Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.

BACKGROUND: Placental-site trophoblastic tumours are a rare form of gestational trophoblastic disease and consequently information about optimum management or prognostic factors is restricted. We aimed to assess the long-term outcome of stage-adapted management by surgery, chemotherapy, or both for patients with the disorder. METHODS: 35 550 women were registered with gestational trophoblastic disease in the UK (1976-2006), of whom 62 were diagnosed with placental-site trophoblastic tumours and included, retrospectively, in the study. Patients were treated by surgery, chemotherapy, or both. We estimated the probabilities of overall survival and survival without recurrence of disease 5 and 10 years after the date of first treatment, and calculated the association of these endpoints with prognostic factors, including time since antecedent pregnancy, serum concentration of beta-human chorionic gonadotropin, and stage of disease, with both univariate and multivariate analyses. FINDINGS: Probabilities of overall and recurrence-free survival 10 years after first treatment were 70% (95% CI 54-82) and 73% (54-85), respectively. Patients with stage I disease had a 10-year probability of overall survival of 90% (77-100) and did not benefit from postoperative chemotherapy. By contrast, patients with stage II, III, and IV disease required combined treatment with surgery and chemotherapy; probability of overall survival at 10 years was 52% (3-100) for patients with stage II disease and 49% (26-72) for stage III or IV disease. Outcome for patients who had recurrent or refractory disease was poor: only four (22%) patients achieved long-term survival beyond 60 months. Multivariate analysis showed that the only significant independent predictor of overall and recurrence-free survival was time since antecedent pregnancy. A cutoff point of 48 months since antecedent pregnancy could differentiate between patients' probability of survival (<48 months) or death (>/=48 months) with 93% specificity and 100% sensitivity, and with a positive predictive value of 100% and a negative predictive value of 98%. INTERPRETATION: Stage-adapted management with surgery for stage I disease, and combined surgery and chemotherapy for stage II, III, and IV disease could improve the effectiveness of treatment for placental-site trophoblastic tumours. Use of 48 months since antecedent pregnancy as a prognostic indicator of survival could help select patients for risk-adapted treatment. FUNDING: National Commissioning Group.

Value of whole body 18FDG-PET to identify the active site of gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the usefulness of positron emission tomography with 18-fluorodeoxyglucose (18FDG-PET) in locating residual or relapsed gestational trophoblastic neoplasia (GTN). STUDY DESIGN: The Charing Cross GTN database was screened, and 11 patients who had undergone 18FDG-PET were identified. A retrospective analysis was conducted to determine the value of this investigation as compared with other imaging modalities in clinical care. RESULTS: All patients had elevated beta-human chorionic gonadotropin (beta-hCG) at the time of the investigation; none were false positive. In 7 patients the 18FDG-PET scans correctly confirmed the presence (4 of 7 cases) or absence (3 of 7 cases) of disease sites defined by other imaging investigations. In 2 patients positive PET-guided appropriate surgical resection of lung lesions that appeared of equivocal significance on computed tomography (CT) resulted in -hCG normalization. One patient had a pulmonary metastasis on CT not considered positive on 18FDG-PET (false negative). One patient with enlarged mediastinal lymph nodes on CT that were 18FDG-PET positive also had a vascular uterus on magnetic resonance imaging/Dopper ultrasound that was negative on PET (false negative). Hysterectomy led to hCG normalization and cure. The mediastinal lymph nodes were positive on CT and PET due to sarcoidosis (false positive). Patients with serum hCG levels <10 IU/L could have positive PET scans; that can contribute to patient care. CONCLUSION: 18FDG-PET can aid in identifying residual disease sites in women relapsing from previously treated GTN. However, careful evaluation in combination with other imaging modalities is required to reduce the risk of false positive and negative results.

Metabolic activation of temozolomide measured in vivo using positron emission tomography.

The purpose of this research was to quantitate and confirm the mechanism of in vivo metabolic activation of temozolomide. The secondary aims were to evaluate the tumor, normal tissue, and plasma pharmacokinetics of temozolomide in vivo, and to determine whether such pharmacokinetics resulted in tumor targeting. [(11)C]temozolomide kinetics were studied in men using positron emission tomography (PET). It has been postulated that temozolomide undergoes decarboxylation and ring opening in the 3-4 position to produce the highly reactive methyldiazonium ion that alkylates DNA. To investigate this, a dual radiolabeling strategy, with [(11)C]temozolomide separately radiolabelled in the 3-N-methyl and 4-carbonyl positions, was used. We hypothesized that (11)C in the C-4 position of [4-(11)C-carbonyl]temozolomide would be converted to [(11)C]CO(2) if the postulated mechanism of metabolic conversion was true resulting in lower [(11)C]temozolomide tumor exposure. Paired studies were performed with both forms of [(11)C]temozolomide in 6 patients with gliomas. Another PET scan with (11)C-radiolabelled bicarbonate was performed and used to account for the metabolites of temozolomide using a data-led analytical approach. Plasma was analyzed for [(11)C]temozolomide and [(11)C]metabolites throughout the scan duration. Exhaled air was also sampled throughout the scan for [(11)C]CO(2). The percentage ring opening of temozolomide over 90 min was also calculated to evaluate whether there was a differential in metabolic breakdown among plasma, normal tissue, and tumor. There was rapid systemic clearance of both radiolabelled forms of [(11)C]temozolomide over 90 min (0.2 liter/min/m(2)), with [(11)C]CO(2) being the primary elimination product. Plasma [(11)C]CO(2) was present in all of the studies with [4-(11)C-carbonyl]temozolomide and in half the studies with [3-N-(11)C-methyl]temozolomide. The mean contributions to total plasma activity by [(11)C]CO(2) at 10 and 90 min were 12% and 28% with [4-(11)C-carbonyl]temozolomide, and 1% and 4% with [3-N-(11)C-methyl]temozolomide, respectively. There was a 5-fold increase in exhaled [(11)C]CO(2) sampled with [4-(11)C-carbonyl]temozolomide compared with [3-N-(11)C-methyl]temozolomide (P < 0.05). A decrease in tissue exposure [area under the curve between 0 and 90 min (AUC(0-90 min))] to [(11)C]temozolomide was also observed with [4-(11)C-carbonyl] temozolomide compared with [3-N-(11)C-methyl]temozolomide. Of potential therapeutic advantage was the higher [(11)C]radiotracer and [(11)C]temozolomide exposure (AUC(0-90 min)) in tumors compared with normal tissue. [(11)C]temozolomide ring opening over 90 min was less in plasma (20.9%; P < 0.05) compared with tumor (26.8%), gray matter (29.7%), and white matter (30.1%), with no differences (P > 0.05) between tumor and normal tissues. The significantly higher amounts of [(11)C]CO(2) sampled in plasma and exhaled air, in addition to the lower normal tissue and tumor [(11)C]temozolomide AUC(0-90 min) observed with [4-(11)C-carbonyl]temozolomide, confirmed the postulated mechanism of metabolic activation of temozolomide. A higher tumor [(11)C]temozolomide AUC(0-90 min) in tumors compared with normal tissue and the tissue-directed metabolic activation of temozolomide may confer potential therapeutic advantage in the activity of this agent. This is the first report of a clinical PET study used to quantify and confirm the in vivo mechanism of metabolic activation of a drug.

Defining and measuring reproductive concerns of female cancer survivors.

Although women diagnosed with cancer during their childbearing years are at significant risk for infertility, we know little about the relationship between infertility and long-term quality of life (QOL). To examine these relationships, we assessed psychosocial and reproductive concerns and QOL in 231 female cancer survivors. Greater reproductive concerns were significantly associated with lower QOL on numerous dimensions (P<.001). In a multiple regression model, social support, gynecologic problems, and reproductive concerns accounted for 63% of the variance in QOL scores. Women who reported wanting to conceive after cancer, but were not able to, reported significantly more reproductive concerns than those who were able to reproduce after cancer (P<.001). These preliminary data suggest that at least for vulnerable subgroups, the issue of reproductive concerns is worthy of additional investigation to assist cancer survivors living with the threat or reality of infertility.

Routine terminations of pregnancy--should we screen for gestational trophoblastic neoplasia?

After termination of pregnancy for non-medical reasons, the products of conception are often not routinely examined for gestational trophoblastic neoplasia. Between 1995 and 2001 we identified 15 women without and 36 women with a pathological diagnosis of gestational trophoblastic neoplasia at the time of their pregnancy termination. Women without a diagnosis were significantly more likely to have subsequent life-threatening complications of gestational trophoblastic neoplasia (four of 15 vs none of 36; p=0.003), and to require surgical intervention (15 of 15 vs one of 36; p<0.0001) and chemotherapy (nine of 15 vs two of 36; p<0.0001). All women should be screened for gestational trophoblastic neoplasia after termination of pregnancy.

Emerging targeted treatments for malignant glioma.

This paper focuses on the medical management of malignant gliomas, which is currently undergoing change. It suggests that as surgery and radiotherapy are of limited benefit in the treatment of these tumours, medical therapies may have the potential to offer a better alternative. The current therapies for glioma and the targeted agents in clinical trials are reviewed. There is a general acceptance that temozolomide in combination with radiotherapy is replacing radiotherapy alone as first-line therapy in high-grade astrocytic gliomas. Within the realms of clinical research, it can be seen that there is a shift away from therapies targeting the end effect of deregulated cell-cycle control, to targeting specific and individual genetic aberrations in tumours. Finally, the paper questions current clinical trial methodology and tentatively suggests ways in which this may be improved.

Doppler ultrasonography of the uterine artery and the response to chemotherapy in patients with gestational trophoblastic tumors.

PURPOSE: Increasing new blood vessel formation (neoangiogenesis) within tumors is an adverse prognostic factor for survival in several cancers. Neoangiogenesis is usually determined histopathologically and not in vivo. To assess neoangiogenesis in vivo, we have used Doppler ultrasonography (US) to measure the uterine artery pulsatility index (UAPI) in patients with gestational trophoblastic tumors (GTTs). Here, we assess whether the UAPI can provide independent prognostic information predictive of methotrexate resistance (MTX-R), a drug central to the management of GTT. EXPERIMENTAL DESIGN: All patients treated for GTTs between March 1994 and January 1999 had their records reviewed to determine their pretreatment Charing Cross Hospital (CXH) prognostic score, uterine volume, the lowest UAPI of either uterine artery, number of metastases, and human chorionic gonadotropin (hCG) concentration. Of the 164 patients for whom all data were available, 47 subsequently developed MTX-R, defined as a plateaued or rising hCG in two consecutive samples. RESULTS: UAPI, hCG, uterine volume, presence of metastases, and the overall CXH prognostic score were all predictive of MTX-R on univariate analysis. Moreover, the UAPI remained a significant independent predictor of MTX-R on multiple logistic regression analysis. After adjustment for the CXH prognostic score, the odds ratio for the risk of MTX-R in patients with a UAPI < or =1 compared with those with a UAPI >1 was 2.68 (95% confidence interval, 1.25-5.74; P = 0.01). The unadjusted odds ratio for the above comparison was 2.32 (95% confidence interval, 1.14-4.7; P = 0.02). CONCLUSIONS: The UAPI, as an indirect in vivo measure of functional tumor vascularity, independently predicts the response to chemotherapy in GTTs.

Chemotherapy for trophoblastic disease: current standards.

Gestational trophoblastic diseases comprise a rare spectrum of disorders in which the normal regulatory mechanisms controlling the behavior of trophoblastic tissue are lost. They vary from the benign complete and partial hydatidiform moles to the frankly malignant choriocarcinoma and placental site trophoblastic tumors. The majority will be cured by suction curettage, followed by human chorionic gonadotrphin screening but some will go on to need chemotherapy. The majority of patients will be cured even despite the presence of metastatic disease. Patients should have their treatment stratified according to various prognostic factors in order to ensure firstly their disease is eliminated and secondly to reduce the incidence of long-term treatment complications.

Gestational trophoblastic neoplasia: the management of relapsing patients and other recent advances.

The treatment of gestational trophoblastic neoplasia (GTN) represents one of the modern success stories in cancer medicine. Early diagnosis, effective treatments, monitoring of response with a series of serum human chorionic gonadotropin levels, and centralized care have all contributed to this success. Nevertheless, some patients relapse after initial chemotherapy. This review discusses the routine management of GTN and how to treat relapsed disease.

Familial recurrent hydatidiform mole: a review.

This article reviews published data on familial recurrent hydatidiform mole with particular reference to the genetic basis of this condition, the likely outcome of subsequent pregnancies in affected women and the risk of persistent trophoblastic disease following molar pregnancies in these families. Familial recurrent hydatidiform mole is characterized by recurrent complete hydatidiform moles of biparental, rather than the more usual androgenetic, origin. Although the specific gene defect in these families has not been identified, genetic mapping has shown that in most families the gene responsible is located in a 1.1 Mb region on chromosome 19q13.4. Mutations in this gene result in dysregulation of imprinting in the female germ line with abnormal development of both embryonic and extraembryonic tissue. Subsequent pregnancies in women diagnosed with this condition are likely to be complete hydatidiform moles. In 152 pregnancies in affected women, 113 (74%) were complete hydatidiform moles, 26 (17%) were miscarriages, 6 (4%) were partial hydatidiform moles, and 7 (5%) were normal pregnancies. Molar pregnancies in women with familial recurrent hydatidiform mole have a risk of progressing to persistent trophoblastic disease similar to that of androgenetic complete hydatidiform mole.

Management of brain metastases in patients with high-risk gestational trophoblastic tumors.

OBJECTIVE: To analyze the results of current treatment of patients with brain metastases from high-risk gestational trophoblastic tumors. STUDY DESIGN: Consecutive patients treated between June 1981 and the end of 2000 with brain metastases from high-risk gestational trophoblastic tumors were selected from our computerized database. RESULTS: There were 39 patients with cerebral metastases from high-risk gestational trophoblastic tumors, and 30 (79.5%) of these patients are alive and in remission. Four patients died within 8 days of admission from disease extent. If these four patients are excluded, the survival of the remaining 35 patients is 86%. Eight patients had received prior chemotherapy, and 3 died of the disease. The antecedent pregnancy (AP) was term delivery in 23 (59%), and in 2 of those patients there was a prior history of a molar pregnancy in an AP. Six patients had a history of molar pregnancy as the AP, and in 10 the type of AP was uncertain. The presence of both liver and brain metastases was a particularly adverse prognostic combination, and only one of five patients is still alive in remission. No deaths or relapses occurred beyond 30+ months from the initiation of high-dose etoposide, methotrexate and actinomycin D with cyclophosphamide and vincristine chemotherapy. CONCLUSION: With appropriate management, the outlook for patients with brain metastases from high-risk gestational trophoblastic tumors is good, and the majority of patients achieved sustained remission and probably a cure with chemotherapy as the dominant form of treatment. When the tumor is sufficiently chemosensitive, the blood-brain barrier does not prevent disease elimination.

Increased gestational age at evacuation of a complete hydatidiform mole: does it correlate with increased risk of requiring chemotherapy?

OBJECTIVE: To assess whether a complete hydatidiform mole (CHM) carries an increased risk of later requiring chemotherapy in pregnancies continued to term. STUDY DESIGN: The Charing Cross gestational trophoblastic neoplasia (GTN) database was screened between 1973 and 2002 to identify registered singleton CHMs with a known gestational age at the time of evacuation. Of the 8,313 cases 2,800 were centrally histopathologically reviewed by us and confirmed as CHM. The proportion of patients requiring chemotherapyfor both total registered and centrally reviewed patients was analyzed by trimester of evacuation (< 13, 13-24, > 24 weeks). Statistical significance was assessed by the chi2 test. RESULTS: For the total population, including non-centrally reviewed patients, evacuation occurring in the first, second or third trimester was associated with a treatment rate of 13.9% (601 of 4,333), 10.8% (412 of 3,803) and 5.1% (9 of 177), respectively. In patientsfor whom a central pathologic review had been performed to confirm the diagnosis, the treatment rates were 27.7% (525 of 1,897), 27% (241 of 893) and 20% (2 of 10). The higher apparent treatment rates reflect an error in the denominator as we do not review all nontreated cases. In the total population, evacuation in the third trimester correlated with a reduction in risk of subsequent treatment (P<.001). Most of these late deliveries were induced (before adequate ultrasound), whereas the earlier pregnancies were mostly terminated via suction dilatation and curettage. CONCLUSION: There is no evidence that delayed evacuation/delivery of singleton CHM increases the risk of subsequently requiring chemotherapy.

Predictors of quality of life among long-term survivors of gestational trophoblastic disease.

OBJECTIVE: To identify predictors of quality of life (QOL) among women diagnosed with gestational trophoblastic tumor (GTT) 5-10 years earlier. STUDY DESIGN: Utilizing a cross-sectional, descriptive design, 111 survivors completed a comprehensive QOL interview. RESULTS: Univariate analyses revealed that numerous psychosocial variables correlated highly with overall QOL. However, multivariate analysis indicated that the significant predictors of long-term QOL were cancer-specific distress, social support, spiritual well-being, reproductive concerns, gynecologic pain and sexual functioning. These 6 variables accounted for 77% of the variance in the overall QOL score. Post hoc analyses demonstrated that each of the predictors had unique effects on the QOL score. CONCLUSION: The variables identified in this model can guide future research and clinical care to reduce short- and long-term burdens associated with GTT.

Twenty-five years' clinical experience with placental site trophoblastic tumors.

OBJECTIVE: To describe 34 cases of placental site trophoblastic tumor (PSTT) treated at Charing Cross Hospital over 25 years. STUDY DESIGN: Between 1975 and 2001, 1,685 patients with gestational trophoblastic disease (GTD) were treated; 34 of them had PSTT (2%). The computer database clinical notes and the pathology reports were accessed to obtain data on this patient group. The data were subsequently analyzed using Excel computer software. RESULTS: The mean age of the group was 33 years (95% CI 25-41). The antecedent pregnancy was a full-term, normal one in 18 cases (53%), a molar pregnancy in 7 (21%) and a missed abortion in 5 (15%). The mean interval from the last pregnancy to diagnosis was 3.4 years (95% CI 1.9-4.9). The range of serum hCG concentrations at diagnosis was 0-58,000, 79% with levels < 1,000 and 58% < 500. hCG was raised in all with active disease. The most frequent presenting complaint was vaginal bleeding, in 27 cases (79%). At diagnosis, the disease was localized to the uterus in 15 (44%); there was pelvic involvement in 8 (24%) and lung secondaries in 10 (29%). All seven deaths were disease related (21%); all had lung secondaries and presented more than four years since the last pregnancy. Excluding the seven deaths, the primary treatment was surgery alone in 10 cases (37%) (8 hysterectomies and 2 dilatation and curettages); 4 had surgery followed by adjuvant chemotherapy; 5 had neoadjuvant chemotherapy followed by surgery; 1 had chemotherapy alone, and the disease recurred and was successfully rechallenged; and 5 had surgery between chemotherapy cycles. The most common regimens consisted of EMA/CO and EP/EMA. CONCLUSION: Risk factors for death include lung metastatic involvement (50%) and an antecedent pregnancy interval of four years or more (100%). In contrast, those with no extrapelvic disease or a pregnancy interval of less than four years had 100% survival. In two-thirds of patients with disease limited to the uterus, surgery alone was curative. The WHO scoring system for GTD did not correlate with this outcome. Patients with PSTT should be managed separately from those with other types of GTD, as the disease behavior is different.

Quality of life after gestational trophoblastic disease.

OBJECTIVE: To describe the quality of life (QoL) and long-term psychosocial sequelae in women diagnosed with gestational trophoblastic tumor (GTT) 5-10 years earlier. STUDY DESIGN: Utilizing a cross-sectional descriptive design, 111 survivors completed a comprehensive QoL interview. RESULTS: Participants were predominantly married and non-Hispanic white, with a mean age at diagnosis of 30 years and a current mean age of 37 years. This disease-free sample enjoys a good QoL, with physical, social and emotional functioning comparable to or better than comparative norms. However, certain psychological survivorship sequelae persist. Additionally, a sizable number of survivors currently experience significant reproductive concerns. Participants reporting good QoL were less likely to report ongoing coping efforts related to having had this illness, more likely to report greater social support (P < .0001), greater sexual pleasure (P = .0063), and less GTT-specific distress (P < .0001). Fifty-one percent of respondents expressed that they would likely participate in a counseling program today to discuss psychosocial issues raised by having had GTT, and 74% stated that they would have attended a support group program during the initial treatment if it had been offered. CONCLUSION: This information provides insight into the complex survivorship relationships between QoL and sequelae of GTT.

Management and outcome of healthy women with a persistently elevated beta-hCG.

PURPOSE: Raised serum beta human chorionic gonadotrophin (beta-hCG) not due to pregnancy can occur as a consequence of (1) gestational trophoblastic neoplasia (GTN), (2) non-gestational trophoblastic tumours, (3) a false-positive beta-hCG, (4) the menopause or (5) a high normal level. Accurate differentiation between these causes is vital to avoid potentially inappropriate investigations and therapies, which may induce infertility or other serious adverse events. Here we report the United Kingdom experience of patients with an elevated beta-hCG of initial uncertain cause and provide a clinical algorithm for the management of such cases. METHOD: The Charing Cross and Weston Park Hospital GTN databases were screened to identify patients referred with an elevated beta-hCG who were not pregnant and had no previous diagnosis of GTN. RESULTS: Between 1981 and 2004 fourteen women presented with persistently raised serum beta-hCG resulting in diagnostic problems. False-positive beta-hCG was excluded in all. Three patients developed gestational choriocarcinoma after 9-29 months. However, in 11 women no cause for the persistently elevated beta-hCG was found. One of these achieved chemotherapy-induced normalisation of serum beta-hCG, but the remaining 10 underwent surgery and/or chemotherapy without benefit. Thus, 71% (10/14) of patients remain well with unexplained elevated beta-hCG levels. CONCLUSION: Elevated serum and urinary beta-hCG levels in healthy women should be investigated systematically to exclude an underlying malignant process and to avoid inappropriate surgical and medical intervention. Long-term follow-up is required as tumours may not become apparent for many months or years.

Evaluation of deletions in 7q11.2 and 8p12-p21 as prognostic indicators of tumour development following molar pregnancy.

OBJECTIVES: Previous studies have identified loss of chromosomal regions 7p12-q11.2 and 8p12-p21 in choriocarcinoma suggesting that suppressor genes involved in tumour development may be located within these regions. Our objectives were to refine the regions of loss and evaluate these deletions as prognostic indicators of trophoblastic tumour development following molar pregnancy. METHODS: Fluorescent microsatellite genotyping was used to perform deletion mapping in a series of thirty-nine gestational trophoblastic tumours (GTT) including both choriocarcinoma and placental site trophoblastic tumours. RESULTS: Significant loss of heterozygosity (LOH) was found for both regions in GTT that originated in non-molar pregnancies. Although no common interval of loss was found in those GTT with LOH for the 7q11.2 region, for the 8p12-p21 locus, markers D8S1731 and NEFL defined a minimal region of loss in all tumours showing LOH. However, complete LOH of either region occurred in only a minority of tumours (20%; chromosome 7: 24%; chromosome 8) suggesting that loss of neither region is likely to be a primary event in the development of GTT. This was further supported by the observation that no deletions were found in either region for the fourteen GTT that followed complete molar pregnancies. CONCLUSIONS: While we have defined a minimal interval in 8p12-p21 in which tumour suppressor genes involved in GTT are likely to be located, the data suggest that deletions in 7q11.2 or 8p12-p21 are unlikely to be useful prognostic indicators in the management of patients with molar pregnancies.

Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment.

PURPOSE: Malignant ovarian germ cell tumors are rare and knowledge about prognostic parameters currently is limited. This study was undertaken to evaluate long-term outcome of patients with malignant ovarian germ cell tumors (MOGCTs) after chemotherapy and to assess prognostic parameters. PATIENTS AND METHODS: A total of 113 patients with stage IC to IV MOGCTs were included into this retrospective study. Patients were treated at two large regional cancer centers between 1977 and 2003. RESULTS: Ten-year recurrence-free and overall survival rates were 82% and 81%, respectively. A total of 20 patients experienced relapse, all within the first 8 years. Outcome after relapse was poor, with only 10% of patients achieving long-term survival. Univariate and multivariate analyses demonstrated that initial stage of disease (relative risk [RR], 5.96; 95% CI, 3.47 to 10.22; P = .03) and elevation of serum markers beta-human chorionic gonadotropin and alpha-fetoprotein (RR, 3.90; 95% CI, 1.40 to 10.9; P = .009) were significant predictors of overall survival, whereas age at diagnosis was of no prognostic value. CONCLUSION: This is the first study to identify stage and tumor markers as prognostic parameters for patients with MOGCTs. This might help to select patients for risk-adapted treatment. There is need for improvement of therapeutic strategies after relapse.

Chemotherapy for trophoblastic disease: current standards.

Gestational trophoblastic diseases comprise a rare spectrum of disorders in which the normal regulatory mechanisms controlling the behaviour of trophoblastic tissue are lost. They vary from the benign complete and partial hydatidiform moles to the frankly malignant choriocarcinoma and placental site trophoblastic tumours. The majority will be cured by suction curettage, followed by human chorionic gonadotrophin screening, but some will go on to need chemotherapy. The majority of patients will be cured even despite the presence of metastatic disease. Patients should have their treatment stratified according to various prognostic factors in order to ensure firstly their disease is eliminated and secondly to reduce the incidence of long-term treatment complications.