurement of CSF-1 may be helpful in predicting requirement for chemotherapy in patients with hydatidiform mole. METHODS: Serial weekly serum samples were selected for CSF-1 assay from representative diagnostic groups of patients with trophoblastic disease: hydatidiform-mole with spontaneous resolution, low-risk post-hydatidiform-mole trophoblastic tumor, partial hydatidiform mole, high-risk metastatic gestational trophoblastic tumor, primary ovarian choriocarcinoma, and placental site trophoblastic tumor. hCG was measured by an in-house radioimmunoassay that measures all parts of the hCG molecule. CSF-1 was measured by radioimmunoassay with (125)I-labeled recombinant CSF-1. The upper level of normal CSF-1 was taken as 8 ng/ml. RESULTS: In this study of 45 patients with trophoblastic disease, some very high levels of CSF-1 were encountered. In a few patients there was dramatic correlation with hCG. Generally, however, CSF-1 and hCG did not correlate. CSF-1 was frequently not elevated when hCG was still significantly elevated and conversely CSF-1 was elevated when hCG was negative. CONCLUSION: The measurement of CSF-1 does not appear to be useful in managing trophoblastic disease as it does not correlate with the level of hCG. Occasionally, high levels of CSF-1 were found in patients with trophoblastic disease.     

Advances in the understanding of placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease. The tumor represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy. It displays a wide spectrum of behavior, and when metastatic, can be difficult to control even with surgery and chemotherapy. Because of PSTT's rarity, limited information is known about its natural history. Several recent studies have indicated that mitotic index is an important prognostic indicator. Advances in chemotherapeutic regimens have also improved clinical response in metastatic disease.     

Placental site trophoblastic tumor presenting with scalp metastases

Placental site trophoblastic tumor (PSTT) usually presents with vaginal bleeding or amenorrhea and an enlarged uterus. Metastasis to the skin as the presenting sign, or as a metastatic site, has not been previously reported with PSTT. We report a case of PSTT in which the presenting sign was scalp metastases and the only other disease was a small focus in the uterus. The patient responded to multi-agent chemotherapy and repeated skin resection at the local site. She received 16 alternating cycles of etoposide-methotrexate-actinomycin D and cytoxan-oncovin (EMA/CO) and is currently without evidence of disease. Clinicians caring for reproductive age women should remain aware that gestational trophoblastic disease (GTD) may present in an unusual manner.     

上皮样滋养细胞肿瘤的诊治

上皮样滋养细胞肿瘤(epithelioid trophoblastic tumor,ETT)起源于绒毛膜型中间型滋养细胞,非常罕见,生育期年龄妇女多见,常继发于足月妊娠,临床表现与胎盘部位滋养细胞肿瘤(placental site trophoblastic tumor,PSTT)相似,约70%出现阴道流血,血h CG水平中度升高。手术是ETT主要的治疗手段,化疗效果目前仍存在争议。无转移者预后良好,但一旦转移预后极差。     

胎盘部位滋养细胞肿瘤的诊治

胎盘部位滋养细胞肿瘤是一种较少见的妊娠滋养细胞肿瘤,其最常见的临床表现为停经和阴道流血,确诊必须以组织病理学诊断为依据,免疫组化检查在其诊断与鉴别诊断中具有重要意义。其对化疗的敏感性不如其他类型滋养细胞肿瘤,手术是首选的治疗方法,对有不良预后因素的患者还应多药联合化疗进行综合治疗。对于年轻、有生育要求、且子宫病灶局限的病例可以考虑采用保留生育功能治疗。     

Resolution of pulmonary metastases with chemotherapy in a patient with placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT), a rare variant of gestational trophoblastic disease, was first described in 1976. PSTT is usually seen in young women, generally treated by hysterectomy, and is associated with a 20% fatality rate. The development of metastases secondary to PSTT is associated with an extremely poor prognosis. Metastatic PSTT has generally been resistant to chemotherapy although one complete and some partial responses have been noted previously. We report a case of a complete chemotherapeutic response in a patient with pulmonary metastases.     

Placental site trophoblastic tumors and epithelioid trophoblastic tumors: Biology,natural history,and treatment modalities

Placental site (PSTT) and epithelioid trophoblastic tumor (ETT) are rare types of gestational trophoblastic neoplasia (GTN) that arise from intermediate trophoblast. Given that this cell of origin is different from other forms of GTN, it is not surprising that the clinical presentation, tumor marker profile, and treatment paradigm for PSTT and ETT are quite different as well. The mainstay for therapy for stage I PSTT and ETT is hysterectomy with adjuvant chemotherapy reserved for those presenting greater than four years from the antecedent pregnancy. Surgery is also important for metastatic disease. There is no standardized chemotherapy regimen for advanced stage disease but often consists of a platinum-containing combination therapy, usually EMA-EP or TE/TP. Despite its rarity, PSTT and ETT account for a disproportionate percentage of mortality from GTN likely resulting from their relative chemotherapy resistance. Novel therapeutic modalities therefore are needed to improve the outcomes of women with advanced stage or resistant PSTT and ETT.     

Prolonged remission of recurrent, metastatic placental site trophoblastic tumor after chemotherapy

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a form of gestational trophoblastic neoplasm that is frequently resistant to chemotherapy. In most cases disease is confined to the uterus and can be cured by curettage or simple hysterectomy. Patients with metastases, however, frequently have progression of disease and die despite aggressive multiagent chemotherapy. CASE: A 31-year-old woman was found on review of uterine curettings to have a PSTT. Imaging studies revealed multiple lung lesions, a liver lesion, and an enlarged irregular uterus. Hysterectomy and staging surgery revealed a large tumor in the endometrial cavity and multiple metastases. She was treated with etoposide-methotrexate-dactinomycin and cyclophosphamide-vincristine and had a complete clinical remission. Six months later, however, she had a recurrence. She was then treated with six cycles of etoposide-methotrexate-dactinomycin and etoposide-cisplatin. Three years after completion of the second regimen she is without evidence of disease. CONCLUSION: Treatment with multiagent chemotherapy can produce long-term remission, even in patients with recurrent, metastatic PSTT. Addition of platinum may be helpful in patients who have recurred or progressed after treatment with non-platinum-containing regimens.     

用CDBFI技术检测恶性妊娠性滋养细胞肿瘤的子宫动脉血流阻力指数

目的：探讨恶性妊娠性滋养细胞肿瘤（ＭＧＴＴ）患者的子宫动脉血液动力学变化。方法：采用彩色多普勒血流显像（ＣＤＢＦＩ）技术测定了正常妇女２０例和ＭＧＴＴ３０例化疗前、后的子宫动脉血流阻力指数（ＲＩ）值。结果：化疗前ＭＧＴＴ组的子宫动脉ＲＩ值较正常组低（Ｐ＜０．０１），显示了ＭＧＴＴ子宫血流低阻特性；化疗有效者，经≥３个疗程化疗后子宫动脉ＲＩ值较化疗前明显增高（Ｐ＜０．０５）。结论：用ＣＤＢＦＩ技术检测子宫动脉血流参数有助于ＭＧＴＴ的诊断及观察化疗疗效。