Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience.

Extragonadal germ cell tumours (EGCT) are uncommon, most frequently arise in the mediastinum and retroperitoneum and have variable responses to platinum-based chemotherapy. A retrospective analysis was performed on 38 patients with EGCT treated with cisplatin-based (CDDP) or carboplatin-based (CBDCA) chemotherapy between 1984 and 1998. Twenty-four patients had nonseminomatous germ cell tumours (NSGCT) and 14 seminoma. Twenty-two tumours arose in the mediastinum (13 nonseminomas, 9 seminomas) and 16 in the retroperitoneum (11 NSGCT, 5 seminomas). Initial surgery included complete resection in 1 patient, biopsy in 27 patients and debulking surgery in 10 patients. Complete response rates with chemotherapy +/- surgery were as follows: mediastinum 14 of 21 (66.66%) patients (8 of 12-75% NSGCT, 6 of 9-66.66% seminomas) and retroperitoneum 14 of 16 (87.5%) patients (9 of 11-81.81% NSGCT, 5 of 5-100% seminomas). One patient who underwent complete resection of a mediastinal malignant teratoma combined, received PVB chemotherapy on an adjuvant basis and remains alive and disease-free. Three additional seminoma patients who achieved partial response after chemotherapy remain alive and disease-free following mediastinal radiotherapy. All 14 patients with extragonadal seminomas remain alive with no evidence of disease at a median follow-up of 49 months (range 7-164), giving an overall survival of 100%. Nine of 13 (69.23%) patients with mediastinal NSGCT are long-term disease-free at a median follow-up of 43.5 months (range 7-152). Nine of 11 (81.81%) patients with retroperitoneal NSGCT remain alive and disease-free at a median follow-up of 56 months (range 14-110). Complete surgical resection of residual mass was undertaken in 10 patients (3 seminomas, 7 nonseminomas). The histology revealed necrosis/fibrosis in 6 patients (3 seminomas, 3 NSGCT) and viable cancer in 4 patients. Patients who had viable malignant cells in the resected specimens received two more courses of VelP chemotherapy. None of our patients had relapsed at the time of this analysis. None of our 6 patients who underwent testicular biopsy (1 patient) or orchiectomy (5 patients) due to suspicious ultrasound of the testis were found to have testicular tumour or fibrotic scar. In conclusion, this retrospective analysis showed significant responses in patients with either mediastinal or retroperitoneal NSGCT treated with CDDP- or CBDCA-based chemotherapy +/- surgery. All patients with extragonadal seminomas remain alive with no evidence of disease, regardless of the site at presentation.     

Germ cell tumours in uncorrected cryptorchid testis at Institute Rotary Cancer Hospital, New Delhi.

Twenty-four out of 164 (14%) adult patients with primary germ cell tumours of testis seen over the last 6 years at the Institute Rotary Cancer Hospital (IRCH) of the All India Institute of Medical Sciences (AIIMS), New Delhi, were found to have cryptorchidism. Only one patient had undergone correction. As a result the testes were intra-abdominal in the vast majority, and patients presented late. Twenty-two patients presented with stage IIb or more advanced disease. Twelve patients had seminoma and the others had mixed or non-seminomatous germ cell tumour (NSGCT), i.e. 50% each. The earlier patients were managed by initial resection followed by radiation and/or chemotherapy. As experience grew the seven patients who presented late were given initial chemotherapy followed by resection in those with residual tumours. The probability of overall survival was 0.65 at 36 months and, was not significantly different from survival in 114 patients with tumours of normally descended testis. Early orchipexy facilitates the detection, but whether it reduces the incidence of tumours is controversial. Uncorrected cryptorchidism is now rarely seen in the West, but in India and many other developing countries tumours of uncorrected cryptorchid testes continue to be seen.     

Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options

Between 1979 and 1996 303 men with stage I testicular germ cell tumours (120 seminoma and 183 non-seminomatous germ cell tumours (NSGCT)) were enrolled onto a programme of surveillance. In our institutions the frequency of computed tomography (CT) scans is reduced compared with other centres. For all 303 men, the median follow-up is 5.1 years (range: 0.1-21.7 years) and there have only been 3 deaths (1 from disease, 1 from neutropenic sepsis and 1 from secondary leukaemia). 52/183 (28%) patients with NSGCT and 18/120 (15%) patients with seminoma have relapsed. The relapse-free survival at 5 years is 82% for seminoma and 69% for NSGCT (Logrank P=0.004). All men who relapsed, except 1 man with NSGCT, were in the International Germ Cell Cancer Collaborative Group good or intermediate prognosis group at relapse. Half of the seminoma relapses presented with symptoms and 31% of the NSGCT relapses. The remaining relapses were detected serologically or radiologically by the surveillance programme. 5 men (2%) on surveillance, 3 with initial diagnosis of seminoma and 2 with NSGCT, have developed second contralateral testis tumours (all stage I seminomas). In a well motivated centre a policy of surveillance for stage I testicular germ cell tumours (both NSGCT and seminoma) is associated with a low mortality rate (3/303, 1%) and may have the advantage of sparing overtreatment with potentially toxic therapies in this group of young men.     

National survey of patterns of care for testis cancer

A national survey of testicular cancer documented recent trends in disease characteristics, treatment, and outcome, providing a basis for progress being achieved on a community basis. A long-term study of 3285 patients diagnosed between 1970 and 1975 was compared with a short-term study of 1887 patients diagnosed in 1983. An increase of the symptom of a lump in the testis from 23.1% to 31.2% and a mass as a sign of cancer from 44.5% to 53.8% suggests earlier detection of testis cancer by the patient and physician. Changes in the methods of diagnosis reflect the changing technology of tumor diagnosis. The 10-year survival rates for pathologic Stage I seminoma (82.6% of all seminomas) exceeded 96%. For pathologic Stage I nonseminomatous germ cell tumors (51.7% of all NSGCT), 10-year survival was 87.1%; whereas for Stage III (18.7% of all NSGCT) it was 22.1%. The impact of the important advances in chemotherapy is reflected in the increase of 1-year survival of Stage III NSGCT from 50.5% to 78.4%. Testis cancer can be cured in most patients.     

Results of treatment of non seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985

Between January 1981 and December 1985, 122 patients with non-seminomatous germ cell tumours (NSGT) were seen at a regional referral centre. Of these, a total of 98 patients received chemotherapy for metastatic disease. Treatment was given within collaborative EORTC Urology group studies, all of which involved cis-platin-containing schedules. Ninety patients had tumours of testicular origin, and their 2 year actuarial survival rate is 91%; 8 had tumours of extragonadal origin and their 2 year actuarial survival is 25%. Patients with testicular tumours were subdivided by volume of metastatic disease using the recommendations of the Testicular Cancer Subgroup of the MRC Urological Cancer Working Party and survival was significantly worse in the group with very large volume metastatic disease (VLVM, 57%) compared with the groups with large volume metastases (LVM, 100%) and small volume metastases (SVM, 98%). There were 31 patients with Stage I disease at presentation; of these 6 were treated by prophylactic abdominal radiotherapy and 25 were managed by a policy of surveillance only. Seven of these Stage I patients (23%) relapsed with metastatic disease (median 8 months); all have been successfully treated with chemotherapy. These data confirm that the majority of patients now presenting with metastatic NSGCT are curable with chemotherapy, but that a small proportion with very large volume metastases or extragonadal tumours require alternative chemotherapy schedules.     

Post-orchidectomy radiation therapy alone for patients with early stage non-seminomatous germ cell tumours of the testis

The aim of this study was to review the patterns of disease relapse and survival outcomes for patients treated postorchidectomy with radiotherapy for early stage (I and IIA) non-seminomatous germ cell tumors of the testis (NSGCT). The clinical records were reviewed of 117 men consecutively treated at the Queensland Radium Institute from 1960–90 (inclusive) for stage I or MA NSGCT. A total of 108 patients received radiotherapy to the para-aortic nodes and ipsilateral hemipelvis following orchidectomy; nine patients received radiotherapy to the para-aortic nodes and whole pelvis. Twenty-two of 99 (22.2%) stage I and eight of 18 (44.4%) stage MA patients relapsed following definitive radiotherapy. The 5 year overall and recurrence-free survivals were 84 and 75%, respectively. Factors associated with a significantly worse outcome included: (i) patients with stage IIA disease; (ii) the presence of undifferentiated elements in the operative specimen; (iii) a primary tumor < 5 cm size; and (iv) treatment given prior to 1979. Given the unsatisfactory recurrence rate following radiation therapy alone and the availability of cisplatin-based chemotherapy regimens, it is recommended that radiation therapy alone for patients with early stage NSGCT be abandoned in favour of other management strategies.     

Time trends in accuracy of classification of testicular tumours, with clinical and epidemiological implications.

Initial classifications of 1009 testicular tumours were reviewed as part of a population based survey of all testicular neoplasms in Victoria, Australia, between 1950 and 1978. All reviews were made by one of two pathologists at the Peter MacCallum Cancer Institute, using the system of the British Testicular Tumour Panel. Accuracy of diagnosis varied markedly over the time period and with pathological category. Seven cases were initially designated malignancies but were determined to be non-malignant conditions upon review. In each decade, review reduced the proportion of seminomas and increased the proportion of non-seminoma germ cell tumours (NSGCT) and non germ cell tumours. Reclassification resulted in changed age specific incidences of seminoma and NSGCT, most noticeably in 1950-59. Trends in age standardised incidence of seminoma and NSGCT were not affected by reclassification although the values were. The trend in age standardised incidence of non germ cell tumours was affected by reclassification. The implications of the changes in classification for epidemiological studies and clinical management are discussed.     

The management of stage I nonseminomatous testicular germ cell tumors

Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient's preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.     

Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution

BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar clinical and biologic characteristics, which are different from their testicular counterpart. The purpose of the current study was to review the authors' institutional experience of mediastinal GCT, emphasizing the clinical spectrum, time trends of treatment, and recent advances in therapeutic modalities for malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59 females) underwent surgical treatment for GCT, which accounted for 16.0% of the mediastinal tumors during the same period. There were 95 patients with mature teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years, respectively. RESULTS: Adult patients with mature teratomas were less symptomatic (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients received radical resection and/or chemoradiotherapy. However, all patients died due to disease progression, with a median survival period of 7.6 months. After 1986, six of eight patients received cisplatin-based chemotherapy, including three who received additional high-dose chemotherapy with a supporting peripheral blood stem cell transplantation until tumor markers normalized. Five patients who underwent salvage resection are currently disease free with a median survival period of 58.3 months. CONCLUSIONS: The institutional experience indicates the benign nature of mediastinal mature teratomas and the excellent prognosis for patients with seminomas after resection. An improved survival advantage was ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.     

The treatment of nonseminomatous testicular tumors: 15 years experience

Thirty-two patients with nonseminomatous germ cell tumors of the testis were treated at the Northern Israel Oncology Center during the years 1968-1983. The patients were divided into two groups. Group I included 18 patients treated from 1968 to 1976; in group II there were 14 patients treated with combination therapy containing cis-platinum in the years 1977 to 1983. The actuarial survival rate at 38 months from diagnosis is 47% in group I patients and 86% in group II patients. The development of modern radiological techniques, biochemical markers for accurate staging, and the use of cis-platinum-containing combination chemotherapy made this disease curable. New treatment modalities are needed for patients with bulky disease at presentation.     

Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer

TRA-1-60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA-1-60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included: Group 1, 34 patients with disseminated disease (24 nonseminomatous germ cell tumors [NSGCT] and 10 seminomatous germ cell tumors [SGCT]); this group of patients were followed during the course of chemotherapy with measurements of TRA-1-60, HCG and AFP; Group 2, 28 patients with Stage I NSGCT (22 with embryonal carcinoma [EC]-component and 6 without EC-component, median follow-up 15 months); and Group 3, 40 patients with Stage I pure SGCT (median follow-up 15 months). Seventy-eight percent of patients with disseminated EC-positive NSGCT had increased levels of TRA-1-60 before chemotherapy. After chemotherapy, levels of TRA-1-60 had dropped significantly (p < 0.01). Levels of TRA-1-60 did not normalize in 15% of NSGCT and 30% of SGCT patients after chemotherapy. This was not associated with recurrent disease. Approximately one-third of patients with Stage I NSGCT had increased values of TRA-1-60 during follow-up without having a relapse. Contrary to earlier reports TRA-1-60 is not at present useful as a tumor marker in patients with germ cell tumors. Although detecting a few early relapses the rate of false positive elevations in the tumor marker makes it unreliable in the clinical setting. Our study did confirm that elevated levels of TRA-1-60 were present in approximately 80% of patients with disseminated EC-positive NSGCT before start of chemotherapy and chemotherapy induced a significant decrease in levels of TRA-1-60. Thus, the TRA-1-60 antigen might still prove clinically useful provided that the reliability of the assay can be increased.     

Management of non-seminomatous germ cell tumors of the testes

Since the advent of cisplatin-based chemotherapy in the 1970s, testicular cancer has become a model for curable cancer. We review the current treatment options for non-seminomatous germ cell tumors (NSGCT) of the testes. Surveillance is considered to be the most widely accepted option for stage I NSGCT in Japan. Because of the high relapse rate of about 30% in this setting, the establishment of a risk-adapted treatment protocol is warranted in stage I NSGCT. In early stage II NSGCT, both the primary RPLND and the primary chemotherapy show equivalent cure rates. These options give different balances of toxicity; namely, ejaculation disorders and drug induced infertility. In the treatment for NSGCT with good prognosis, both three courses of BEP and four courses of etoposide and cisplatin are appropriate and standard chemotherapy regimens.     

Selection of treatment from a pathophysiological point of view. II: Studies on male urogenital tumors

Testicular cancer is divided pathologically into two categories; seminoma and non-seminomatous germ cell tumor (NSGCT). Seminoma is a radio-sensitive tumor, so that radiation has been mainly used for stages I and II. Stage III seminoma is treated in the same way as NSGCT. Several years ago stages I and II NSGCT were treated primarily by retroperitoneal lymph node dissection. These days, chemotherapy, such as PVB, or VAB-6 therapy, is adopted as the first choice of treatment, followed by surgical intervention to elucidate the remaining bulky mass if present. Stage III NSGCT is also managed by chemotherapy. By these procedures 70-90% CR of patients with NSGCT is obtained. Prostatic cancer has been treated mainly according to its stages. As for stage A cancer palliative therapy has been shown to yield good results. However, in the case of poorly-differentiated tumors, local irradiation with anti-androgenic treatment should be employed. Stage B cancer should be treated by radical surgery. Local lymph node dissection is usually indicated. In addition local irradiation and anti-androgenic therapy should be considered. Most stage C or D patients do well for a while with antiandrogenic therapy. Within two or three years, however, drug resistance ensues, recessitating a change in the therapeutic modality. Treatments of choice include in chemotherapy, radiotherapy, and others. Treatment of penile cancer involves chemotherapy with bleomycin and irradiation, which result in considerable improvement.     

Multimodality treatment of malignant germ cell tumours of the mediastinum

Of 15 patients with malignant germ cell tumours of the mediastinum, 9 patients had pure seminomas and 6 had non-seminomas. Resection was radical in only 4 non-seminomas, 1 of which was resected after chemotherapy; radiotherapy was delivered to all seminoma patients as sole therapy (2 patients) or as part of combined modality therapy. All patients with non-seminomatous tumours underwent chemotherapy (cisplatin-based combination). Therapy was generally well tolerated, but 1 seminoma patient died of sepsis. Chemotherapy achieved a 71% complete response rate in pure seminoma patients and a 33% complete response rate in non-seminoma patients. 53% of patients are alive and free of disease beyond 36 months from start of any treatment. Pure seminoma patients survived longer than non-seminoma patients (3 and 5 year survivals were 67% and 33%, respectively). Although cisplatin-based chemotherapy is highly effective in pure seminomas and also in non-seminomas, a better therapeutic approach is needed in non-seminomas.     

Late recurrence in 1263 men with testicular germ cell tumors. Multivariate analysis of risk factors and implications for management

BACKGROUND: Testicular germ cell tumors are highly curable. However, 10-30% of patients have recurrence after initial treatment. The time-course of recurrence has implications for the duration of follow-up. This study was undertaken to assess the risk and time-course of recurrence and to identify patients at higher risk of late recurrence. METHODS: The records of 1263 patients with primary testicular germ cell tumors presenting to the Royal Marsden Hospital between December 1979 and December 1993 were reviewed. In all, 255 episodes of recurrence were documented (including 44 patients with multiple recurrences) and used to calculate recurrence-free survivals. RESULTS: Fifty-three patients (15 seminomas; 38 nonseminomatous germ cell tumors [NSGCT]) had recurrence more than 2 years after initial presentation. A multivariate analysis of risk of recurrence after 2 years identified positive markers at presentation and the presence of differentiated teratomas in postchemotherapy surgical specimens as significant predictors. Very late recurrence (> 5 years) occurred mainly in patients with metastatic NSGCT (12 of 14 patients) with a 1% annual risk of recurrence between 5 and 10 years. Very late recurrence was also seen in one case of metastatic seminoma and one case of Stage I NSGCT managed by surveillance. Most late recurrences (n = 9) were detected at routine annual follow-up visits but five had recurrences with symptoms leading to an unscheduled clinic visit. CONCLUSION: Late recurrences are rare in patients with testicular germ cell tumors and follow-up to detect recurrence may not be needed after 5 years, except in those presenting with metastatic NSGCTs.     

Treatment of seminoma arising in cryptorchid testes.

We reviewed the clinical characteristics, treatment methods, and outcome of 26 patients presenting with seminoma arising in an undescended testis. The tumor-bearing testis was located in the iliac fossa in 17 patients and in the inguinal canal in nine. The most common presenting symptoms were pain or an enlarging mass. At diagnosis, the tumors tended to be relatively advanced, and 16 of 26 patients (62%) had nodal metastases. In addition to the paraaortic nodes, metastases were frequent to the ipsilateral iliac and inguinal nodes even in the absence of prior inguinal-scrotal surgery. Four patients had documented pelvic peritoneal tumor seeding. All patients received treatment in addition to resection of the primary tumor. Fifteen patients received radiotherapy only, 10 received chemotherapy only, and one received both modalities. At a median follow-up of 9.6 years, only one patient had relapsed. He was initially treated with radiation and after relapse was successfully salvaged with chemotherapy. The 5 and 10-year disease-free rate was 96%, and the 5 and 10-year survival rates were 92% and 79%, respectively. Appropriate treatment of seminoma arising in an undescended testis results in an excellent outcome equivalent to that observed for the more usual scrotal seminomas.     

Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.     

FDG-PET bei Keimzelltumoren

Positron emission tomography employing 18-fluorodeoxyglucose (FDG-PET) adds a metabolic functional dimension to the morphologic diagnostics of computed tomography (CT), with elevated glucose metabolism as a parameter of tumor activity. Because the sensitivity of FDG-PET is higher than that of CT for primary staging of germ cell tumors, FDG-PET could be used instead of CT. No data exist for its use in seminomas, but additional FDG-PET may be useful under certain conditions in nonseminomatous germ cell tumors (NSGCT) when the physician must decide between different therapeutic strategies such as “watch-and-wait” or adjuvant chemotherapy. Several studies have investigated the viability of residual masses in NSGCT. For special clinical questions, FDG-PET is able to offer additional information, which should be interpreted carefully within the clinical context because mature teratomas do not show elevated glucose metabolism and cannot be distinguished from necrotic masses. Moreover, inflammation or granulomatous diseases may increase false-positive results. In patients with seminomas and residual tumours, FDG-PET allows for therapeutic decisions; for example, resection can be avoided in residual masses larger than 3 cm, without FDG accumulation. Only limited data are available concerning the use of FDG-PET in patients with tumor marker elevation without morphological evidence of relapse or early prediction of therapeutic outcome, but FDG-PET may be helpful for further therapeutic decision making.     

A Scottish national audit of current patterns of management for patients with testicular non-seminomatous germ-cell tumours. The Scottish Radiological Society and the Scottish Committee of the Royal College of Radiologists.

A detailed casenote review was performed on all 65 patients registered with testicular non-seminomatous germ cell tumours (NSGCT) during 1989 under the Scottish Cancer Registration Scheme. Details of management at presentation and 2 years following diagnosis were recorded and analysed. In a small number of patients an unacceptable delay in diagnosis was noted. Variation was found in the frequency and type of investigations performed on patients placed on surveillance, types of chemotherapy regimens used and numbers of patients entered into trials. Three per cent of patients had a biopsy of the contralateral testis and 27% of patients defaulted from clinic attendance. Considerable variation in the management of testicular NSGCT in Scotland has been identified. The introduction of management guidelines should result in a more consistent approach to the care of these patients. Support, both financial and psychological, may reduce the unacceptable rate of default.     

Improving the outcome of salvage treatment for non-seminomatous germ cell tumours (NSGCT)

Between 1991-96, 41 patients were treated in this unit for relapsed non-seminomatous germ cell tumours (NSGCT). Twenty-eight patients had raised markers at relapse: 17 required salvage chemotherapy and post-chemotherapy surgery, 11 only chemotherapy. In addition 9 patients received high dose chemotherapy. Overall 16/28 patients (57%) requiring chemotherapy remain alive, 14 (50%) disease free. Of the 17 patients treated with chemotherapy and surgery: 12 remain alive, 10 (59%) with no evaluable disease. Only 4/11 (36%) patients treated with chemotherapy alone remain alive, all in complete remission (CR). For relapse with raised markers, univariate analysis suggests that less than CR to induction therapy, resulting in the presence of residual disease is the most important predictor of poor outcome (P<0.001). All of the 13 patients relapsing with normal markers remain alive, having been primarily treated surgically. Overall these results indicate an improving outlook for relapsed NSGCT.