Testicular transposition in children before scrotal external radiotherapy.

Testicular transposition (TT) before scrotal external radiotherapy (RT) is poorly reported in children with cancer, with only rare case reports published. TT surgical techniques, dosimetric parameters, and testicular functions are retrospectively reported in 12 children, median age 12.8 years, after scrotal RT for sarcomas. TT has low morbidity and allows a dramatic RT dose decrease in the healthy testicle. Endocrine functions seem preserved while more follow-up is needed to assess fertility. Though a rare situation, TT should be discussed in children and young adult cases when a scrotal high-dose RT is needed.

Lymphangioma Circumscriptum Post Radiotherapy for Penile Cancer Treated with CO2 Laser.

Lymphangioma circumscriptum (LC) is a rare, benign condition, predominantly characterized by the malformation of lymphatic skin vessels. Its onset may be congenital or due to secondary causes such as radiotherapy, infections, or surgical procedures. We present the case of a 55-year-old patient with a pathologic history of squamous cell carcinoma of the penis followed by radical penectomy. Due to metastasis to the locoregional lymph nodes, the entire affected area was subsequently treated with radiation therapy, receiving a total dose of 55.8 Gray. Eight years after this treatment, translucent vesicles filled with a clear liquid appeared on the scrotum. Histopathology confirmed the diagnosis of LC and therapy with CO2 laser was applied, resulting in a favorable outcome. LC of the scrotum may present a long-term radiotherapy-induced complication of this site. Our clinical experience showed that the CO2 laser was the therapy of choice as the vesicles entirely disappeared and healed as white scar-like lesions.

Thermoluminescence dosimetry of the dose received by scrotum and testes in radiotherapy of rectal cancer, compared to the point doses calculated by 3D-planning software.

PURPOSE: Radiation received by the testes in the course of radiotherapy for rectal cancer may cause oligospermia and azospermia. We sought to determine the dose to the scrotum and testes with thermoluminescence dosimetry (TLD), and compare it to the dose calculated by 3D planning software. METHODS: The TLDs were fixed to the scrotum in six points anteriorly and posteriorly in two fractions of radiotherapy. All patients received a 50-50.4 Gy total dose in prone position with 3D-planning. The average dose of TLD measurements was compared to the average of 6 relevant point doses calculated by the planning software. RESULTS: The mean scrotal dose of radiation in 33 patients as measured by TLD was 3.77 Gy (7.5% of the total prescribed dose), and the mean of point doses calculated by the planning software was 4.11 Gy (8.1% of the total dose), with no significant difference. A significant relationship was seen between the position of the inferior edge of the fields and the mean scrotal dose (P = .04). Also body mass index (BMI) was inversely related with the scrotal dose (P = .049). CONCLUSION: We found a dose of about 4 Gy received by the scrotum and testes from a total prescribed dose of 50 Gy in the radiotherapy of rectal carcinoma patients, with TLD measurements confirming testicular dose estimations by the planning software. This dose could be significantly harmful for spermatogenesis. Thus careful attention to the testicular dose in radiotherapy of rectal cancer for men desiring continued fertility is a necessity.

Low-level laser therapy to recovery testicular degeneration in rams: effects on seminal characteristics, scrotal temperature, plasma testosterone concentration, and testes histopathology.

The aim of this study was to investigate the efficiency of low-level laser therapy (LLLT) to recovery testicular degeneration in rams. In the first study, rams were induced to testicular degeneration by scrotal insulation, and then, they were treated using LLLT at 28 J/cm(2) (INS28) or 56 J/cm(2) (INS56) energy densities. Sperm kinetics, morphology, and membranes integrity as well as proportion of lumen area in seminiferous tubule were assessed. In the second study, rams were submitted or not to scrotal insulation and treated or not by the best protocol of LLLT defined by experiment 1 (INS28). In this study were evaluated sperm kinetics, morphology, membranes integrity, ROS production, and DNA integrity. Testosterone serum concentration and proportion of lumen area in seminiferous tubule were also analyzed. Insulation was effective in promoting sperm injuries in both experiments. Biostimulatory effect was observed in experiment 1: INS28 presented smaller proportion of lumen area (P = 0.0001) and less degeneration degree (P = 0.0002). However, in experiment 2, there was no difference between the groups (P = 0.17). In addition, LLLT did not improve sperm quality, and there was a decreasing for total and progressive motility (P = 0.02) and integrity of sperm membranes (P = 0.01) in LLLT-treated groups. Moreover, testosterone concentration was not improved by LLLT (P = 0.37). Stimulation of aerobic phosphorylation by LLLT may have led to a deregulated increase in ROS leading to sperm damages. Thus, LLLT at energy of 28 J/cm(2) (808 nm of wavelength and 30 mW of power output) can induce sperm damages and increase the quantity of cells in seminiferous tubule in rams.

Depletion of testis cell populations in pre-pubertal Bos indicus cattle by irradiation.

Recovery of spermatogenesis following a single dose of irradiation was evaluated in pre-pubertal Brahman bulls, after receiving a single dose of 3, 6, 9 or 12Gray (Gy) irradiation. Biopsy samples of testis tissue were collected and processed for immunohistology at various times following irradiation. Spermatogenic recovery was defined by the changes in tubule diameter, and absolute numbers of undifferentiated spermatogonia (PLZF positive cells) and Sertoli cells (GATA-4 positive cells) per tubule cross section. The effect of irradiation on the depletion of testicular cells was dose-dependent. Immunohistological results from both the 9 and 12Gy group showed degeneration of seminiferous tubules, compared with other doses and controls. From 2 weeks after the treatment, irradiation resulted in a significant and dramatic reduction in tubule diameter (up to 40%), number of undifferentiated spermatogonia (up to 90%) and Sertoli cells (up to 70%), which was sustained for up to 16 weeks post-irradiation in 9 and 12Gy groups (P<0.0001). However, a moderate depletion effect was observed in the 6Gy treatment groups, compared with 9 and 12Gy doses. The 6Gy treatment had significant effects on spermatogonia (up to 79% reduction) and Sertoli cell (30% reduction) numbers following irradiation (P<0.0001). In contrast, the 3Gy dose had no significant effect at either 3 or 5 weeks post-irradiation on tubule diameter, spermatogonia or Sertoli cells. In conclusion, the results from the current study suggest that treatment of recipient testes with a single dose of 6Gy irradiation can temporarily deplete spermatogonial cells in pre-pubertal Brahman bulls, whilst minimising the impact on Sertoli cells and tubule morphology.

Preparation of infertile male rabbits by local electron beam irradiation for intratesticular transplantation of autologous bone marrow stem cells.

PURPOSE: To explore an efficient and safe protocol for the preparation of infertile male rabbits from which bone marrow stem cells (BMSCs) could be isolated and cultured. METHODS: Autologous BMSCs could be used for intratesticular transplantation and male infertility research. For this model, various doses (e.g., 6, 8, 10, or 12 Gy) of electron beam irradiation from a linear accelerator were locally applied to the scrotum of 5-month-old male New Zealand white rabbits. The effects of irradiation were compared between treatment groups, and with age-matched normal controls. Both morphology and hollow ratios of seminiferous tubules (HRST) were examined two, four, six, eight and 12-weeks post-irradiation. RESULTS: The seminiferous epithelium showed varying degrees of damage in all treatment groups compared with unirradiated controls, yet Sertoli and Leydig cells appeared unaffected. A dose-dependent response in spermatogenesis was also observed. BMSCs that were isolated and cultured from rabbits of the normal control group and the 12 Gy treatment group were compared with respect to morphology and growth. Starting at 6 weeks, HRST of the 12 Gy-treatment group were stable, and were the highest among all the groups. BMSCs from rabbits treated with 12 Gy also exhibited similar growth as the control group. CONCLUSION: Local dose of 12 Gy to the testes of 5-month-old male New Zealand rabbits is a protocol with which to obtain autologous bone marrow stem cells.

Preparation of infertile male rabbits by local electron beam irradiation for intratesticular transplantation of autologous bone marrow stem cells

PURPOSE: To explore an efficient and safe protocol for the preparation of infertile male rabbits from which bone marrow stem cells (BMSCs) could be isolated and cultured. METHODS: Autologous BMSCs could be used for intratesticular transplantation and male infertility research. For this model, various doses (e.g., 6, 8, 10, or 12 Gy) of electron beam irradiation from a linear accelerator were locally applied to the scrotum of 5-month-old male New Zealand white rabbits. The effects of irradiation were compared between treatment groups, and with age-matched normal controls. Both morphology and hollow ratios of seminiferous tubules (HRST) were examined two, four, six, eight and 12-weeks post-irradiation. RESULTS: The seminiferous epithelium showed varying degrees of damage in all treatment groups compared with unirradiated controls, yet Sertoli and Leydig cells appeared unaffected. A dose-dependent response in spermatogenesis was also observed. BMSCs that were isolated and cultured from rabbits of the normal control group and the 12 Gy treatment group were compared with respect to morphology and growth. Starting at 6 weeks, HRST of the 12 Gy-treatment group were stable, and were the highest among all the groups. BMSCs from rabbits treated with 12 Gy also exhibited similar growth as the control group. CONCLUSION: Local dose of 12 Gy to the testes of 5-month-old male New Zealand rabbits is a protocol with which to obtain autologous bone marrow stem cells.

IMRT treatment of anal cancer with a scrotal shield.

The risk of sterility in males undergoing radiotherapy in the pelvic region indicates the use of a shielding device, which offers protection to the testes for patients wishing to maintain fertility. The use of such devices in the realm of intensity-modulated radiotherapy (IMRT) in the pelvic region can pose many obstacles during simulation, treatment planning, and delivery of radiotherapy. This work focuses on the development and execution of an IMRT plan for the treatment of anal cancer using a scrotal shielding device on a clinical patient. An IMRT plan was developed using Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA), using a wide array of gantry angles as well as fixed jaw and fluence editing techniques. When possible, the entire target volume was encompassed by the treatment field. When the beam was incident on the scrotal shield, the jaw was fixed to avoid the device and the collimator rotation optimized to irradiate as much of the target as possible. This technique maximizes genital sparing and allows minimal irradiation of the gonads. When this fixed-jaw technique was found to compromise adequate coverage of the target, manual fluence editing techniques were used to avoid the shielding device. Special procedures for simulation, imaging, and treatment verification were also developed. In vivo dosimetry was used to verify and ensure acceptable dose to the gonads. The combination of these techniques resulted in a highly conformal plan that spares organs and risk and avoids the genitals as well as entrance of primary radiation onto the shielding device.

The use of FDTD in establishing in vitro experimentation conditions representative of lifelike cell phone radiation on the spermatozoa.

Recent studies have shown that exposing human semen samples to cell phone radiation leads to a significant decline in sperm parameters. In daily living, a cell phone is usually kept in proximity to the groin, such as in a trouser pocket, separated from the testes by multiple layers of tissue. The aim of this study was to calculate the distance between cell phone and semen sample to set up an in vitro experiment that can mimic real life conditions (cell phone in trouser pocket separated by multiple tissue layers). For this reason, a computational model of scrotal tissues was designed by considering these separating layers, the results of which were used in a series of simulations using the Finite Difference Time Domain (FDTD) method. To provide an equivalent effect of multiple tissue layers, these results showed that the distance between a cell phone and semen sample should be 0.8 cm to 1.8 cm greater than the anticipated distance between a cell phone and the testes.

Antiapoptotic effect of L-carnitine on testicular irradiation in rats.

We evaluated the effects of L-carnitine on apoptosis of germ cells in the rat testis following irradiation. Male Wistar rats were divided into three groups. Control group received sham irradiation plus physiological saline. Radiotherapy group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiotherapy + L-carnitine group received scrotal irradiation plus 200 mg/kg intraperitoneally L-carnitine. Twenty-four hours post-irradiation, the rats were sacrificed and testes were harvested. Testicular damage was examined by light and electron microscopy, and germ cell apoptosis was determined by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) technique. Morphologically, examination of irradiated testis revealed presence of disorganization and desquamation of germinal cells and the reduction in sperm count in seminiferous tubule lumen. Under electron microscopy, the morphological signs of apoptosis were frequently detected in spermatogonia. Apoptotic spermatogonia showed the marginal condensation of chromatin onto the nuclear lamina, nucleus and cytoplasm shrinkage and still functioning cell organelles. TUNEL-positive cells were significantly more numerous in irradiated rats than in control rats. L-carnitine treatment significantly attenuated the radiation-induced morphological changes and germ cell apoptosis in the irradiated rat testis. In conclusion, these results suggested that L-carnitine supplementation during the radiotherapy may be beneficial for spermatogenesis following testicular irradiation by decreasing germ cell apoptosis.

Noninvasive laser vasectomy: preliminary ex vivo tissue studies.

BACKGROUND AND OBJECTIVES: Male sterilization (vasectomy) is more successful, safer, less expensive, and easier to perform than female sterilization (tubal ligation). However, female sterilization is more popular, primarily due to male fear of vasectomy complications (incision, bleeding, infection, and scrotal pain). The development of a completely noninvasive vasectomy technique may eliminate these concerns. MATERIALS AND METHODS: Ytterbium fiber laser radiation with a wavelength of 1,075 nm, average power of 11.7 W, 1-second pulse duration, 0.5 Hz pulse rate, and 3-mm-diameter spot was synchronized with cryogen cooling of the scrotal skin surface in canine tissue for a treatment time of 60 seconds. RESULTS: Vas thermal lesion dimensions measured 2.0+/-0.3 mm diameter by 3.0+/-0.9 mm length, without evidence of skin damage. The coagulated vas bursting pressure measured 295+/-72 mm Hg, significantly higher than typical vas ejaculation pressures of 136+/- 29 mm Hg. CONCLUSIONS: Noninvasive thermal coagulation and occlusion of the vas was produced in an ex vivo canine tissue model. However, chronic in vivo animal studies will be necessary to optimize the laser/cooling treatment parameters and confirm long-term vas occlusion with absence of sperm in the ejaculate, before clinical application.

Role of L-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study.

The present study, we hypothesized that L-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (gamma)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + L-carnitine group received scrotal gamma-irradiation plus 200 mg/kg i.p. L-carnitine. L-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of gamma-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, L-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy.

Evaluation of scrotal and testicular radiation doses for heterotopic ossification prophylaxis.

The majority of patients with heterotopic ossification are males with traumatic injuries in the hip/femur region. The testes, given their proximity, are exposed to scatter radiation, which has the potential to alter sperm count and morphology. In a prospective study, patients were treated with an 800-cGy dose of radiation without direct exposure of the testes/scrotum but with a testicular shield. Thermoluminescent dosimeters were placed inside and outside the shield. Mean dose inside and outside the shield was 10.2 and 20.2 cGy, respectively (sperm abnormalities have been reported with 15 cGy). Given our study results, young males should be counseled and should be treated with a testicular shield.

Shielding for scattered radiation to the testis during pelvic radiotherapy: is it worth?

OBJECTIVES: To assess the value of external shielding of the testis during pelvic radiotherapy. MATERIAL AND METHODS: Nineteen patients, receiving radiotherapy to the pelvis with the lower border of the field at the obturator foramen, were randomly selected. A 5 half value layer cerrobent shield was positioned at the inferior border of the field. The dose to the testis was measured with and without the shield. Observations were made regarding the reflex cremaster contraction and phantom measurements were done at different distances from the perineum. RESULTS: The mean radiation dose to the testis for patients receiving treatment with no shield was 7.4cGy (1.3) and it was 5.7cGy (-/+2.5) for patients with external shield, this difference was statistically significant by the paired t test p<0.0001. This accounted for a 22 % decrease in the dose received by the testis. The position of the testis with the contraction of the cremaster muscle and the dartos fascia after manipulation of the testis during diodes placement changed up to 3.5 cm (mean 1.5). Phantom measurements showed 37% increase in the dose with 2cm change in the position of the testis to the pelvic direction. CONCLUSION: External shield at the inferior border of the pelvic field is a simple, easy reproducible, convenient shielding method. Clam-shell scrotal shield is not free of drawbacks, but still its benefits overweigh its harms and should be used with caution.

Adult paratesticular malignant fibrous histiocytoma treated with surgery, systemic chemotherapy and postoperative adjuvant radiotherapy.

Paratesticular malignant fibrous histiocytoma is an extremely rare malignancy of the scrotum. This malignancy has rarely been described in the literature and scant information exists on the optimal management of this cancer. We present here a case of a 57-year-old man with a diagnosis of high-grade malignant fibrous histiocytoma of the left intrascrotal region who underwent radical orchiectomy, systemic chemotherapy and postoperative radiotherapy.

Seminoma of the testis: is scrotal shielding necessary when radiotherapy is limited to the para-aortic nodes?

PURPOSE: To evaluate the influence of different shielding conditions and field geometry on the scatter dose to the remaining testicle during postoperative radiotherapy (RT) in seminoma. MATERIALS AND METHODS: Testicular dose measurements were made with LiF thermoluminescent dosimeters (TLD) in 29 patients with stage I and IIA seminoma. The target volume consisted of para-aortic (PA) and para-aortic and homolateral iliac (PAI) lymph nodes in 14 and 15 patients, respectively. All patients had a scrotal shield as well as an additional block extending 7 cm inferiorly from the caudal field edge to shield the testicle from external scatter and collimator leakage. Doses with and without testicular blocks were measured for all patients. In seven patients treated exclusively to the PA region the gonadal dose was assessed according to four different shielding conditions: without any protection, with a gonadal shield alone, with the addition of an inferior field border block to the gonadal shield, and with the field border block alone. RESULTS: For patients treated with PAI fields the mean testicular doses per fraction were 3.89 cGy (S.D. +/- 1.44) and 1.48 cGy (S.D. +/- 0.51) without and with gonadal shielding, respectively (P-value < 0.001); the corresponding values for PA fields were 1.86 cGy (S.D. +/- 0.86) and 0.65 cGy (S.D. +/- 0.35). For the patients treated to the PA region and assessed according to the four different shielding conditions, the additional external block to the testicular shield did not reduce significantly the measured dose on the testis. CONCLUSIONS: These results suggest a benefit of gonadal shielding even in seminoma patients undergoing radiotherapy limited to the para-aortic region.

The management of spermatic cord sarcoma.

BACKGROUND: Between April 1963 and July 1991, 18 patients were treated for spermatic cord sarcoma. The histologic subtype distribution was: 7 leiomyosarcoma, 7 liposarcoma, 2 malignant fibrous histiocytoma, and 1 mesothelioma. METHODS: All patients underwent surgical resection: 16 radical orchiectomy and local excision. Nine were treated with orchiectomy alone, and 9 received adjuvant radiation. The radiation fields encompassed the ipsilateral iliac and inguinal lymph nodes, vas deferens, and hemiscrotum in 7 patients, and iliac and inguinal lymph nodes in 2 patients. RESULTS: The actuarial 5 and 8-year disease free survivals for the 18 patients were 77% and 58%, with an overall survival of 78% and 70%, respectively. The 5 and 8-year locoregional control rates were 82% and 61%. Five of 9 patients treated with surgery alone developed locoregional recurrence while none of the nine who had adjuvant radiation relapsed. The median follow-up for the irradiated group, however, was shorter (123 vs 63 months) and staging studies more complete. These potential biases are discussed. CONCLUSION: In this series, relapse was common after orchiectomy alone. Adjuvant radiation therapy may reduce the incidence of locoregional failure.

Radiotherapy in the management of epidemic Kaposi's sarcoma of the oral cavity, the eyelid and the genitals.

From January 1987 to December 1992, 420 patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma (EKS) were treated with radiotherapy at the oncology department in the Henri Mondor Hospital. Of these, 146 (34.7%) exhibited tumours at 186 sites; 35 were oral, 102 eyelid or conjunctival (ophthalmic), and 49 penile or scrotal (genital) sites. Most patients had received prior chemotherapy. Radiation therapy consisted of 4 MV or 45 kV X-rays, depending on tumor size and location. Doses ranged from 10 to 30 Gy, according to tumor response and toxicity. In oral lesions mucosal reactions were often observed after relatively low doses of radiotherapy. In 27 patients receiving 15 Gy, severe reactions were observed in 6 (22%), moderate reactions in 4 (15%) and mild reactions in 17 (63%). By contrast, irradiation of eyelid or conjunctival lesions and genital lesions, was well-tolerated. Treatment was generally successful in achieving good symptom palliation. Eyelid and conjunctival Kaposi's sarcoma seemed to be more radiosensitive when compared with cutaneous sites: a high objective remission rate (96%, 98/102) was observed at doses ranging from 10 to 20 Gy. Penile and scrotal lesions showed a good response to low dose radiation (complete response was scored in 34/49 patients (69.4%)). A meticulous evaluation of tolerance was necessary. Toxicity of oropharyngeal irradiation at relatively low doses is an argument for a restrictive use of this procedure in oral lesions.

Clinical thermoluminescence dosimetry: how do expectations and results compare?

Thermoluminescence dosimetry (TLD) for radiotherapy treatment verification is performed in the Prince of Wales Hospital in Sydney for a wide range of applications: (A) to determine the dose in difficult treatment geometries, (B) to record the dose to critical organs, and (C) to monitor special treatments such as total body irradiation (TBI). TLD measurements were performed with the aim to investigate cases where dose prediction is difficult and not as part of a routine verification procedure. We reviewed 1058 reports of TLD performed during the treatment of 502 patients between 1986 and 1991 to evaluate how the TLD results compare with the dose determined by the treatment plan. Reasons for possible discrepancies should be identified. In 19% of all investigated cases a discrepancy of more than 10% was found between expected and measured doses. The discrepancies could be divided into three groups: (1) errors made in the TLD determination or evaluation, such as placement errors of the TLD chips (21% of all discrepancies); (2) mistakes made during the patient set-up, such as insufficient shielding or inadequate patient immobilisation (30%); (3) inadequate treatment planning and dose calculation procedure, such as wrong inverse square law corrections or errors due to limitations of the two-dimensional treatment planning system used (41% of all). In 8% of all discrepancies the reason remained unclear. A number of changes to treatment plans and modalities (e.g. changed scrotal shield, modified bolus) were introduced due to TLD results. The increasing number of TLD requests per year attests to the value of TLD as a treatment verification method in clinical practice.

Consensus statement on the investigation and management of testicular seminoma 1989.

In the past 10 years, many developments have allowed us to understand more fully the natural history and routes of spread of testicular seminoma. The development of radiological tests such as CT scanning has allowed us to better assess the extent of disease. The availability of serum tumor markers AFP and beta HCG has facilitated the recognition of the presence of occult non-seminomatous elements. These developments plus the knowledge that seminoma is sensitive to cisplatin containing chemotherapy and that it is exquisitely sensitivity to radiation therapy resulted in further improvement in therapy. Overall we now expect 97 to 98% of patients will be cured of their disease. Currently, a number of issues in the management of seminoma remain controversial. These controversies however impact on very small proportion of patients with seminoma. Between 5 and 10% of patients have stage IID, III, or IV disease and 10 to 20% of these patients ie: 1 or 2% of the total population actually die from testicular seminoma. Thus it is for patients with advanced disease that we seek to define the nature of optimal chemotherapy, that is the most effective yet least toxic regimen. For those 1 or 2% of patients dying of seminoma we seek to identify prognostic factors to identify these patients and better treatments for them. Refinements in the application of radiation therapy for early stage disease, should allow some reduction in the morbidity of radiation without compromising control rates. Testicular seminoma its investigation and management, serves as a model for understanding other malignant processes and for orderly ways in which to refine the therapeutic ratio in the management of disease.