Metastatic Testicular Germ Cell Tumors Research Articles

Late relapse after treatment for nonseminomatous testicular germ cell tumors according to a single center-based experience.

The introduction of cisplatin-based systemic chemotherapy into the clinical routine has resulted in a substantial improvement of the recurrence-free and long-term survival of patients with metastatic testicular germ cell tumors. Late relapses after the completion of first-line therapy, comprising systemic chemotherapeutic treatment in combination with a complete resection of residual tumor masses visible in about 25-50% of patients, have been reported to occur in 1-5% of patients later than 2 years following the initial treatment. It has been reported that the risk for the development of late recurrence is correlated to the tumor burden at first diagnosis and/or the presence of teratomatous components within the primary testicular cancer. Second-line chemotherapy in combination with surgery, although not very well standardized, has been recommended as the most effective therapeutic regimen during the treatment of patients suffering from late recurrent germ cell tumors. Herein, we report our single-center experience with 14 patients in different clinical stages who developed late relapse after successful first-line therapy. In the present series, the risk for late relapse was not correlated to the clinical stage at first diagnosis or the presence of teratomatous elements within the primary tumor. It became evident that in selected cases chemotherapy alone can be considered a curative treatment option.

Use of fluorodeoxyglucose positron emission tomography scans in patients with advanced germ cell tumour following chemotherapy: single-centre experience with long-term follow up.

Fluorodeoxyglucose positron emission tomography (FDG-PET) may detect residual or recurrent malignancy in patients with germ cell tumours (GCT) following chemotherapy. The objective of the present study was to evaluate the use of FDG-PET in the setting of advanced GCT, and to determine the influence of FDG-PET on subsequent patient management. A computerized search of the patient database of the Department of Medical Oncology, Guy's Hospital, London, United Kingdom, and a manual search of medical records, were conducted. All male patients with metastatic or extragonadal GCT treated with chemotherapy between July 1996 and June 1999 inclusive were identified. Data from patients that had a PET scan following chemotherapy were analysed. Reported PET scan findings were compared with subsequent clinical management and patient outcome. A total of 30 patients with metastatic testicular GCT and three patients with extragonadal GCT were treated with chemotherapy. Of these, 15 patients (12 testicular; three extragonadal; 10 non-seminoma; and five seminoma) were investigated following chemo-therapy with at least one FDG-PET scan. Seven patients had two or more PET scans, and a total of 26 FDG-PET scans was performed. The most frequent indication for PET scan was evaluation of a residual mass (11 patients). Three patients had an FDG-PET to evaluate thymic prominence. Minimum follow up from first PET scan was 18 months. Three of 26 PET scans had false positive findings. Four PET scans yielded findings of equivocal significance with repeat PET scan recommended. Relapse of disease occurred in three patients; two of whom had normal previous PET scans and one had a previous equivocal result. PET had an impact on patient management in only one case where it 'prompted' surgical excision of a residual mass. Normal PET scans provided reassurance in patients with residual small masses but did not alter their subsequent -management. A residual mass was the most common indication for PET. For the majority of patients PET did not have a discernible influence on clinical management. Oncologists should exercise caution in their interpretation of PET scan findings and guidelines for the appropriate use of PET in testicular cancer management need to be developed. Prospective trials are required to define the clinical role of PET in this setting.

849 Multidisciplinary treatment of central nervous system (CNS) metastases in patients with metastatic testicular germ cell tumor (GCT)

849 Multidisciplinary treatment of central nervous system (CNS) metastases in patients with metastatic testicular germ cell tumor (GCT)

Curing metastatic cancer: lessons from testicular germ-cell tumours.

Most metastatic cancers are fatal. More than 80% of patients with metastatic testicular germ-cell tumours (TGCTs), however, can be cured using cisplatin-based combination chemotherapy. Why are TGCTs more sensitive to chemotherapeutics than most other tumour types? Answers to this question could lead to new treatments for metastatic cancers.

Mediastinal metastases from testicular nonseminomatous germ cell tumors: Patterns of dissemination and predictors of long-term survival with surgery

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors. Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.8 years, who required at least one surgical procedure to remove residual mediastinal disease. Pathologic types of resected residual mediastinal disease were necrosis (15%), teratoma (59%), persistent nonseminomatous germ cell cancer (15%), and non-germ cell carcinomatous degeneration (11%). Twelve variables were evaluated by univariate analyses, and four variables potentially statistically significant at P <.10 were subsequently entered into a Cox regression model. Results: All patients demonstrated metastases to the visceral mediastinum. Fewer patients also demonstrated metastases to the paravertebral sulcus or anterior compartments (16% and 7%, respectively). Overall 5- and 10-year survivals were 86% ± 2% and 74% ± 4%, respectively. According to multivariate analysis, disease-related survival was negatively influenced by an elevated preoperative β-human chorionic gonadotropin level (P =.028) and adverse pathologic characteristics of residual mediastinal disease (P =.006). Conclusions: Testicular nonseminomatous germ cell tumors follow a predictable pattern of mediastinal dissemination, primarily following the course of the thoracic duct and its major tributaries. Patients who require surgery to remove residual mediastinal disease after cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors have good to excellent long-term survivals. These results justify an aggressive surgical approach, including multiple surgical procedures if clinically indicated.J Thorac Cardiovasc Surg 2003;125:913-23

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours.

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high β-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.

A new prognostic model for testicular germ cell tumours.

In univariate analyses of patients with metastatic testicular germ cell tumours (TGCT), both the International Germ Cell Consensus Classification (IGCCC) and serum lactate dehydrogenase (S-LD) isoenzyme 1 catalytic concentration (S-LD-1) significantly predicted survival. In complementary analyses of 81 patients with metastatic TGCT, S-LD and S-LD-1 classified the prognosis differently for 23 patients. In multivariate Cox hazard analyses of risk factors, only IGCCC and S-LD-1 predicted the prognosis (p=0.036, and p=0.0007, respectively). A new prognostic model based on prognostic information from main histology, IGCCC, and S-LD-1 changed the prognostic prediction by IGCCC for 19 patients (24%). Judged by to the area under the curve for receiver operation characteristics curves, the new model predicted five-years survival for the patients better than IGCCC and a modified version of the third edition of the TNM classification (p=0.025, and p=0.01, respectively). However, new studies should validate the new model before it is recommended as a general classification system of patients with metastatic TGCT.

Symptomatic Renal Metastasis of a Testicular Seminoma Mimicking Pelvicaliceal Transitional Cell Carcinoma

Metastases to the kidney are common in patients with carcinomatosis, but tend to be small, bilateral and asymptomatic.1, 2 The kidneys are not an uncommon site of metastatic testicular germ cell tumor, but when metastases occur they are more frequently associated with primary nonseminomatous testicular germ cell tumor or mixed testicular tumor. Symptomatic metastasis from classic seminomatous germ cell tumor is uncommon although metastases have been described as part of generalized (stage III) disease.1, 2 We report on a patient with renal metastasis of a classic testicular seminoma presenting with hematuria and a renal pelvicaliceal mass. CASE REPORT

Early nasogastric tube removal combined with metoclopramide after postchemotherapy retroperitoneal lymph node dissection for metastatic testicular nonseminomatous germ cell tumor

Objectives. To evaluate the efficacy of combining early nasogastric tube (NGT) removal and metoclopramide after postchemotherapy retroperitoneal lymph node dissection (RPLND) in decreasing complications, time to diet tolerance, and discharge. Methods. We performed a retrospective study of 31 patients who underwent postchemotherapy RPLND at the University of Texas M. D. Anderson Cancer Center between 1994 and 1996, who were treated with a clinical care pathway that included NGT removal on postoperative day 1 and immediate use of promotility agents such as metoclopramide. A comparison was made with 42 historic controls treated from 1988 to 1994 who were managed with an NGT until the return of flatus and minimal promotility agents. Results. Both groups had comparable age, chemotherapy, and surgical procedures. The study group had fewer complications, with an earlier tolerance of solid food (median 5 ± 2.5 days compared with 7 ± 5.1 days in controls, P = 0.000) and discharge (median 6 ± 2.6 days compared with 9 ± 6.9 days in controls, P = 0.000). NGT replacement was required in 3.2% of study patients versus 9% of controls. Multiple regression analyses demonstrated that the number of NGT days was an independent predictor of early return of bowel function and length of hospitalization ( P = 0.000), and metoclopramide was not. Conclusions. Early NGT removal combined with metoclopramide after postchemotherapy RPLND allowed earlier diet tolerance and shortened hospital stays without increased complications. The role that promotility agents play as a necessary component of safe, early NGT removal is unclear.

EXPRESSION PATTERNS OF CANCER TESTIS ANTIGENS IN TESTICULAR GERM CELL TUMORS AND ADJACENT TESTICULAR TISSUE

The human cancer-testis antigens (CTAs) are a group of tumor specific antigens recognized by cytotoxic T lymphocytes whose expression occurs in human malignancies as well as in normal testicular tissue. We studied a series of CTA gene transcripts in testicular germ cell tumors of various histological types to test the hypothesis that the expression of CTA in testicular germ cell tumors reflects developmental stages of tumorigenesis rather than constitutive tumor antigens recognized by cytotoxic T lymphocytes. Total RNA was obtained from 31 primary and 3 metastatic testicular germ cell tumors, and 11 parenchymal tissues adjacent to the testicular germ cell tumors. We performed an expression study of the CTA genes MAGE-A, MAGE-B, GAGE, PAGE-1, HOM-MEL-40 (SSX2), NY-ESO-1, LAGE-1 and SCP-1 in these samples using reverse transcriptase-polymerase chain reaction. The results showed that expression patterns of CTA genes depended on the histological differentiation of the testicular germ cell tumors. Overall CTA expression was more common in seminomas than in nonseminomatous germ cell tumors. Specifically all 13 seminomas (100%) demonstrated the positive expression of MAGE-B1 and MAGE-B2, while 3 of 17 nonseminomatous germ cell tumor samples (18%) showed positive expression of these genes. All 5 teratomatous elements (100%) had homogenous null expression with regard to all CTA genes examined. In addition, we detected deficiencies in CTA expression in 7 of 11 parenchymal tissues adjacent to the testicular germ cell tumors (64%). These data support the idea that CTA transcripts in testicular germ cell tumors serve as developmental footprints of testicular germ cell tumors rather than as constitutive tumor antigens recognized by cytotoxic T lymphocytes.

Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ cell tumors can be cured in 70-80% of patients. Patients refractory to cisplatin-based chemotherapy have a very poor prognosis. Several mechanisms have been discussed for the development of platinum resistance such as a decreased intracellular concentration of the drug, increased repair of the drug induced damage, or an altered apoptotic response to this damage. Various chemotherapeutic agents have been evaluated in intensively pretreated or cisplatin-refractory patients. Neither the antracyclines nor vinorelbine, bendamustine, topotecan, nor biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%) with individual patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two recent studies have evaluated gemcitabine in refractory germ cell tumors, demonstrating a response rate of 17% (95% CI: 7-28%) in 52 intensively pretreated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem cell transplantation. The nonhematologic toxicity of weekly gemcitabine at doses of 1000-1250 mg/m2 was tolerable and hematologic side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ cell tumors performed by the German Testicular Cancer Study Group (GTCSG) are evaluating oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may make it possible to test the use of alternating treatment strategies in patients with "poor prognostic" disease or as salvage treatment. It is hoped that the increase in knowledge of the molecular mechanism of testicular cancer may lead to the development of new therapeutic options.

Resection of residual masses alone: an alternative in surgical therapy of metastatic testicular germ cell tumors after chemotherapy

Objectives. The standard approach in postchemotherapy surgery of testicular cancer is retroperitoneal lymph node dissection. However, because of its high rate of morbidity (mainly loss of antegrade ejaculation), various approaches have been suggested. We present our experience in limited postchemotherapy surgery for residual masses. Methods. Seventy-five patients underwent resection of residual masses after chemotherapy. After tumor marker levels returned to normal, patients with residual lymph nodes greater than 2 cm in nonseminomatous germ cell tumors and greater than 4 cm in seminomas and any resectable parenchymal lesions were candidates for the limited surgery. We performed 82 operations on 75 patients. The ejaculatory function of the patients after surgery was assessed during their last visit. Results. The histologic features of the resected specimens were necrosis/fibrosis, teratoma, and viable cancer in 33.3%, 45.3%, and 21.3%, respectively. Two patients had a relapse in the retroperitoneum, two in the thorax, and one in the liver. In 3 of these 5 patients, repeated limited resections were performed. At a mean follow-up of 37.4 months (range 3 to 127), 62 patients (82.7%) had no evidence of disease, 8 patients (10.7%) had died, 3 patients were alive with disease, and 2 patients were lost to follow-up. Removal of the residual masses was incomplete in 7 patients (9.3%). Five (45.5%) of 11 patients with viable cancer cells in the specimen had no evidence of disease after complete removal of the residual mass; in the group with incomplete removal, all patients had evidence of disease. The prognosis of patients with incomplete resections and those with viable cancer cells in the specimen was found to be worse than for those with complete resections and those with other histologic findings. Antegrade ejaculation was preserved in 58 (93.6%) of the 62 living patients. Conclusions. In the present series, our surgical technique resulted in an excellent antegrade ejaculation rate and a rate of relapse attributable to the surgical technique that was very low (3%). Thus, removal of the residual mass only may be a beneficial option in postchemotherapy surgery.

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era

The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

Serum lactate dehydrogenase isoenzyme 1 as a prognostic predictor for metastatic testicular germ cell tumours - reply

Serum lactate dehydrogenase isoenzyme 1 as a prognostic predictor for metastatic testicular germ cell tumours – reply

Treatment of patients with cisplatin-refractory testicular germ-cell cancer

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ-cell tumors can be cured in 70% to 80% of patients. The combination of cisplatin, etoposide and bleomycine (PEB) is considered standard therapy. Patients refractory to cisplatin-based chemotherapy have a markedly poor prognosis. Several chemotherapeutic agents have been evaluated in intensively pre-treated or cisplatin-refractory patients. Neither the anthracyclines nor vinorelbine, topotecan or biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%), with single patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two studies have evaluated gemcitabine in refractory germ-cell tumors and demonstrated a response rate of 17% (95% CI 7-28%) in 52 intensively pre-treated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem-cell transplantation. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m2 was tolerable, and hematological side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast and small-cell lung cancer, and oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may examine alternating treatment strategies in patients with poor-prognostic disease or as salvage treatment.

Treatment of patients with cisplatin-refractory testicular germ-cell cancer. German Testicular Cancer Study Group (GTCSG).

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ-cell tumors can be cured in 70% to 80% of patients. The combination of cisplatin, etoposide and bleomycine (PEB) is considered standard therapy. Patients refractory to cisplatin-based chemotherapy have a markedly poor prognosis. Several chemotherapeutic agents have been evaluated in intensively pre-treated or cisplatin-refractory patients. Neither the anthracyclines nor vinorelbine, topotecan or biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%), with single patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two studies have evaluated gemcitabine in refractory germ-cell tumors and demonstrated a response rate of 17% (95% CI 7-28%) in 52 intensively pre-treated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem-cell transplantation. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m2 was tolerable, and hematological side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast and small-cell lung cancer, and oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may examine alternating treatment strategies in patients with poor-prognostic disease or as salvage treatment.

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals.

The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis. A reference group of 37 men had a near In-Gaussian distribution for the absolute S-LD-1 catalytic concentration. The geometric mean was 76 U/l and an S-LD-1 >128 U/l (99.72 percentile, the decision limit) indicated a high risk of a relapse of TGCT. We have previously shown that an S-LD-1 >160 U/l (treatment limit) was associated with a suboptimal outcome from the treatment of metastatic TGCT. The maximum allowable analytical positive bias was 5 U/l, and the maximum allowable analytical negative bias was -32 U/l. The maximum allowable analytical coefficient of variation, CV(A), was 11% (approximately 14 U/l) at a bias = -5 U/l. For S-LD-1 measurements not corrected for hemolysis, the decision limit was 145 U/l, the maximum allowable negative bias -19 U/l, and CV(A) 8%(approximately 12 U/l). A routine correction for hemolysis had a large impact on the analytical quality specifications.

Nephroblastoma-like tumors in patients with testicular germ cell tumors.

Nephroblastoma-like tumors (NLTs) developed in metastatic sites in nine men with testicular germ cell tumors (GCTs). These tumors had a characteristic "triphasic" admixture of primitive tubular structures, sometimes with a glomeruloid pattern, blastema and stroma. Skeletal muscle differentiation was apparent in two cases. Specific neuroendocrine markers (synaptophysin and chromogranin A) were negative. All patients were treated by surgical excision. Six patients were alive with no evidence of disease from 4 to 12 years after diagnosis of GCT and NLT. One patient was alive with disease 6 years after diagnosis of GCT and 3 years after diagnosis of NLT. One man who also had metastatic primitive neuroectodermal tumor (PNET) had short survival, and one patient died of postoperative infection. We conclude that patients with testicular GCTs in whom NLTs develop in metastatic sites often experience prolonged survival. Surgical excision appears to be adequate treatment for NLT arising in metastatic testicular GCT in most patients. It is important to distinguish NLTs from PNETs in metastatic GCTs because of the more aggressive course and the frequently fatal outcome of the latter.

First-Line High-Dose Chemotherapy for ’Poor Risk’ Metastatic Non-Seminomatous Testicular Germ Cell Tumors

First-Line High-Dose Chemotherapy for ’Poor Risk’ Metastatic Non-Seminomatous Testicular Germ Cell Tumors