Testicular cancer and cryptorchidism.

The records of 273 patients with germ cell tumours of the testis referred between 1970 and July 1991 were reviewed. There were 25 (9%) black, 40 (14%) mixed race and 214 (77%) white patients. Histology showed seminoma in 53% and non-seminomatous and germ cell tumours in 47% of patients. Maldescent of the testis (MDT) was found in 30 patients--an incidence of 11% overall. MDT was present in 8 of 25 (32%) black, 7 of 40 (18%) mixed race and 15 of 214 (7%) white patients with testicular cancer. The incidence of MDT was statistically significantly higher in both black and mixed race patients compared with white patients. None of the black patients had undergone orchiopexy but 71% of mixed race and 87% of white patients had done so. This resulted in a different pattern of presentation in black compared with mixed race and white patients with MDT and testicular cancer. The mean age was 40 years for black, 32 years for mixed race and 33 years for white patients. Black patients presented with abdominal or inguinal tumours rather than scrotal tumours and they had an increased tendency to present with seminomas.     

THE SERUM PROLACTIN LEVEL IN TESTICULAR TUMOURS - A NEW TUMOUR MARKER?

Serum prolactin levels were elevated above the range seen in normal male subjects of 7 of 11 patients with non-seminomatous testicular tumours, particularly in patients with metastatic disease. In contrast, the mean prolactin level in patients with seminomas was not significantly different from normal, and only one of eight patients had a serum prolactin concentration beyond the normal range. In two subjects with non-seminomatous testicular tumours serial measurements of prolactin and chorlonic gonadotrophin showed a striking parallelism and accurately predicted clinical progress. Serum prolactin may be a useful additional tumour marker in patients with non-seminomatous testicular tumours.     

ELNATED LACTATE DEHYDROGENASE ISOENZYME I AS A TUMOUR MARKER IN PATIENTS WITH GERM CELL TESTICULAR TUMOURS

In a series of 50 patients with testicular tumours evaluated prior to orchidectomy, 12 out of 19 with pure seminoma and seven out of 31 with non-seminomatous or mixed seminomatous and non-seminomatous germ cell tumours had elevated plasma lactate dehydrogenase isoenzyme 1 concentrations. In contrast. seven of the 19 seminoma patients had elevated serum human chorionic gonadotrophin (hCG) concentrations and 25 of the 31 non-seminomatous and mixed seminomatous and non-seminomatous gem cell tumour patients had elevations of hCG and/or α-fetoprotein. Using these three markers, 12 out of 19 seminoma patients and 27 out of 31 non-seminomatous or mixed seminomatous and non-seminomatous tumour patients were positive for one or more of these tumour markers.     

Elevated lactate dehydrogenase isoenzyme 1 as a tumour marker in patients with germ cell testicular tumours

In a series of 50 patients with testicular tumours evaluated prior to orchidectomy, 12 out of 19 with pure seminoma and seven out of 31 with non-seminomatous or mixed seminomatous and non-seminomatous germ cell tumours had elevated plasma lactate dehydrogenase isoenzyme 1 concentrations. In contrast, seven of the 19 seminoma patients had elevated serum human chorionic gonadotrophin (hCG) concentrations and 25 of the 31 non-seminomatous and mixed seminomatous and non-seminomatous germ cell tumour patients had elevations of hCG and/or alpha-fetoprotein. Using these three markers, 12 out of 19 seminoma patients and 27 out of 31 non-seminomatous or mixed seminomatous and non-seminomatous tumour patients were positive for one or more of these tumour markers.     

The effect of patient's delay and doctor's delay in patients with malignant germ cell tumours

In 103 patients with malignant germ cell tumours the initial clinical diagnosis was incorrect in 45 (44%). The correct diagnosis was established within 2 months in only 31% of the patients, and delayed by more than 6 months in 27%.
Stage, distribution and survival were correlated with the histology, but not with the duration of symptoms or the patient's/doctor's delay.
Rapidly growing tumours often belonged to the non-seminornaious group where advanced tumour stages and low survival rates were more common than in the seminoma group.
The overall prognosis of patients with malignant germ cell tumours may be increased by an early diagnosis of testicular tumours in non-symptomatic patients, especially in men with possible risk factors (cryptorchidism, atrophic testis, antecedent contralateral testicular cancer).     

Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG)

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.     

HLA-antigen distribution in seminoma,HCG-positive seminoma and non-seminomatous tumours of the testis

Summary Histocompatibility antigens play a certain role in the development of testicular tumours. 151 patients with testicular cancer (86 non-seminomatous germ cell tumours—NSGCT-and 65 pure seminoma) were typed for the HLA-antigens of the A, B, C and DR locus. 24 patients of the pure seminoma group and 50 patients of the NSGCT group had an elevated serum HCG level preoperatively. The antigen DR-5 was elevated in the seminoma group whereas the incidence of B-13 was increased in the NSGCT group. In terms of antigen distribution HCG-positive seminoma resembles seminomatous tumours rather than NSGCT.     

Serum and tissue markers of testicular tumours

This article reviews the value of the tumour markers alpha-foetoprotein (AFP) and human chorionic gonadotrophin (hCG) in the management of patients with testicular germ-cell tumours, especially non-seminomatous tumours. Recent developments in their use, such as metabolic decay rate analysis, are discussed. Possible new markers for testicular cancer, particularly SP-1 and placental alkaline phosphatase, are reviewed.     

Is modified retroperitoneal lymph node dissection (MRLND) still feasible in the treatment of patients with clinical stage I non-seminomatous testicular cancer?

The results of treatment by means of modified RLND in 52 patients with clinical stage I non-seminomatous testicular cancer are presented. Retroperitoneal lymph node metastases were found in 15 patients (28.8%) with clinical stage I (CS-I) diagnosed prior to surgery. They received chemotherapy according to PVB schedule. Ejaculation disturbances persisted in 4 patients (7.7%). Relapses occurred in 4 patients (7.7%) from the group without lymph node metastases, and complete remission occurred after adjuvant PVB chemotherapy. All patients are still alive. Among the analysed factors which might favour development of metastases, only neoplastic invasion of the blood vessels of the primary tumour was statistically significant. In the authors’ opinion MRLND may still be used as a diagnostic and therapeutic method in clinical stage I non-seminomatous testicular cancer besides “watch policy” or primary chemotherapy.     

Single drug therapy in non-seminomatous germinal cell tumours of the testicle

The outcome for 84 patients in different stages of non-seminomatous germinal cell tumours of the testicle and treated with Mithramycin as a single agent has been evaluated. The survival rate in patients with advanced disease was lower than that obtained by more aggressive chemotherapy and, therefore, in these stages Mithramycin therapy is not recommended. On the other hand, the survival rate in patients with low-stage disease was superior to that in other series of patients subjected to bilateral lymphadenectomy without subsequent adjuvant chemotherapy. In the present study a unilateral gland dissection with preservation of a normal sexual function was performed in the vast majority of patients. Single-drug chemotherapy should preferably be used only as adjuvant treatment in low-stage non-seminomatous germinal cell testicular tumours.     

Morphology of testicular germ cell tumours in treated and untreated cryptorchidism

The histology of 75 testicular germ cell tumours in 73 patients with treated or untreated cryptorchidism was investigated in a group of 503 patients with testicular germ cell tumour and evaluated according to the WHO classification. The proportion of pure seminoma was associated with the height of the testis, being 87% in abdominal. 78% in inguinal and 50% in normally positioned testes. In patients operated upon for cryptorchidism, the current site of the testis seemed to be a more important determinant of this proportion than the original site. The proportion of pure seminoma which developed in testes after successful orchiopexy was equal to that in normally-descended testes (50%) and lower (39%) if orchiopexy had been performed before the age of 16 years. Similarly, among non-seminomas, a higher proportion of tumours containing teratoma tissue was found in cryptorchidism was successfully treated in childhood. It was concluded that a successful orchiopexy in childhood decreases especially the risk of seminoma.     

Significance of presence of teratomatous elements in the primary tumour of testicular cancer

To assess the tumour aggressiveness of teratoma, clinical records of patients with non-seminomatous germ cell testicular cancer were reviewed. Teratomatous elements were found in 57.8% of tumours. The rate of stage I tumours was lower in the teratoma-positive group than in the teratoma-negative group. Lymph node metastasis occurred more frequently than haematogenous metastasis in the teratoma-positive group. Tumour marker response in metastatic stage of teratoma-positive group was very excellent. Even if the radiographic response was not good, most patients were alive without disease after postchemotherapeutic salvage surgery. Furthermore, two patients with pure teratoma, who had tumour recurrence, were successfully treated with the multimodal therapy. Considering the smaller number of stage I patients in the teratoma-positive group than in the teratoma-negative group, the excellent overall response in the teratoma-positive group showed less aggressiveness of the tumour as a whole.     

Haemoglobin F levels in patients with testicular tumours

This study was designed to examine haemoglobin F levels prior to therapy in 39 patients with testicular tumours (10 seminoma, 29 non-seminomatous tumours) and 20 controls. HbF levels were significantly increased in the group with testicular tumours (1.66 +/- 0.12%) compared with normal controls (0.99 +/- 0.08%) (P less than 0.001). Non-seminomatous tumours had more pronounced levels than seminomas (P less than 0.001). No correlation was found between HbF level and stage of the disease. We suggest that HbF production could be significantly reactivated in adult patients with testicular tumours and may be a useful marker.     

Treatment decision for stage I non-seminomatous germ cell tumours based on the risk factor "vascular invasion".

Surveillance has become an alternative treatment modality for stage I non-seminomatous germ cell tumours with reported relapse rates of up to 30% in retrospective studies. Results obtained in our retrospective study showed vascular invasion in primary tumours to be the risk factor with the highest negative predictive value. Since January 1985 patients with stage I non-seminomatous germ cell tumours have been stratified by the presence or absence of vascular invasion in the primary tumour: those without vascular invasion (n = 26; group A) were subjected to a rigorous surveillance programme, while those with vascular invasion (n = 22; group B) were given 2 chemotherapy courses of bleomycin, etoposide and platinum in the hope of preventing progression. Relapse rates were 3.8% and 9% in groups A and B, respectively. The pooled relapse rate for both groups A and B (n = 48) was 6.2% (3/48). After a mean follow-up time of 36 months 95.8% (46/48) of the patients were without evidence of disease.     

Hodenkarzinom – gibt es eine Indikation für eine adjuvante oder neoadjuvante Systemtherapie?

Testicular cancer represents between 1 and 1.5% of male neoplasms and 5% of all urological tumours. There are indications for adjuvant or neoadjuvant systemic therapy in all stages of seminomatous and non-seminomatous testicular cancer. The treatment decision is strongly stage dependent. The primary treatment of choice for advanced disease is chemotherapy. In earlier stages a risk-adapted treatment should be used and besides chemotherapy, surveillance, radiotherapy and sometimes retroperitoneal lymph node dissection can be considered. In early stages it is important to reduce immediate adjuvant treatment in as many patients as possible to avoid acute and late toxicities. In advanced stages randomized trials have to clarify if there could be a better outcome with adding new agents or with high-dose chemotherapy for patients with “poor prognosis” and adverse features or patients with a chemoresistant relapse.     

Primary testicular seminoma in a patient with a history of extragonadal non-seminomatous germ cell carcinoma

Extragonadal germ cell carcinoma represents between 3% and 5% of all germ cell carcinomas. A metachronous primary germ cell carcinoma is exceedingly rare in these patients. We report the eighth case, which occurred in a 29-year-old man who presented with testicular seminoma 7 years after his initial presentation with extragonadal non-seminomatous germ cell carcinoma. The seven other patients also presented with extragonadal non-seminomatous germ cell carcinoma, followed subsequently by testicular seminoma in 6 patients and non-seminomatous germ cell carcinoma in the seventh. The mean time to presentation was 8 years. Although rare, this case emphasizes the need for long-term surveillance, including testicular evaluation of patients with a history of extragonadal germ cell carcinoma.     

Testicular cancer--is there an indication for adjuvant or neoadjuvant systemic therapy?

Testicular cancer represents between 1 and 1.5% of male neoplasms and 5% of all urological tumours. There are indications for adjuvant or neoadjuvant systemic therapy in all stages of seminomatous and non-seminomatous testicular cancer. The treatment decision is strongly stage dependent. The primary treatment of choice for advanced disease is chemotherapy. In earlier stages a risk-adapted treatment should be used and besides chemotherapy, surveillance, radiotherapy and sometimes retroperitoneal lymph node dissection can be considered. In early stages it is important to reduce immediate adjuvant treatment in as many patients as possible to avoid acute and late toxicities. In advanced stages randomized trials have to clarify if there could be a better outcome with adding new agents or with high-dose chemotherapy for patients with "poor prognosis" and adverse features or patients with a chemoresistant relapse.     

Bilateral synchronous testicular germ cell tumours in a patient with bilateral cryptorchidism

Bilateral testicular tumours are rare, and 80% of bilateral tumours are metachronous. The incidence of testicular tumours is high in cryptorchidism. Synchronous bilateral testicular tumours are rare, and bilateral synchronous testicular tumours in bilateral cryptorchidism extremely rare, probably not reported previously.     

BEP (bleomycin, etoposide, cisplatin) therapy for testicular tumors]

We describe our experience with BEP (bleomycin, etoposide, cisplatin) therapy as chemotherapy for testicular tumors in 11 patients. Eight were non-seminomatous testicular cancer patients and 3 were seminoma patients. Three of 8 non-seminomatous testicular cancer patients had no evident metastasis and BEP therapy was performed for prophylaxis of recurrence. Other 5 non-seminomatous testicular cancer patients and 3 seminoma patients had metastatic lesions and BEP therapy was performed to cure these metastatic lesions. Ten of our 11 patients are living and disease-free. One non-seminomatous testicular cancer patient who had brain, lung, eye and bladder metastases and had an extremely elevated human chorionic gonadotropin (hCG) level responded only partially and died later due to disease progression. Side effects in most patients were nausea, vomiting, alopecia and leucopenia and all these side effects were reversible. Neuromuscular toxicity such as paresthesia or abdominal cramp that is sometimes encountered in PVB (cisplatin, vinblastine, bleomycin) therapy was not seen in our patients. Our results support the concept that BEP therapy is better than PVB therapy as an initial chemotherapy for testicular tumors.     

The management of early stage non-seminomatous germ cell tumours of the testis: Edinburgh 1970-1981

This study describes the management of early stage non-seminomatous germ cell tumours of the testis in Edinburgh between 1970 and 1981. There were 69 patients in clinical Stage I and 22 patients in clinical Stage IIA. All were treated by orchiectomy and radiotherapy to the para-aortic nodes. Some of the patients with Stage IIA disease received additional therapy. The overall 5-year actuarial survival rate was 83%. In a group of 52 patients with Stage I disease who had had lymphography as part of their initial staging the 5-year actuarial survival rate was 94.2%. The overall relapse rate was 27/91 (29.7%). The relapse rate in State IIA disease was 11/22 (50%) and the 5-year actuarial survival rate was 64%. Patients with primary tumours beyond T1 had a significantly higher relapse rate than patients with T1 primary tumours: 10/20 (50%) and 13/52 (25%) respectively. The histology of the primary tumour did not have a statistically significant influence upon relapse rate.