Testicular Cancer Research: 2002-2006
     
Cancer. 2006 Aug 30; [Epub ahead of print]
Predictors of outcome in patients undergoing postchemotherapy retroperitoneal lymph node dissection for testicular cancer.
Spiess PE, Brown GA, Liu P, Tannir NM, Tu SM, Evans JG, Czerniak B, Kamat AM, Pisters LL.
Department of Urologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

BACKGROUND: The management of metastatic nonseminomatous germ cell tumors (NSGCT) frequently consists of systemic chemotherapy followed by retroperitoneal lymph node dissection (PC-RPLND). The aim of the present study was to evaluate the authors' PC-RPLND experience and identify predictors of outcome in these patients. METHODS: Between 1980 and 2003, 236 patients with clinical Stage IIA-III NSGCT underwent PC-RPLND. Their medical records were retrospectively reviewed for pertinent clinical and treatment-related outcomes. The 5-year disease-specific and recurrence-free survival was 85% and 75%, respectively, with the median length of follow-up after RPLND 45 months (6-250 months). RESULTS: The median age of patients at diagnosis was 28 years, with all patients receiving systemic chemotherapy (median of 5 cycles) before RPLND. On multivariate analysis, predictors of poorer disease-specific survival (DSS) included systemic symptoms at presentation (P = .05), elevated pre-RPLND serum alpha fetoprotein (AFP, P = .006) and beta-human chorionic gonadotropin (HCG, P = .004), postoperative complications (P = .03), and recurrence (P < .0001). Predictors of poorer recurrence-free survival (RFS) included advanced clinical stage (IIC-III, P = .001) and presence of viable tumor in the RPLND specimen (P = .03). A pre-RPLND serum AFP > 9 ng/mL and HCG > 4.1 mIU/mL were found to predict a worse DSS (P = .03 and .03, respectively). CONCLUSIONS: In patients undergoing PC-RPLND, preoperative tumor markers and the occurrence of postoperative complications or recurrence are predictive of poorer DSS. Advanced clinical stage and viable tumor in the surgical specimen predict worse RFS. Cancer 2006. (c) 2006 American Cancer Society.

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BJU Int. 2006 Aug;98(2):353-8.
Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure.
Geldart TR, Gale J, McKendrick J, Kirby J, Mead G.
Medical Oncology Unit, Southhampton University Hospitals NHS Trust, Southhampton, UK. trg@soton.ac.uk

OBJECTIVE: To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. PATIENTS AND METHODS: Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. RESULTS: In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26-217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9-184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. CONCLUSION: Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.

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BJU Int. 2006 Aug;98(2):349-52. Epub 2006 Apr 18.
Two cycles of cisplatin-based chemotherapy for low-volume retroperitoneal stage II nonseminomatous germ cell tumours.
Steiner H, Muller T, Gozzi C, Akkad T, Bartsch G, Berger AP.
Department of Urology, University of Innsbruck, Austria. hannes.steiner@uibk.ac.at

OBJECTIVE: To evaluate the oncological efficacy of reducing cisplatin-based chemotherapy to two cycles in patients with low-volume retroperitoneal stage II nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: From October 1988 until January 2004, two cycles of cisplatin-based chemotherapy were administered in 59 patients with low-volume retroperitoneal clinical stage II NSGCT (retroperitoneal mass of <5 cm in diameter). Regardless of remission detected on computed tomography, 6 weeks after chemotherapy the patients had a retroperitoneal lymph node dissection (RPLND) to assess residual active tumour or mature teratoma (open modified bilateral RPLND until 1992, then laparoscopic unilateral template RPLND). RESULTS: The chemotherapy was effective, as no active tumour was found in any of RPLND specimens. Mature teratoma was present in lymphatic tissue in 23 of 59 patients (39%). In one patient there was a pulmonary recurrence, successfully treated with cisplatin-based salvage chemotherapy. One patient died from an accident but with no evidence of tumour, and 56 patients remained free of disease at a mean follow-up of 98.6 months. No patient died from disease. All patients had antegrade ejaculation after laparoscopic RPLND, as did 89% after open RPLND. CONCLUSION: In this pilot study, the oncological efficacy of two cycles of cisplatin-based chemotherapy was favourable, but this approach still cannot be recommended as a standard treatment for patients with low-volume retroperitoneal stage II disease. RPLND after chemotherapy has diagnostic (detecting active tumour) and therapeutic (removing mature teratoma) value and can be done laparoscopically. Based on the present results a prospective randomized trial seems reasonable.

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BJU Int. 2006 Jul;98(1):67-9.
Treating stage I nonseminomatous germ cell tumours with a single cycle of chemotherapy.
Gilbert DC, Norman AR, Nicholl J, Dearnaley DP, Horwich A, Huddart RA.
Academic Unit of Radiotherapy & Oncology, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.

OBJECTIVE: To estimate the rate of relapse in men with stage I nonseminomatous germ cell tumours (NSGCT) of the testis treated with one cycle of chemotherapy instead of the usual two cycles. PATIENTS AND METHODS: Between 1992 and 1996, 22 men with stage I NSGCT who had normalized tumour markers after orchidectomy and negative findings on computed tomography, and who were at moderate risk of relapse, were treated with one cycle of platinum-containing chemotherapy (bleomycin and etoposide with either cisplatin or carboplatin). RESULTS: At a median follow-up of 10.2 years, none of the patients have relapsed with malignant GCTs. CONCLUSION: The results after one cycle of chemotherapy are no worse than after two cycles. The present study needs to be replicated in a larger cohort of patients to define the relapse risk more accurately. This approach is soon to be tested in a large multicentre trial randomizing patients between one and two cycles.

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Urology. 2006 Jul;68(1):154-60. Epub 2006 Jul 3.
Quality of life after laparoscopic and open retroperitoneal lymph node dissection in clinical Stage I nonseminomatous germ cell tumor: a comparison study.
Poulakis V, Skriapas K, de Vries R, Dillenburg W, Ferakis N, Witzsch U, Becht E.
Department of Urology, Northwest Hospital, Stiftung Hospital zum Heiligen Geist, Frankfurt am Main, Germany.

OBJECTIVES: To compare the postoperative quality of life (QOL) and reconvalescence in patients with clinical Stage I nonseminomatous germ cell tumor (NSGCT) after laparoscopic retroperitoneal lymph node dissection (L-RPLND) and the open procedure (O-RPLND). METHODS: Twenty-one patients with NSGCT who underwent transperitoneal L-RPLND were matched and compared with 29 patients who underwent O-RPLND. The operative, QOL, and recovery data and complications and cure rates were analyzed for both groups. RESULTS: The mean follow-up time for the L-RPLND and O-RPLND groups was 14 months (range 6 to 20) and 26 months (range 8 to 38), respectively. No major complication requiring open surgical revision or prolongation of hospitalization was observed intraoperatively or postoperatively in either group. However, the early and late minor postoperative complications were significantly greater in the O-RPLND group than in the L-RPLND group (P <0.001). The L-RPLND patients had a significantly shorter hospitalization, greater QOL scores, and a faster return to normal activities than did the O-RPLND patients (all P <0.001). CONCLUSIONS: L-RPLND for patients with clinical Stage I NSGCT is a safe and efficacious procedure, with a faster reconvalescence and greater postoperative QOL than after O-RPLND.

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Can J Urol. 2006 Jun;13 Suppl 3:30-6.
Does prolonging the time to testicular cancer surgery impact long-term cancer control: a systematic review of the literature.
Bell D, Morash C, Dranitsaris G, Izawa J, Short T, Klotz LH, Fleshner N; Canadian surgical wait times (SWAT) initiative.
Dalhousie University, Halifax, Nova Scotia, Canada.

BACKGROUND: The wait times for urological cancer surgeries in Canada are beyond those recommended by the Canadian Association of Surgical Oncology. Prolonged wait times have a negative impact on patient quality of life but the effect on long-term cancer control is controversial. We conducted a systematic review of the testicular cancer literature to examine the best available evidence addressing the following key questions: What is the reported time interval for testicular cancer patients from the decision to operate until the day of testicular cancer surgery? Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e. recurrence free survival, overall survival)? METHODS: A structured literature search of Medline, Pubmed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Database of Abstracts of Reviews of Effects, Healthstar and Google Scholar from January 1980 to September 2005 was conducted for published epidemiological studies and international guidelines/consensus documents that evaluated surgical wait times for testicular cancer. Data extracted from eligible studies included median time to diagnosis and to testicular cancer surgery. RESULTS: Five studies evaluating different components of wait times (e.g. delay in diagnosis, delay in orchiectomy) in testicular cancer patients were identified, four of which measured the impact of prolonged delays on relapse free and overall survival. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. In one study from the United Kingdom, median wait time was 30 days from general practitioner referral to surgery and 4 days from diagnosis to surgery. No Canadian studies specific to testicular cancer were identified. The association between surgical delay and clinical outcomes remained controversial where only one of five epidemiological studies reported an association between treatment delay and relapse free and overall survival CONCLUSIONS: Even though the association between surgical delay and disease related clinical outcomes remains controversial, there is an ongoing concern that the psychological impact of prolonged waiting for urological cancer surgery could negatively impact patient outcomes. Additional research is needed to identify the current wait times for testicular cancer in Canada and to develop guidelines and recommendations on what appropriate wait times should be. To address these important issues, the surgical wait times (SWAT) initiative is mandated to provide the necessary guidance and recommendations to the federal and provincial governments. Through a partnership between the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of cancer patients.

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Drugs. 2006;66(5):641-59.
Advances in the treatment of testicular cancer.
Kopp HG, Kuczyk M, Classen J, Stenzl A, Kanz L, Mayer F, Bamberg M, Hartmann JT.
Department of Medical Oncology, Medical Center II, Hematology, Rheumatology, Pneumology and Immunology, South West German Cancer Center, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.

Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm". Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%. Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients. In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT.This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%). However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied. For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.

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Urologe A. 2006 May;45(5):600-604.
[Chemotherapy of testicular cancer.]
[Article in German]
Krege S, Hartmann JT, Rubben H.
Urologische Klinik, Universitat, Hufelandstrasse 55, 45122, Essen, susanne.krege@uni-essen.de.

Platinum-based polychemotherapy has increased the cure rate in testicular cancer dramatically: at first, chemotherapy was mainly used in advanced disease. Recently it has also become common in low-stage disease, though other therapeutic options are equivalent. Risk factors might help to find the right decision.The success of treatment in patients with metastatic disease results from the combination of chemotherapy and secondary surgery. High-dose chemotherapy for patients with poor prognosis or recurrent disease is being evaluated in clinical trials. Concerning the success in these stages prognostic factors are of special importance. Patients with advanced-stage nonseminoma need residual tumor resection after chemotherapy if no complete remission could be achieved.The therapist should be aware of the indication for and schedule of chemotherapy, its side effects, and supportive care.

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Urologe A. 2006 Apr 13; [Epub ahead of print]
[Chemotherapy of testicular cancer.]
[Article in German]
Krege S, Hartmann JT, Rubben H.
Urologische Klinik, Universitat, Hufelandstrasse 55, 45122, Essen, susanne.krege@uni-essen.de.

Platinum-based polychemotherapy has increased the cure rate in testicular cancer dramatically: at first, chemotherapy was mainly used in advanced disease. Recently it has also become common in low-stage disease, though other therapeutic options are equivalent. Risk factors might help to find the right decision.The success of treatment in patients with metastatic disease results from the combination of chemotherapy and secondary surgery. High-dose chemotherapy for patients with poor prognosis or recurrent disease is being evaluated in clinical trials. Concerning the success in these stages prognostic factors are of special importance. Patients with advanced-stage nonseminoma need residual tumor resection after chemotherapy if no complete remission could be achieved.The therapist should be aware of the indication for and schedule of chemotherapy, its side effects, and supportive care.

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Urol Oncol. 2006 Mar-Apr;24(2):172-3.
Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion.
Stephenson AJ, Bosl GJ, Bajorin DF, Stasi J, Motzer RJ, Sheinfeld J, Rowland RG.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers and Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY.

PURPOSE: The outcome after primary retroperitoneal lymph node dissection (RPLND) was analyzed in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with embryonal carcinoma predominance (ECP) or lymphovascular invasion (LVI). MATERIALS AND METHODS: Between 1989 and 2002, 267 patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer, and ECP and/or LVI underwent RPLND. Patient information was obtained from a prospective database. Median followup was 53 months. RESULTS: Overall 42% of patients had pathological stage (PS) II disease, of whom 54% had low volume (PN1) disease and 16% had retroperitoneal teratoma. The 5-year progression-free probability was 90% overall, 90% for PS I and 86% for PN1. All patients with relapse were continuously free of disease following standard chemotherapy with or without resection of residual masses and the 10-year actuarial overall survival was 100%. When adjuvant chemotherapy was restricted to patients with PN2 disease, the estimated 5-year relapse rate was 9% and an estimated 72% of patients avoided chemotherapy. CONCLUSIONS: The low risk of systemic relapse in patients with PS I and PN1 after RPLND alone combined with the 16% incidence of retroperitoneal teratoma and the favorable morbidity profile supports RPLND over primary chemotherapy for the treatment of patients with low stage disease with ECP and/or LVI who are not candidates for surveillance. An estimated 72% of patients are spared the potential toxicity of chemotherapy if adjuvant therapy is restricted to patients with PN2. After primary RPLND and selective adjuvant chemotherapy late recurrence is distinctly uncommon and long-term cancer control is anticipated in essentially all patients.

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Drugs. 2006;66(5):641-59.
Advances in the treatment of testicular cancer.
Kopp HG, Kuczyk M, Classen J, Stenzl A, Kanz L, Mayer F, Bamberg M, Hartmann JT.
Department of Medical Oncology, Medical Center II, Hematology, Rheumatology, Pneumology and Immunology, South West German Cancer Center, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.

Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm". Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%. Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients. In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT.This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%). However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied. For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.

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World J Urol. 2006 Mar 8; [Epub ahead of print]
Long-term outcome of retroperitoneal lymph node dissection in the management of testis cancer.
Beck SD, Foster RS.
Department of Urology, Indiana Cancer Pavilion, Indiana University Medical School, 535 N. Barnhill Drive, Suite 420, Indianapolis, IN, 46202, USA, stdbeck@iupui.edu.

In low volume testicular cancer, (clinical stage A/B1) retroperitoneal lymph node dissection has maintained its therapeutic benefit while minimizing morbidity with the reduction of the surgical template from a full bilateral dissection to a unilateral nerve-sparring surgery. The optimal treatment for low stage disease is largely patient driven with surgery and surveillance considered the primary treatment modalities. In the post chemotherapy population, patients with complete radiographic resolution of retroperitoneal disease are observed at Indiana University as the relapse rate in this population is ~5%. Residual masses after chemotherapy should be resected. A modified post chemotherapy dissection is adequate in low volume disease restricted to the primary landing zone of the affected testicle. In chemo-refractory disease, aggressive surgery provides a 5 year survival of 31% for patients with active cancer. Excluding chemo-naive patients, late relapse disease is managed surgically with 50% being cured of disease.

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Lancet. 2006 Mar 4;367(9512):754-65.
Testicular germ-cell cancer.
Horwich A, Shipley J, Huddart R.
Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK. alan.horwich@icr.ac.uk

Testicular germ-cell tumours (TGCTs) represent the model of a curable malignancy; sensitive tumour markers, accurate prognostic classification, logical series of management trials, and high cure rates in both seminomas and non-seminomas have enabled a framework of effective cancer therapy. Understanding the molecular biology of TGCT could help improve treatment of other cancers. The typical presentation in young adults means that issues of long-term toxicity become especially important in judging appropriate management. A focus of recent developments has been to tailor aggressiveness of treatment to the severity of the prognosis. Recent changes affect the most common subtypes and include the reduction of chemotherapy for patients who have metastastic non-seminomas and a good prognosis, and alternatives to adjuvant radiotherapy in stage I seminomas. We summarise advances in the understanding and management of TGCT during the past decade.

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Gan To Kagaku Ryoho. 2006 Feb;33(2):183-7.
[Progress in therapy for testicular tumors]
[Article in Japanese]
Mizutani Y, Nakamura T, Nomoto T, Kawauchi A, Miki T.
Dept. of Urology, Kyoto Prefectural University of Medicine.

Approximately 80% of patients with metastatic testicular tumors are cured by cisplatin-containing chemotherapy and surgery. However, the remaining 20% of patients with advanced testicular tumors can not be cured at present. Thus, therapy for these testicular tumors infractory to treatment is the most important issue. Recently, chemotherapy for such tumors is developing, especially salvage chemotherapy using novel anticancer agents(paclitaxel, gemcitabine,irinotecan, docetaxel, oxaliplatin, etc) and high-dose anticancer drugs. Some of the new modalities are very attractive. In this article, we reviewed mainly these new forms of chemotherapy for testicular tumors.

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J Urol. 2005 Dec;174(6):2209-13, discussion 2213.
Minimizing treatment without compromising cure with primary surveillance for clinical stage I embryonal predominant nonseminomatous testicular cancer: a population based analysis from British Columbia.
Al-Tourah AJ, Murray N, Coppin C, Kollmannsberger C, Man A, Chi KN.
Vancouver Cancer Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada.

PURPOSE: We evaluated the outcome of patients with embryonal carcinoma predominant (ECP) clinical stage (CS) I nonseminomatous testicular germ cell tumors (NSGCT) treated with primary surveillance or primary retroperitoneal lymph node dissection (RPLND). MATERIALS AND METHODS: This study was a retrospective evaluation of the pathology, use of chemotherapy, surgery and outcomes in all patients with CS I NSGCT who were diagnosed within the province of British Columbia between 1990 and 2000. RESULTS: A total of 205 patients were identified, of whom 107 (52%) had ECP disease. Of these patients 72 (67%) underwent primary surveillance, 32 (33%) underwent primary RPLND and 3 refused treatment. Median followup was 4 years (range 1 to 10). In the primary surveillance group 24 patients (33%) had relapse and all were treated initially with chemotherapy with 6 also requiring RPLND. The remaining 48 patients (67%) in the surveillance group were cured of disease with orchiectomy alone. In the primary RPLND group 18 patients (56%) had pathological stage I disease and 14 (44%) had pathological stage II disease. In the primary RPLND group 15 patients (46%) required chemotherapy with 11 (34%) receiving adjuvant chemotherapy and 4 receiving chemotherapy for post-RPLND relapse. No deaths from ECP testicular cancer occurred in either group. The 4-year chemotherapy-free survival rate was 65% in the surveillance group vs 50% in the RPLND group (p = 0.2). CONCLUSIONS: For appropriately selected patients with CS I ECP NSGCT, primary surveillance results in fewer therapeutic interventions compared to RPLND without compromising the probability of cure.

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Br J Cancer. 2005 Nov 28;93(11):1209-14.
Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948).
Fossa SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group.
Department of Oncology, Norwegian Radium Hospital, University of Oslo, Oslo, Norway. s.d.fossa@klinmed.uio.no

New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9-79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7-66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5-91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6-93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.

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Ann Urol (Paris). 2005 Oct;39(5):159-69.
[Testicular germ-cell tumour: diagnosis and treatment]
[Article in French]
Houlgatte A, Bauduceau O.
Clinique urologique, hopital d'instruction des Armees du Val de Grace, 74, boulevard de Port-Royal, 75005 Paris, France. houlgatte.urovdg@free.fr

Among germ cell tumours, seminomas hold a particular status related to their radio-sensitivity. Although radiotherapy remains the best treatment for Localized tumours of stage 1, in some cases, surveillance or chemotherapy may presently be considered as alternative therapies. Due to Long-term radiotherapy-related adverse effects, in particular the risk of second non-germ malignancies or cardiac morbidity, both dose and irradiation field are reduced in case of lymphatic retroperitoneal extension. Chemotherapy is the preferential treatment in more advanced stages, either with retroperitoneal bulky disease or with metastatic extension. Its efficacy allows Limiting surgical indications on residual masses, relying partly on the follow-up data of positron emission transaxial tomography assessment.

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ScientificWorldJournal. 2005 Oct 16;5:852-67.
Changing management of clinical low-stage testicular cancer.
Gilligan T.
Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, Ohio, USA. GILLIGT@CCF.ORG

Stage I and II testicular germ cell tumors (GCTs) are almost always cured with appropriate treatment and most ongoing research regarding these tumors focuses on minimizing treatment toxicity. The management of clinical stage I testicular GCTs has grown more complicated due to the emergence of a brief course of chemotherapy as an additional treatment option for stage I seminomas and stage I nonseminomas. In addition, growing concern about radiation-induced cancers and other late toxicity has dulled enthusiasm for radiotherapy as a treatment for stage I seminomas. However, recent randomized trials have shown that radiotherapy doses and field sizes can be lowered without compromising cure rates and it is possible that this reduction in radiation exposure will reduce the rate of secondary cancers. At this point in history, stage I patients have three treatment options following radical orchiectomy: adjuvant (sometimes called "primary") chemotherapy (carboplatin for seminomas and the combined regimen of bleomycin, etoposide, and cisplatin for nonseminomas), surveillance, and either retroperitoneal lymph node dissection (for nonseminomas) or radiotherapy (for pure seminomas). Clinical studies have made it possible to identify subgroups of patients at high and low risk for relapse and this has made it possible to tailor treatment decisions to the individual patient's postorchiectomy relapse risk.

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Clin Oncol (R Coll Radiol). 2005 Oct;17(7):539-42.
The management strategies for stage I seminoma.
Josefsen D, Fossa S.
Department of Oncology, Rikshospitalet-Radiumhospitalet Trust, Oslo, Norway. dag.josefsen@radiumhospitalet.no

About 80% of men with seminomatous testicular germ-cell cancer are diagnosed with stage I disease. For many years, the standard treatment for this patient group has been radiation to para-aortic and iliacal lymph nodes at the same side as the orchiectomy. However, iliac radiotherapy is unnecessary in patients without prior inguinal or scrotal surgery. Furthermore, in recent years, other treatment modalities for this patient group have evolved. The use of single-agent carboplatin has shown promising results, similar to the effects obtained by radiotherapy. In addition, surveillance after primary orchiectomy with no additional treatment is found to be a safe follow-up for many of these patients. On the basis of new knowledge about primary tumour risk factors, it is now possible to identify patients at a particular high risk of relapse (rete testis invasion, primary tumour size > 4 cm, or both). This will be a helpful tool to identify patients who can be safely included into a surveillance strategy, and those who could have adjuvant treatment. The final decision about treatment will depend on risk factors, capacity of the healthcare service to carry out frequent follow-up examinations and the patient's own preferences. In this paper, we will discuss advantages and disadvantages of the various treatment options in the management of stage I seminoma.

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Ann Oncol. 2005 Oct 27; [Epub ahead of print]
Single agent carboplatin for CS IIA/B testicular seminoma. A phase II study of the German Testicular Cancer Study Group (GTCSG).
Krege S, Boergermann C, Baschek R, Hinke A, Pottek T, Kliesch S, Dieckmann KP, Albers P, Knutzen B, Weinknecht S, Schmoll HJ, Beyer J, Ruebben H.
University/Medical School, Urology, Essen, Germany.

BACKGROUND: The aim was to investigate the use of single agent carboplatin in patients with seminoma stage IIA/B. PATIENTS AND METHODS: In a prospective phase II trial, single agent carboplatin at a dose of AUC 7 mg.min/ml every 4 weeks for three cycles in stage IIA (n = 51) or four cycles in stage IIB (n = 57) was given to 108 patients with previously untreated seminoma stage IIA/B. Patients with residual masses of >/=3 cm were scheduled to receive secondary surgery. RESULTS: A complete response (CR) was achieved by 88/108 (81%) patients, 17/108 (16%) achieved a partial response (PR), two of 108 (2%) showed no change, and one patient progressed. In all patients with PR the residual disease was </=3 cm; yet in two of 17 patients with PR, in two of two patients with NC and in one patient with disease progression residual tumor resection was performed demonstrating vital seminoma. Toxicity was acceptable with grades 3 and 4 myelosuppression, nausea and vomiting in less than 10% of patients each. After a median follow-up of 28 months (range 1-68 months) 14/108 (13%) patients relapsed, all after having achieved a CR. All relapses occurred in the retroperitoneum. One patient died from an unrelated cause. The overall failure rate was 19/108 patients (18%). The overall and disease specific survival was 99% and 100%, respectively. CONCLUSIONS: Four cycles of single agent carboplatin AUC 7 do not safely eradicate retroperitoneal metastases in patients with stage IIA/B seminoma.

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Clin Oncol (R Coll Radiol). 2005 Oct;17(7):543-52.
The management of poor-prognosis, non-seminomatous germ-cell tumours.
Sirohi B, Huddart R.
The Academic Unit of Radiotherapy and Oncology, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.

Despite a high cure rate in men with testicular cancer, some men in the poor-prognosis group have a less favourable outcome. Poor-prognosis non-seminomatous germ-cell tumours (NSGCT) are defined as those with high tumour markers, non-pulmonary visceral metastases or a mediastinal primary site at presentation. When treated with standard chemotherapy regimens, such as bleomycin, etoposide and cisplatin (BEP), cure rates of less than 50% have been achieved in an international pooled analysis. Some strategies aimed at improving results include the use of multi-agent regimens (e.g. POMB/ACE), intensive-induction chemotherapy (e.g. CBOP/BEP), new chemotherapy drugs, such as ifosfamide, gemcitabine, oxaliplatin, paclitaxel, high-dose chemotherapy, including autotransplantation. To date, no schedule has been proven to be better than standard BEP in randomised trials. We will review the published data relating to first-line and salvage treatment of poor-prognosis NSGCT. To advance the management of this disease, physicians treating poor-prognosis disease are urged to support multi-centre trials, such as the recently launched MRC TE23 study comparing BEP and CBOP/BEP.

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J Endourol. 2005 Sep;19(7):823-6.
Laparoscopic retroperitoneal lymph-node dissection with the waterjet is technically feasible and safe in testis-cancer patient.
Corvin S, Sturm W, Schlatter E, Anastasiadis A, Kuczyk M, Stenzl A.
Department of Urology, Eberhard-Karls-University Tubingen, Germany.

Background and Purpose: The acceptance of open retroperitoneal lymph node dissection (RPLND) for stage I and II nonseminomatous testicular cancer has decreased because of the intraoperative and postoperative morbidity of the procedure. Laparoscopic RPLND is a minimally invasive and safe alternative for low-stage germ-cell tumors. It is, however, technically demanding and should therefore be performed only in experienced centers. The purpose of the present study was to evaluate the waterjet technique for laparoscopic RPLND. Patients and Methods: A series of 18 patients with clinical stage I testis cancer (group A) and 7 patients who had received chemotherapy for stage II disease (group B) underwent laparoscopic RPLND at our institution. The procedure was performed identically to the open approach using the modified template according to Weissbach and associates. The waterjet was used for removal of lymphatic tissue from the aorta and the vena cava, as well as from the sympathetic trunk. Results: The operation was completed in all patients without conversion to open surgery. The mean operating time was 232 +/- 48 minutes. The waterjet was able to remove lymphatic tissue easily and atraumatically. At pressures of 20 bar, the lymph-node capsule remained completely intact, thus avoiding tumor-cell spread. Antegrade ejaculation could be preserved in all patients, who, to date, show no evidence of disease. Conclusions: The waterjet allows the safe and complete removal of lymphatic tissue, leaving vulnerable anatomic structures intact. It can decrease the learning curve of laparoscopic RPLND and contribute to better acceptance of this procedure.

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Curr Treat Options Oncol. 2005 Sep;6(5):367-77.
Management of Patients with Low-stage Nonseminomatous Germ Cell Testicular Cancer.
Stephenson AJ, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. sheinfej@mskcc.org.

Management options for patients with clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT) include surveillance, retroperitoneal lymph node dissection (RPLND), or two cycles of bleomycin-etoposide-cisplatin (BEPx2) chemotherapy. The optimal management of these patients is controversial, as cure rates of 97% or greater are reported with each of these treatment modalities. Patients without evidence of lymphovascular invasion, a predominant component of embryonal carcinoma, or advanced pathologic (p) T stage (pT2 or greater) are at low risk for occult metastases and are optimal candidates for surveillance. Compliance with diagnostic testing and imaging is essential for a successful surveillance strategy to detect and treat metastases at an early stage. For patients who are not candidates for surveillance, RPLND offers several advantages over chemotherapy. RPLND alone is curative in 50% to 80% of CS I patients with pathologic stage (PS) II, and an estimated 75% of CS I patients avoid chemotherapy (as adjuvant therapy or for treatment of relapse). Virtually all patients are cured following two cycles of adjuvant chemotherapy for PS II disease, which is reserved for patients with high-volume (PN2-3) retroperitoneal disease. The poor outcome of patients with late retroperitoneal recurrence from unresected, chemorefractory germ cell testicular cancer indicates that RPLND is a vital component to the long-term cure of patients with NSGCT. Approximately 20% to 30% of patients with PS II disease have retroperitoneal teratoma (which is chemoresistant), and an estimated 5% of PS II patients have chemoresistant viable cancer following BEPx2 as primary therapy. When RPLND is omitted, these patients are at risk for late recurrence with potentially lethal consequences. Patients who relapse after RPLND are "chemotherapy-naive" and cured in virtually all cases with good-risk chemotherapy regimens. When nerve-sparing techniques are employed to preserve ejaculation, RPLND is also associated with a more favorable long-term toxicity profile compared with chemotherapy. In the absence of conclusive evidence from a randomized trial, we believe RPLND is the treatment of choice for patients with CS I NSGCT who are not candidates for surveillance, as it offers the greatest likelihood of long-term cure with considerably less morbidity than primary chemotherapy.

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J Endourol. 2005 Jul-Aug;19(6):683-92; discussion 692.
Laparoscopic retroperitoneal lymph-node dissection in the management of clinical stage I and II testicular cancer.
Albqami N, Janetschek G.
Department of Urology, Elisabethinen Hospital, Linz, Austria.

BACKGROUND AND PURPOSE: Laparoscopic retroperitoneal lymph-node dissection (RPLND) has been advocated for and utilized in the management of testicular cancer. In this overview, we present our technique and results in comparison with the worldwide experience with laparoscopic RPLND in the management of clinical stage I and II cancers. PATIENTS AND METHODS: Over the last 13 years, 162 patients with testicular cancer clinical stage I (N = 103) or II (N = 43 IIB, 16 IIC) underwent laparoscopic RPLND. All intraoperative and postoperative data were evaluated, as well as the worldwide experience with the procedure. With a mean follow-up of 62 months (range 6-113 months) for clinical stage I and 53 months (range 10-89 months) for clinical stage II, oncologic efficiency was evaluated. RESULTS: The procedure was feasible even after chemotherapy, with only three conversions to open RPLND in clinical stage I. The mean operative time was 217, 216, and 281 minutes for clinical stages I, IIB, and IIC, respectively. The mean blood loss was 144 mL and 165 mL for clinical stage I and II, respectively. The hospital stays were 3.6 and 3.8 days, respectively. During follow-up, we had two retroperitoneal relapses (1.2%) and four distant relapses (2.5%). CONCLUSION: Laparoscopic RPLND has demonstrated its surgical and oncologic efficacy. The morbidity and the complication rate are low. Recurrence rates are comparable to those of open surgery. Laparoscopic RPLND is safe, with less postoperative morbidity, quicker convalescence, better cosmetic results, and a diagnostic accuracy equal that of the open technique.

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Lancet. 2005 Jul 23-29;366(9482):293-300.
Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.
Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC TE19 collaborators and the EORTC 30982 collaborators.
Department of Medical Oncology, St Bart's and the London Hospital, London EC1A 7BE, UK. r.t.oliver@qmul.ac.uk

BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. INTERPRETATION: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.

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J Urol. 2005 Aug;174(2):557-60; discussion 560.
Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion.
Stephenson AJ, Bosl GJ, Bajorin DF, Stasi J, Motzer RJ, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers and Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

PURPOSE: The outcome after primary retroperitoneal lymph node dissection (RPLND) was analyzed in patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer with embryonal carcinoma predominance (ECP) or lymphovascular invasion (LVI). MATERIALS AND METHODS: Between 1989 and 2002, 267 patients with clinical stage I-IIA nonseminomatous germ cell testicular cancer, and ECP and/or LVI underwent RPLND. Patient information was obtained from a prospective database. Median followup was 53 months. RESULTS: Overall 42% of patients had pathological stage (PS) II disease, of whom 54% had low volume (PN1) disease and 16% had retroperitoneal teratoma. The 5-year progression-free probability was 90% overall, 90% for PS I and 86% for PN1. All patients with relapse were continuously free of disease following standard chemotherapy with or without resection of residual masses and the 10-year actuarial overall survival was 100%. When adjuvant chemotherapy was restricted to patients with PN2 disease, the estimated 5-year relapse rate was 9% and an estimated 72% of patients avoided chemotherapy. CONCLUSIONS: The low risk of systemic relapse in patients with PS I and PN1 after RPLND alone combined with the 16% incidence of retroperitoneal teratoma and the favorable morbidity profile supports RPLND over primary chemotherapy for the treatment of patients with low stage disease with ECP and/or LVI who are not candidates for surveillance. An estimated 72% of patients are spared the potential toxicity of chemotherapy if adjuvant therapy is restricted to patients with PN2. After primary RPLND and selective adjuvant chemotherapy late recurrence is distinctly uncommon and long-term cancer control is anticipated in essentially all patients.

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Urology. 2005 Jul 22; [Epub ahead of print]
Treatment of Testicular Cancer: Influence on Pituitary-Gonadal Axis and Sexual Function.
Lackner J, Schatzl G, Koller A, Mazal P, Waldhoer T, Marberger M, Kratzik C.
Department of Urology, Medical University of Vienna, Vienna, Austria.

OBJECTIVES: To investigate the influence of treatment for testicular cancer on the pituitary-gonadal axis and sexual function in long-time survivors after unilateral orchiectomy. METHODS: Blood was drawn from patients treated for testicular cancer during routine oncologic follow-up for measurement of luteinizing hormone, follicle-stimulating hormone, sexual hormone-binding globulin, testosterone, and bioavailable testosterone. Sexual function was evaluated using the International Index of Erectile Function 15-item (IIEF-15) questionnaire. Patients were grouped according to treatment: group 1 followed a surveillance strategy, group 2 received two cycles of carboplatin monotherapy, and group 3 underwent cisplatin, etoposide, and bleomycin chemotherapy. RESULTS: No statistically significant difference was found in the serum hormonal levels among the three groups, and all hormonal levels were within the 95% confidence range, except for follicle-stimulating hormone. The median serum testosterone level was 3.5 ng/mL in group 1, 3.9 ng/mL in group 2, and 4.2 ng/mL in group 3. In group 1, the median IIEF-15 score was 64.0, and the median Erectile Function (EF) domain score was 28. The median scores in groups 2 and 3 were 62.5 for IIEF-15 and 27.5 for EF and 65.0 for IIEF-15 and 30.0 for EF, respectively. No correlation was found between testosterone level and IIEF-15 or EF score. CONCLUSIONS: None of the treatments investigated had a significant influence on the serum hormonal levels in long-time survivors of testicular cancer. Patients undergoing chemotherapy have no greater risk of developing a hormonal disorder than those following a surveillance strategy, and therapy for testicular cancer is not a risk factor for erectile dysfunction.

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Urologe A. 2005 Jun;44(6):652-6.
[Lymphadenectomy for testicular cancer Diagnostic and prognostic significance as well as therapeutic benefit.]
[Article in German]
Krege S, Rubben H.
Urologische Klinik, Universitatsklinikum Essen, .

The rationale to perform retroperitoneal lymph node dissection (RPLND) in testicular cancer depends on the clinical stage and previous therapy. Thus, it can be performed either with diagnostic, prognostic, or therapeutic intention. In verified clinical stage I nonseminoma, RPLND provides one of three adjuvant options. To verify the clinical stage pathologically, surgery is done for diagnostic reasons, since CT scanning provides a false-negative staging in up to 30%. In higher stage lesions RPLND is a therapeutic procedure. The importance, however, of RPLND in clinical stage I nonseminoma is decreasing, since prognostic factors are available to stratify patients with either low or high risk for recurrence. Thus, these patients are selected for surveillance (low risk) or adjuvant chemotherapy (high risk).RPLND after chemotherapy is done for resection of residual tumor with a therapeutic intention. The histology of the residual mass is of prognostic importance and may help define further therapy. Resection of retroperitoneal metastases in patients with chemorefractory tumors is curative in about 25%.

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Cancer Treat Rev. 2005 May;31(3):197-209. Epub 2005 Mar 19.
Salvage, dose intense and high-dose chemotherapy for the treatment of poor prognosis or recurrent germ cell tumours.
El-Helw L, Coleman RE.
Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Whitham Road, Sheffield S10 2SJ, UK.

Most patients with metastatic testicular cancer are cured with cisplatin-based chemotherapy regimens. However, about 20-30% of patients with poor-risk germ cell tumours either fail to respond adequately or relapse after initial complete response. In an attempt to improve the treatment results, several phase II studies of high-dose chemotherapy (HDCT) and haematopoeitic stem cell support were performed initially in refractory or heavily pre-treated patients with germ cell tumours (GCT). Long-term disease-free survival (DFS) has been reported in nearly 13% (range 0-35%) of the patients in this group. Subsequently, HDCT trials have been conducted in first relapse; long-term DFS has been seen in 45% of the patients in these trials (range 21-67%). HDCT has also been evaluated in the first-line treatment of poor-risk GCTs; long-term DFS was achieved in 52% of the patients in this group (range 36-84%). Despite these encouraging results, a French randomised trial has failed to demonstrate any advantage of HDCT in the first-line treatment of poor-risk GCTs and thus the place of HDCT in routine practice remains uncertain. A number of randomised trials of HDCT are currently ongoing in the United States and Europe to better define the role of HDCT in this disease.

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Tumori. 2005 Mar-Apr;91(2):144-50.
Long-term results in patients affected by testicular seminoma treated with radiotherapy: risk of second malignancies.
Fatigante L, Ducci F, Campoccia S, Nocita AM, Paci E, Crocetti E, Cionini L.
Radiotherapy Division, Oncology Department, University of Pisa, Italy. lfatigante@tiscali.it

AIMS: To report clinical results in patients with testicular seminoma treated with postoperative radiotherapy with regard to survival, acute and late toxicity, and risk of second malignancy. MATERIALS AND METHODS: 176 stage I-Il testicular seminoma patients treated with radiotherapy from 1964 to 1994 at the Radiotherapy Division of Pisa University, using 60Co or Linac, were analyzed retrospectively. The follow-up ranged from 0.13 to 32.37 years, with a median of 12.1 years. The observed numbers of second malignancies were compared with those expected, taking into account age, sex, and incidence rates from the Tuscany Tumor Registry. RESULTS: Overall and specific survival at 10-15 years were 89-82% and 93-92%, respectively. Multivariate analysis revealed a significantly better survival in patients younger than 50 years and in those treated with Linac. Severe late sequelae occurred in 8% of the patients. Sixteen second malignancies were observed (14 solid tumors and 2 leukemias); median latency was 13 years (range, 3-27) and the observed/expected ratio 1.4 (P not significant). Solid cancers were localized in the bladder (2), kidney (2), skin (2), stomach (1), prostate (1), lung (1), larynx (1), uvea (1) and contralateral testicle (1); 1 patient presented an intestinal carcinoid and 1 a metastasis from an unknown primary. The risk of a second malignancy was higher in the patient group receiving less than 4000 cGy (observed/expected, 2.8; P = 0.015). CONCLUSIONS: The study confirmed the high cure rate in stage I-II seminomas after postoperative radiotherapy. Incidence of a second malignancy was higher than expected, but the difference was not statistically significant.

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Urol Oncol. 2005 Mar-Apr;23(2):141.
Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG)
Rowland RG. Classen J, Schmidberger H, Meisner C, Winkler C, Dunst J, Souchon R, Weissbach L, Budach V, Alberti W, Bamberg M, Department of Radiation Oncology, Universitatsklinikum, Tubingen, Germany.

A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2-97.4) and 99.6% (95% CI: 99.2-100%) at 5 years and 94.9% (95% CI: 92.5-97.4%) and 99.6% (95% CI: 99.2-100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any 'in-field' relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated.

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J Clin Oncol. 2005 Apr 1;23(10):2378-88.
Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy.
Thorsen L, Skovlund E, Stromme SB, Hornslien K, Dahl AA, Fossa SD.
Department of Psychosocial Oncology and Rehabilitation, The Norwegian Radium Hospital, N-0310 Oslo, Norway. lene.thorsen@radiumhospitalet.no

PURPOSE: To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness (CRF), mental distress, and health-related quality of life (HRQOL) parameters in young and middle-aged cancer patients shortly after curative chemotherapy. PATIENTS AND METHODS: One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast, gynecologic, or testicular cancer completed the trial. These patients were randomly allocated to either an intervention group (n = 59), which underwent a 14-week training program, or a control group (n = 52) that received standard care. Primary outcome was change in CRF, as determined by Astrand-Rhyming indirect bicycle ergometer test (maximum oxygen uptake [VO(2max)]), between baseline (T0) and follow-up (T1). Secondary outcomes were mental distress, as assessed by the Hospital Anxiety and Depression Scale, and HRQOL, as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire. Two-way analysis of covariance was used to analyze changes from T0 to T1. RESULTS: VO(2max) increased by 6.4 mL/kg(-1)/min(-1) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1) in patients in the control group (P < .01). The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group (P < .01). There were no intergroup differences in mental distress or HRQOL. CONCLUSION: A supervised, home-based, flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy, but it has no favorable effect on patients' experience of fatigue, mental distress, or HRQOL.

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Urologe A. 2005 Apr;44(4):352-7.
[Therapy for recurrent testicular cancer.]
[Article in German]
Kuczyk M, Horstmann M, Merseburger A, Beyer J.
Klinik fur Urologie, Eberhard-Karls-Universitat, Tubingen.

In the case of an insufficient response to primary treatment or a tumor relapse, regardless of an initially complete remission, conventional as well as high dose chemotherapy regimens are available as salvage therapy for metastatic germ cell tumors. A multimodal approach should include the radiation of simultaneously occurring brain metastases as well as the surgical resection of residual tumour masses still detectable after completion of chemotherapy. Nowadays, an attempt is made to adjust the salvage modality selected to the individual situation according to a risk stratification of patients. However, a recurrence-free survival of 50% is worse when compared with that observed after primary chemotherapy. Salvage therapy should be reserved for specialized centres due to the increased complexity of a salvage approach and a significantly increased therapy-induced morbidity.

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J Clin Oncol. 2005 Apr 20;23(12):2781-8.
Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome.
Stephenson AJ, Bosl GJ, Motzer RJ, Kattan MW, Stasi J, Bajorin DF, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.

PURPOSE: To investigate the impact of patient selection criteria on the outcome of patients with nonseminomatous germ cell testicular cancer (NSGCT) treated by primary retroperitoneal lymph node dissection (RPLND). Since 1999, our criteria have excluded patients with persistent postorchiectomy elevation of serum tumor markers (STM) or clinical stage (CS) IIB disease from RPLND. PATIENTS AND METHODS: Between 1989 and 2002, 453 patients underwent primary RPLND at our institution for CS I to IIB NSGCT. Patient information was obtained from a prospective database. Retroperitoneal pathology and relapse rates were compared for patients treated before and after application of the current selection criteria in 1999. RESULTS: By excluding patients with elevated STM or CS IIB disease after 1999, the proportion of pathologic stage II patients with low-volume (pN1) retroperitoneal disease increased significantly (40% before 1999 v 64% after 1999; P = .01), without significantly affecting the rate of retroperitoneal teratoma (21% v 22%, respectively; P = .89) or pathologic stage I disease (56% v 67%, respectively; P = .06). For patients who did not receive adjuvant chemotherapy, the 4-year progression-free probability improved significantly from 83% before 1999 (95% CI, 79% to 88%) to 96% after 1999 (95% CI, 91% to 100%; P = .005). Elevated postorchiectomy STM (P < .0001), clinical stage (P = .0002), and pre-1999 RPLND (P = .05) were independent pretreatment predictors of progression. CONCLUSION: Excluding patients with CS IIB disease or elevated postorchiectomy STM from primary RPLND has had a favorable impact on the extent of retroperitoneal disease and has significantly reduced the risk of relapse after RPLND. For patients with normal STM and CS I to IIA disease, the low rate of systemic progression and 22% incidence of retroperitoneal teratoma supports RPLND as the preferred primary intervention.

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Bull Cancer. 2005 Mar;92(3):267-71.
[Alternatives to the radiotherapy of stage I testicular seminoma]
[Article in French]
Paule B.
Service d'urologie, Hopital Henri-Mondor, 51, avenue du General-de-Lattre-de-Tassigny, 94100 Creteil.

Adjuvant irradiation is currently the most frequently used standard treatment for the clinical stage I seminoma (CSI) following orchiectomy. There is a potential carcinogenic risk with irradiation that prompted a search for alternative adjuvant treatment approach. The cure in CSI seminoma patients can be achieved with surveillance or chemotherapy. Surveillance takes into account the fact that 80% of patients do not need any adjuvant treatment after orchiectomy and are overtreated by adjuvant irradiation. Recently, one cycle of adjuvant carboplatin has been proven in a prospective randomized trial. Taken together, all three treatment options are acceptable standard strategies for the management of patients with CSI. Finally, the experience with surveillance strategy allowed an in-depth meta analysis of factors predictive for relapse discrimining the patients who are in need of post orchiectomy adjuvant treatment from those who safety can be followed by the surveillance strategy. However, this risk adapted approach is still under prospective evaluation.

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Int J Radiat Oncol Biol Phys. 2005 Mar 1;61(3):741-4.
Long-term results of para-aortic irradiation for patients with stage I seminoma of the testis.
Niazi TM, Souhami L, Sultanem K, Duclos M, Shenouda G, Freeman C.
Department of Oncology, Division of Radiation Oncology, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

PURPOSE: Adjuvant postoperative para-aortic lymph nodal irradiation is an acceptable alternative to para-aortic and ipsilateral pelvic irradiation postorchiectomy for patients with Stage I seminoma of the testis. In this article, we report the long-term results of our prospective evaluation of para-aortic irradiation only for such patients. METHODS AND MATERIALS: Between March 1991 and September 2000, 71 patients with Stage I seminoma were treated with adjuvant irradiation to the para-aortic region only after radical inguinal orchiectomy. Radiotherapy was delivered using parallel-opposed fields extending from T11 to L5. A total dose of 25 Gy in 15 fractions was prescribed to midpoint. Follow-up was performed every 3 months for the first year, every 4 months for the second and third years, every 6 months for the fourth and fifth years, and annually thereafter. Chest X-ray, tumor markers, and computed tomography scan of the pelvis were performed routinely as part of the follow-up investigation. RESULTS: At a median follow-up of 75 months, 68 of 71 patients are alive and free of relapse. Only 1 patient (1.4%) experienced failure in the ipsilateral inguinal nodal region. Two patients (2.8%) died of unrelated causes. The actuarial 10-year relapse free survival is 98.5% and the actuarial 10-year overall survival is 92%. No late toxicity has been encountered. CONCLUSION: Patients with Stage I seminoma of the testis may be safely treated with para-aortic radiotherapy only. Risk of pelvic failure is very low and treatment toxicity minimal.

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J Natl Cancer Inst Monogr. 2005;(34):12-7.
Spermatogenesis after cancer treatment: damage and recovery.
Howell SJ, Shalet SM.
Department of Endocrinology, Christie Hospital NHS Trust, Withington, Manchester, UK M20 4BX.

Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men, and alkylating agents are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas are rendered permanently infertile, whereas treatment with doxorubicin hydrochloride (Adriamycin), bleomycin, vinblastine, and dacarbazine appears to have a significant advantage, with a return to normal fertility in the vast majority of patients. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with a recovery of spermatogenesis in about 50% of the patients after 2 years and 80% after 5 years. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia following as little as 0.2 Gy. Testicular doses of less than 0.2 Gy had no significant effect on FSH levels or sperm counts, whereas doses between 0.2 and 0.7 Gy caused a transient dose-dependent increase in FSH and reduction in sperm concentration, with a return to normal values within 12-24 months. No radiation dose threshold has been defined above which permanent azoospermia is inevitable; however, doses of 1.2 Gy and above are likely to be associated with a reduced risk of recovery of spermatogenesis; the time to recovery, if it is to occur, is also likely to be dose dependent.

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Int J Radiat Oncol Biol Phys. 2005 Mar 1;61(3):736-40.
Long-term outcome of postorchiectomy surveillance for Stage I testicular seminoma.
Choo R, Thomas G, Woo T, Lee D, Kong B, Iscoe N, Danjoux C, Klotz L, Morton G, Chander S.
Division of Radiation Oncology, Toronto Sunnybrook Regional Cancer Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. richard.choo@sw.on.ca

PURPOSE: To examine the long-term outcome and patterns of relapse in clinical Stage I testicular seminoma managed with surveillance alone after radical inguinal orchiectomy. METHODS AND MATERIALS: This was a prospective, single-arm study. Patients with Stage I testicular seminoma were treated with surveillance alone in accordance with regular, predefined, schedules and investigations. RESULTS: The study accrued a total of 88 patients between 1985 and 1996. The median age at diagnosis was 34 years. The median tumor size was 3.5 cm. The median follow-up as of June 2003 was 12.1 years. Only 3 patients were lost to follow-up. Of the 88 patients, 71 remained free of relapse and 17 did not. The actuarial relapse-free rate was 83%, 80%, and 80% at 5, 10, and 15 years, respectively. Most relapses (15 of 17) were below the diaphragm. Of the 17 patients with relapse, 14 were treated with radiotherapy and 3 with combination chemotherapy. Only 1 had a second relapse and was further salvaged by chemotherapy. All 17 relapsed patients remained free of recurrence after salvage treatment. None died of seminoma. The statistically significant predictive factor for relapse on the Cox proportional hazards model was the presence of rete testis invasion (hazard ratio 3.5, p = 0.03). CONCLUSION: Surveillance with the reservation of radiotherapy or chemotherapy for salvage of relapse is a safe alternative to upfront postoperative adjuvant therapy for Stage I testicular seminoma.

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Expert Rev Anticancer Ther. 2005 Feb;5(1):123-38.
Recent advances in the treatment of testicular cancer.
Huddart RA, Birtle AJ.
The Royal Marsden NHS Foundation Trust & The Institute of Cancer Research, The Academic Unit of Radiotherapy & Oncology, Downs Road, Sutton, Surrey, SM2 5PT, UK. Robert.Huddart@icr.ac.uk

Testicular cancer is remarkable because it is curable by combination cytotoxic chemotherapy even when widely disseminated. Treatment is defined by widely accepted staging and prognostic factors. Three cycles of bleomycin, etoposide and cisplatin has been defined as the current optimum treatment in good prognosis metastatic disease, curing 90-95% of patients. Outcomes are less impressive for patients in intermediate and poor prognostic categories. A number of different approaches, including introduction of new agents and dose intensification, are being investigated to improve outcomes in these patients. Data developed over the last few years have identified increased risks of second malignancy and cardiovascular disease in long-term survivors. This has led to re-evaluation of strategies to manage Stage I patients. In particular, the use of radiotherapy in Stage I seminoma and the need for adjuvant therapy in Stage I nonseminoma are being re-examined. It is anticipated that advances in imaging and prognostic factors will facilitate this process.

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Expert Rev Anticancer Ther. 2005 Feb;5(1):109-12.
Therapy of testicular cancer: a surgeon's view.
Dindyal S, Bhuva N, Sooriakumaran P.
The Royal London Hospital, Holloway N7 6DD, UK. doctordindyal@hotmail.com

Treatment for metastatic testicular cancer has generally met greatest success when it has involved platinum-based chemotherapy and this is widely used for metastatic disease in most centers. However, surgical techniques should not be excluded. Retroperitoneal lymph node dissection has enabled a high cure rate to be achieved when used in conjunction with chemotherapy in patients with more advanced stage cancers.

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Crit Rev Oncol Hematol. 2005 Feb;53(2):141-64.
Germ cell tumours of the testis.
Gori S, Porrozzi S, Roila F, Gatta G, De Giorgi U, Marangolo M.
Ospedale Policlinico Monteluce, Perugia, Italy.

Cancer of the testis is a relatively rare disease, accounting for about 1% of all cancers in men. Cryptorchidism is the only confirmed risk factor for testicular germ cell tumour. The majority of GCT are clinically detectable at initial presentation. Any nodular, hard, or fixed area discovered in the testis, must be considered neoplastic until proved otherwise. The appropriate surgical procedure to make the diagnosis is a radical orchidectomy through an inguinal incision. Many GCT produce tumoural markers (AFP, HCG, LDH), who are useful in the diagnosis and staging of disease; to monitor the therapeutic response and to detect tumour recurrence. In 1997 a prognostic factor-based classification for the metastatic germ cell tumours was developed by the IGCCCG: good, intermediate and poor prognosis, with 5-year survival of 91, 79 and 48%, respectively. GCT of the testis is a highly table, often curable, cancer. Germ cell testicular cancers are divided into seminoma and non-seminoma types for treatment planning because seminomatous testicular cancers are more sensitive to radiotherapy. Seminoma (all stages combined) has a cure rate of greater than 90%. For patients with low-stage disease, the cure approaches 100%. For patients with non-seminoma tumours, the cure rate is >95% in stages I and II; it is approximately 70% with standard chemotherapy and resection of residual disease, if necessary, in stages III and IV. Minimum guidelines for clinical, biochemical, and radiological follow-up have been reported by ESMO in 2001.

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Gan To Kagaku Ryoho. 2005 Jan;32(1):33-8.
[The second-line chemotherapy for urological cancers]
[Article in Japanese]
Miki T, Mikami K, Mizutani Y.
Dept. of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

This review summarizes second-line chemotherapy for testicular cancer and urothelial cancer. For testicular cancer, the combination of bleomycin (BLM), etoposide (ETP), and cisplatin (CDDP) (BEP) is commonly used as an induction therapy. The combination of vinblastine (VLB), ifosfamide (IFM) and CDDP (VeIP) or ETP, IFM, and CDDP (VIP) is used for the second-line chemotherapy. When the efficacy of VeIP and VIP is not sufficient, high-dose chemotherapy or chemotherapy with new anticancer agents has been used for the second-line chemotherapy. High-dose chemotherapy showed long-term survival rates of 30-50%, but patients with testicular cancer resistance to CDDP have poor outcomes. Although new anticancer agents, such as paclitaxel (TXL), gemcitabine (GEM) and irinotecan have been introduced, further examinations are needed to evaluate these drugs. The combination of methotrexate, VLB, adriamycin, and CDDP (MVAC) is used as the standard chemotherapy for urothelial cancer. The outcomes of MVAC are favorable, but the duration of response is short and long-term survival cannot be expected. Recently, the efficacy of new anticancer agents including TXL and GEM against urothelial cancers has been demonstrated. Although TXL and GEM combination therapy as the second-line chemotherapy has some effects, more evidence needs to be accumulated to establish it as a second-line treatment.

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Eur Urol. 2005 Jan;47(1):64-71.
Repeat retroperitoneal lymphadenectomy in advanced testicular cancer.
Heidenreich A, Ohlmann C, Hegele A, Beyer J.
Division of Oncological Urology, Department of Urology, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany. axel.heidenreich@uk-koeln.de

OBJECTIVES: Repeat retroperitoneal lymph node dissection (RPLND) for the treatment of metastatic testicular cancer is an uncommonly performed procedure. We evaluated the location, pathohistological results, postoperative complications and therapeutic outcome in 17 patients being referred for repeat RPLND after failure of the primary retroperitoneal approach. PATIENTS AND METHODS: 18 patients underwent repeat RPLND after failed primary RPLND or residual tumour resection. We retrospectively analyzed preoperative patient characteristics, operative and pathohistological data from primary and repeat RPLND, morbidity and oncological outcome after surgery. RESULTS: All patients had nonseminomatous primaries with metastatic retroperitoneal lymph nodes; 4 and 14 patients had undergone primary RPLND and residual tumor resection (RTR), respectively, for metastatic testicular cancer. Prior to repeat RPLND all patients had undergone 4 cycles of salvage chemotherapy for locoregional recurrences only with negative tumour markers at time of surgery. All patients demonstrated residual masses requiring repeat RPLND. Retroperitoneal recurrences were located at multiple sites: retrocaval area with infiltration of the vena cava, interaortocaval and paraaortic region, retrocrural space, suprahilar region, outfield metastases in the iliac region. Two cases required resection of the vena cava due to infiltration, in one case an aortic graft and an iliac graft was necessary due to tumour infiltration of the adventitial layer of the vessels; nephrectomy and resection of the sigmoid was required in another 2 patients. The most significant complication was chylous ascites 1 and prolonged paralytic ileus in 1 patient. Pathohistological examination of the resected specimen revealed viable germ cell tumour elements in 4 patients (22.2%), necrosis/fibrosis in 8 patients (44.4%) and mature teratoma in 6 patients (33.3%). At a mean follow-up of 22 (1-45) months, the disease specific survival rate was 89% with significant differences between patients with necrosis (100%), mature teratoma (85%) and viable cancer (50%). CONCLUSION: Recurrences after RPLND usually reflect inadequate primary surgery especially in the retrocaval and suprahilar region. Repeat RPLND is safe and effective in the majority of patients; however, it requires careful preoperative planning with regard to potential involvement of adjacent vascular and visceral structures making close interdisciplinary collaboration necessary in many cases. Repeat RPLND is a mandatory surgery to be performed at centres of expertise.

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Urologe A. 2004 Dec;43(12):1500-6.
[Evidence-based indications for radiation therapy in testicular germ cell tumours]
[Article in German]
Souchon R, Classen J, Schmidberger H.
Klinik fur Strahlentherapie und Radioonkologie des Allgemeinen Krankenhauses Hagen gGmbH, Universitat Witten/Herdecke. souchon@akh-hagen.de

The intensity of adjuvant radiotherapy for stage I seminoma could be reduced substantially in recent years, achieving cure with low side effects and a low probability of late complications. Today a dose of 20 Gy is applied to the para-aortic lymphatics. Valuable treatment alternatives to radiotherapy have emerged: surveillance strategy allows 80% of patients to avoid further treatment. However, the remaining 20% will be exposed to potentially more intensive salvage therapy. Adjuvant carboplatinum chemotherapy offers similar disease-free survival to adjuvant radiotherapy. Long-term experience with late toxicity is not available. In seminoma CS IIA/B curative irradiation remains the standard treatment. Brain metastases of testicular germ cell tumors are treated with a combination of chemotherapy and cranial irradiation. In intratubular germ cell neoplasia (TIN), radiotherapy with 20 Gy will safely eliminate all TIN loci, but will destroy potential residual fertility.

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BJU Int. 2004 Nov;94(8):1196-201.
Testicular tumours (nonseminomatous).
Oosterhof GO, Verlind J.
Department of Urology, Academic Hospital Maastricht, the Netherlands. G.Oosterhof@urology.azm.nl

In view of the excellent results of multimodal therapy for nonseminoma testicular tumours, with chemotherapy and surgery, attempts have been made to reduce the side-effects of treatment in patients with a good prognosis, while maintaining efficacy. It is now generally accepted that surveillance after orchidectomy is suitable in patients with low-risk stage I disease. Nerve-sparing retroperitoneal lymph-node dissection as a primary treatment is a good alternative to primary chemotherapy in low-stage disease, i.e. high-risk stage I and stage IIa-b, enabling chemotherapy to be reduced by at least half, and decreasing the long-term side-effects of chemotherapy, especially cardiovascular, neuro-, nephro- and pulmonary toxicity. However, in patients with advanced disease and a poor prognosis, conventional chemotherapy is more likely to fail, and improving the treatment results by new schedules of chemotherapy (although more toxic) remains the main goal.

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Urologe A. 2004 Nov;43(11):1435-44; quiz 1445.
[Therapeutical options for seminomas at clinical stage I-IIA/B]
[Article in German]
Heidenreich A.
Sektion fur Urologische Onkologie, Klinik und Poliklinik fur Urologie, Universitat zu Koln. axel.heidenreich@uk-koeln.de

Seminomas represent the most common histological subgroup of all testicular germ cell tumors. About 75% of all seminomas present as clinical stage I disease at time of initial diagnosis and exhibit a long-term cure rate of 99%. Management strategies maintaining these high cure rates but minimizing the risks need are actively pursued. Currently, three treatment strategies are available for stage I seminomas: surveillance, radiotherapy and chemotherapy. Pathohistological prognostic factors allow an individualized risk-adapted therapeutic approach. Tumor size < or =4 cm and absence of rete testis invasion define a low-risk group with a recurrence rate of 12% being best managed by surveillance. Tumor size >4 cm and presence of rete testis invasion define a high-risk with a 35% risk of relapse, best managed by active therapy. Active treatment either consists of radiation of the ipsilateral paracaval or paraaortic lymph nodes with 20 Gy or of adjuvant chemotherapy with 2 cycles of carboplatin. It is currently unclear if 1 cycle carboplatin is as effective as 2 cycles; if this approach is performed follow-up has to be standardized and a compliance of both patient and physician are mandatory.

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Oncol Rep. 2004 Oct;12(4):867-70.
Health-related quality of life in patients with testicular cancer: a comparative analysis according to therapeutic modalities.
Miyake H, Muramaki M, Eto H, Kamidono S, Hara I.
Department of Urology, Hyogo Medical Center for Adults, Akashi 673-8558, Japan. hideakimiyake@hotmail.com

Investigating health-related quality of life (HRQoL) in testicular cancer patients has become important, because of an increasing number of young survivors with recent advance of multimodal therapy. The objective of this study was to compare the HRQoL in patients with advanced testicular cancer according to the types of treatment they received. Among 130 patients included in this study, 40 underwent surveillance monitoring (group A), 64 received cisplatin-based combination chemotherapy (group B), and 26 underwent infradiaphragmatic radiotherapy (group C). HRQoL in these 3 groups were evaluated using the SF-36 survey containing 36 questions that assess 8 aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. Furthermore, HRQoL in group B were analyzed according to the experience with retroperitoneal lymph node dissection (RPLND) or high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT). The follow-up period of the chemotherapy group was significantly shorter than that of the remaining 2 groups; however, scale scores were not affected by the duration of follow-up in these 3 groups. There were no significant differences in any scale scores among the 3 groups. In comparison with the general population in the USA, social functioning in the 3 groups with testicular cancer was significantly lower, whereas vitality in these groups was significantly higher. Furthermore, in group B, there were no significant differences in any scale scores between patients with and without RPLND, while patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy following standard-dose chemotherapy despite the absence of a significant difference in the remaining 7 scores irrespective of the experience with high-dose chemotherapy. These findings suggest that 7 of the 8 scale scores of HRQoL examined by the SF-36 survey were satisfactory in patients with testicular cancer regardless of the 3 treatment modalities, and that there were no significant differences in any scale scores among these groups. Moreover, the HRQoL was not affected by experience with RPLND or high-dose chemotherapy except for mental health in patients undergoing high-dose chemotherapy. Therefore, the overall HRQoL in patients with testicular cancer may be generally favorable and not affected by differences in treatment type.

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J R Soc Health. 2004 Sep;124(5):217-8.
Testicular cancer.
Shabbir M, Morgan RJ.
Department of Surgery, Royal Free and University College Medical School, Royal Free Hospital Campus, London NW3 2QG, England.

Testicular cancer is a rare condition, accounting for approximately 1-1.5% of all cancers in men. It is the most common cancer affecting men in their 20s and 30s. Little is known about the exact cause of this disease, although numerous risk factors have been recognised. Treatment of testicular cancer has been extremely successful, with impressive cure rates reported. This is due to the excellent tumour response to chemotherapy and radiotherapy, and also to the diagnosis and follow-up regimes.

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J Clin Oncol. 2004 Sep 1;22(17):3563-9.
Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study—Pediatric Oncology Group 9048 and Children's Cancer Group 8891.
Rogers PC, Olson TA, Cullen JW, Billmire DF, Marina N, Rescorla F, Davis MM, London WB, Lauer SJ, Giller RH, Cushing B; Pediatric Oncology Group 9048; Children's Cancer Group 8891.
British Columbia Children's Hospital, Vancouver, Canada.

PURPOSE: To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity. PATIENTS AND METHODS: Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5. Patients received four cycles of therapy at 21-day intervals. RESULTS: Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled. Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16). Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%. EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively. Two patients died from recurrent disease, and one patient died of secondary acute myelocytic leukemia. Infrequent grade 3 to 4 hematologic toxicity was reported. No grade 3 to 4 renal, pulmonary, or ototoxicity was observed. CONCLUSION: Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.

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Clin J Oncol Nurs. 2004 Aug;8(4):355-60.
Surgical management of testicular cancer.
Stevenson TD, McNeill JA.
Penn State Cancer Institute, Mount Nittany Medical Center, State College, PA, USA. psurat92@aol.com

Surgery is an integral component in the management of testicular cancer. Prior to the advent of cisplatin chemotherapy, a retroperitoneal lymph node dissection (RPLND) was the only chance for cure of testicular cancer. Over the years, the surgical techniques have been improved greatly to decrease the occurrence of complications (e.g., incidence of retrograde ejaculation). Currently, RPLND can be done as the initial therapy or after chemotherapy. In either situation, the postoperative management of patients with testicular cancer can be complicated and requires thorough, ongoing assessment. This article presents the surgical indications for RPLND and the nursing management.

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Urol Clin North Am. 2004 Aug;31(3):619-27, xi.
Pediatric urologic oncology: bladder, prostate, testis.
Wu HY, Snyder HM 3rd.
University of Pittsburgh and Department of Urology, Children's Hospital of Pittsburgh, 4A-424 Desoto Wing, 3705 5th Avenue, Pittsburgh, PA 15213, USA. wuhy@chp.edu

Although treatment for bladder, prostate, and testis cancer comprises a large part of adult urologic practice, the tumors that affect these organs in children are rare. Rhabdomyosarcoma,which affects the bladder, prostate, vaginal, and paratesticular areas,is treated with a combination of surgery, chemotherapy, and radiation. Most transitional cell carcinomas of the bladder and prepubertal testis tumors are managed surgically owing to the low stage at presentation. Application of the technical advances learned in adults with tumors of the bladder, prostate, and testis, combined with an understanding of the difference in tumor biology, helps urologists improve the treatment of these tumors in children.

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Urol Oncol. 2004 May-Jun;22(3):225-33; discussion 234-5.
The role of retroperitoneal lymph node dissection in the management of testicular cancer.
Stephenson AJ, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Despite continued refinement in terms of technique and the integration of retroperitoneal lymph node dissection (RPLND) in the management of patients with testicular cancer, RPLND remains an essential component in the ultimate cure of these patients. The failure to eradicate all disease in the retroperitoneum exposes patients to the risk of late relapse events with potentially lethal consequences. For patients with low-stage nonseminomatous germ cell tumor (NSGCT), primary RPLND is an important staging tool to define subsequent treatment requirements, simplify the follow-up of patients by obviating the need for routine abdominal imaging, and limit the exposure of patients to the long-term toxicity of chemotherapy. RPLND alone is curative in up to 90% of patients with low-volume retroperitoneal disease. In the post-chemotherapy setting, the inability to reliably exclude the presence of teratoma or viable germ cell cancer in the retroperitoneum mandates that post-chemotherapy RPLND be performed for all NSGCT patients with residual masses. With improvements in surgical technique and perioperative care, RPLND is associated with minimal short- and long-term morbidity in the hands of experienced surgeons at dedicated centers. This article reviews the role of RPLND in the management of patients with NSGCT at all stages and its role in advanced seminoma. Copyright 2004 Elsevier Inc.

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Ann R Coll Surg Engl. 2004 Jul;86(4):289-91.
Is high cord radical orchidectomy always necessary for testicular cancer?
Ashdown DA, Bodiwala D, Liu S.
Department of Urology, City General Hospital, Stoke on Trent, Staffordshire, UK.

BACKGROUND: Radical high cord inguinal orchidectomy remains the standard for diagnosis, staging and treatment of testicular neoplasms. Low cord orchidectomy is an alternative to the high cord orchidectomy. OBJECTIVE: To test the hypothesis that there is no difference in relapse rate or mortality between high and low cord orchidectomy for the treatment of testicular cancer. METHODS: A retrospective study was undertaken of all orchidectomies performed for testicular cancer at our hospital between 1981 and 2002. RESULTS: Overall, 120 high cord orchidectomies and 102 low cord orchidectomies were performed for testicular cancer between 1981 and 2002 at our hospital. Analysis showed that there was no significant difference in the mean age of the patients, the rate of relapse, mean time to relapse or survival between surgical approach for stage 1 tumours. For stage 2-4 tumours, there were not sufficient numbers to comment on the statistical significance of relapse or survival differences. CONCLUSIONS: The trend suggests that there is no statistically significant difference in the rate of relapse and mortality between high and low cord orchidectomy for clinically stage 1 tumours. We would, therefore, advocate either a high or low cord orchidectomy for clinically stage 1 tumours.

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Nurs Clin North Am. 2004 Jun;39(2):327-40.
Cancers of the prostate, penis, and testicles: epidemiology, prevention, and treatment.
Stotts RC.
The University of Tennessee Health Science Center, College of Nursing, 877 Madison Avenue, Room 612, Memphis, TN 38163, USA. cstotts@utmem.edu

Cancer is a disease that most people fear. Nurses are required to provide information on how to avoid cancer, and, once the diagnosis is made, how to cope with it. Prevention and early detection of the cancers described in this article are in the very early stages of knowledge development, but general health promotion guidance can be offered on how to avoid most cancers (ie, no tobacco use, a high-fiber and low fat diet, exercise, and maintaining a normal weight). Nurses also can advise patients to be screened for colorectal cancer at the appropriate ages and time intervals and to be aware as new developments occur in the scientific base for screenings in the areas of prostate, penile, and testicular cancer. Finally, coping with these forms of cancer often requires the patient to make major lifestyle and psychological changes, especially if surgery in the genital area occurs. Decreased libido, incontinence, and impotence are major complications that can occur with these illnesses. The male cancers described vary tremendously in their prevalence, incidence, mortality, treatment, and survival rates. Within this group, there are remarkably positive outcomes and outcomes much in need of improvement. Penile and testicular cancers are the bright spots in this picture; both are uncommon, and both are eminently treatable. Prostate cancer, on the other hand, is quite common, difficult to screen, difficult to treat without major sexual problems, and yet receives relatively little funding from the NIH. Although as many men die from prostate cancer as women die from breast cancer, NIH funds breast cancer research at much higher levels than prostate cancer. According to the latest data available at the NIH Web site, during the 1990s, the amount of NIH funding varied from four times more for breast cancer (1993) to 2.9 times more in 1999. For fiscal year 2002, NIH is providing $522 million in funding for breast cancer and $278 million for prostate cancer. Private foundation funds for prostate cancer are much smaller than those available for breast cancer. Both types of cancer are extremely important to address, and both should receive adequate research attention. Nurses can advocate for more funding for prostate cancer, from basic science approaches to behavioral science strategies.

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Eur Urol. 2004 Jun;45(6):754-59; discussion 759-60.
Stage II testicular seminoma: patterns of recurrence and outcome of treatment.
Chung PW, Gospodarowicz MK, Panzarella T, Jewett MA, Sturgeon JF, Tew-George B, Bayley AJ, Catton CN, Milosevic MF, Moore M, Warde PR.
Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.

OBJECTIVES: To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse. METHODS: From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse. RESULTS: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. CONCLUSIONS: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.

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Curr Opin Oncol. 2004 May;16(3):253-6.
Testicular cancer.
MacVicar GR, Pienta KJ.
University of Michigan Medical Center, Ann Arbor, Michigan, USA.

PURPOSE OF REVIEW: The purpose of this article is to review the recent clinically relevant literature on testicular cancer. RECENT FINDINGS: Recent studies suggest that an increased incidence of testicular cancer is due to a birth-cohort effect and secondary to early exposure. Work on identifying tumor prognostic characteristics suggests that proliferation and apoptosis markers as well as serum lactate dehydrogenase isoenzyme 1 (S-LD-1) may have value. Poor-risk patients may benefit from intensive treatment despite a possible increased risk of significant toxicity and treatment related deaths. Studies continue to show the efficacy of radiation for stage I and stage II seminoma, but another study adds to the evidence that adjuvant carboplatin may be an acceptable alternative in stage I disease. Surgical studies suggest that even patients with minimal findings on computed tomography after chemotherapy are at risk for harboring vital tumor. Surveillance is shown to be an acceptable choice for highly compliant patients with early stage disease. Risk factors predictive of bleomycin pulmonary toxicity are proposed. Fertility remains an area of concern. SUMMARY: Testicular cancer research continues to modify current therapies, increase the understanding of the molecular basis of the disease, and improve the risk stratification of the patient population so as to minimize exposure to treatment-related morbidity and toxicity.

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J Urol. 2004 May;171(5):1839-41.
Complications of post-chemotherapy retroperitoneal lymph node dissection for testis cancer.
Mosharafa AA, Foster RS, Koch MO, Bihrle R, Donohue JP.
Department of Urology, Indiana University, Indianapolis, USA.

PURPOSE: Post-chemotherapy retroperitoneal lymph node dissection (PC RPLND) is a tool in the management of testis cancer. Our impression has been that the short-term morbidity of standard PC RPLND has diminished with time. Therefore, we attempted to verify this hypothesis by evaluating the morbidity of the procedure in 2 comparable groups of patients from 2 different periods. MATERIALS AND METHODS: We compared 150 patients who underwent post-chemotherapy RPLND between July 2000 and July 2002 to 79 patients who underwent the same procedure between 1990 to 1992. All patients had clinical stage II-III testis cancer and had received 3 to 4 courses of standard platinum based chemotherapy before surgery. We compared surgical morbidity and postoperative complications in both groups. We also assessed a number of factors (patient characteristics, mass size, pathological features and surgical aspects) that could impact the rate of complications. RESULTS: The 2 groups were comparable regarding preoperative clinical stage, patient characteristics and postoperative pathological findings. PC RPLND procedures were performed using the same technique. Compared to patients in the 1990 to 1992 group, the patients from the 2000 to 2002 group had fewer intraoperative complications and additional procedures (44 [29.3%] of 150 versus 41 [51.9%] of 79, p = 0.0008), a trend toward a lower postoperative complication rate (10 [6.7%] compared to 11 [13.9%], p = 0.07) and shorter hospital stay (average 5.6 versus 8.4 days [p <0.0001]). CONCLUSIONS: With time morbidity and hospital stay after standard PC RPLND have decreased. This finding probably reflects differences in patterns of care rather than changes in surgical technique. Therefore, comparing newer surgical techniques to historical controls is inappropriate since differences may not actually represent the technical advances of the newer procedure.

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World J Urol. 2004 Apr;22(1):47-54. Epub 2004 Apr 03.
Late relapse of testicular cancer.
Lipphardt ME, Albers P.
Department of Urology, Bonn University, Bonn, Germany.

Due to its unique biological behavior, late relapse (LR) of testicular cancer has recently been described as an own tumor entity. It is currently defined as tumor recurrence more than 2 years after complete remission following primary treatment including chemotherapy. The incidence ranges from 2 to 6%, with a median relapse-free interval of 5.4-7.1 years from the initial treatment. Although histology shows a germ cell tumor (GCT) origin, the clinical biology is different. The dominant characteristics are slow tumor growth and chemoresistance. Molecular analysis currently focuses on the mechanisms of drug resistance. The initial response to chemotherapy is less than 30% and in most cases complete surgical resection remains the only treatment option with favorable long-term results. The most common site of LR is the retroperitoneum, with undifferentiated cancer (yolk sac) being the most frequent histology. In most cases, patients have already undergone previous retroperitoneal surgery. The overall cure rate is only about 50%, hence, adequate treatment of the primary tumor is essential to prevent the development of LR.

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Eur Urol. 2004 Apr;45(4):495-8.
Spermatocytic seminoma: a review.
Chung PW, Bayley AJ, Sweet J, Jewett MA, Tew-George B, Gospodarowicz MK, Warde PR.
Department of Radiation Oncology, Princess Margaret Hospital, 610, University of Toronto, Toronto, Ontario, Canada M5G 2M9.

OBJECTIVE: Spermatocytic seminoma is a rare testicular tumour that has an extremely low rate of metastasis. We present a review of the management of this malignancy at our institution. METHOD AND MATERIALS: Between 1981 and 1999, 771 patients were treated at our institution for testicular seminoma. Of these, 13 had spermatocytic seminoma; one was excluded as he had treatment elsewhere. All patients were initially diagnosed at other hospitals and subsequently referred for management and had their pathology reviewed locally prior to any treatment. RESULTS: All patients had stage I disease, 5 patients received radiotherapy to the para-aortic and pelvic nodes, the other 7 were followed on a surveillance program. The median age was 62 years. With a median follow-up of 8.5 years no relapses were observed. Some patients exhibited adverse histological features associated with increased risk of relapse in seminoma including rete testis invasion and large primary tumour size. CONCLUSIONS: Spermatocytic seminoma may occur in younger patients and may not be restricted to the older population as commonly reported. Surveillance following orchidectomy is the preferred management option.

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Br J Cancer. 2004 Mar 22;90(6):1169-75.
Paclitaxel-containing high-dose chemotherapy for relapsed or refractory testicular germ cell tumours.
McNeish IA, Kanfer EJ, Haynes R, Giles C, Harland SJ, Driver D, Rustin GJ, Newlands ES, Seckl MJ.
Department of Medical Oncology, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK.

High-dose regimes containing etoposide, carboplatin and an oxazaphospharine can salvage 30-40% of patients with relapsed or refractory male germ cell tumours (GCTs). The additional benefit of paclitaxel in such high-dose therapy has not been tested. Between March 1995 and November 2002, 36 male GCT patients were treated with Carbop-EC-T (paclitaxel 75 mg x m(-2), etoposide 450 mg x m(-2), carboplatin AUC 10 on days -7, -5 and -3 and cyclophosphamide 60 mg x kg(-1) on days -5 and -3) followed by peripheral blood stem cell infusion (day 0). The 1-year overall survival rate for all patients is 67% (median follow-up 29 months). For the 24 patients with cisplatin-sensitive disease, the 1-year overall and event-free survivals are 88 and 64%, respectively. For those with cisplatin refractory or absolutely refractory disease, the 1-year overall survival is 25%. In all, 12 patients relapsed at a median duration of 5 months, 11 of whom have died. There were also six treatment-related deaths, five associated with pneumonitis. Pulmonary toxicity has been reported with paclitaxel in other high-dose regimes. Since altering our protocol so that paclitaxel is infused over 24 h with steroid prophylaxis, only one of 18 patients (13 testicular GCTs and five other tumour types) has had a treatment-related death. Our results suggest that Carbop-EC-T may enable a greater proportion of patients with relapsed and refractory GCTs to enter long-term remission.

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Acta Oncol. 2004;43(2):134-41.
Long-term sequelae after cancer therapy--survivorship after treatment for testicular cancer.
Fossa SD.
Norwegian Radium Hospital, Department of Clinical Cancer Research, Montebello, Oslo, Norway. s.d.fossa@klinmed.uio.no

This paper is based on a lecture given during the Oncological Forum, Oslo, in November 2002. Long-term morbidity in cancer survivors is exemplified by results of clinical research in testicular cancer survivors (TCSs). The most serious complication is the development of second, non-germ cell malignancies (relative risk [RR]: 1.4-1.6). After infradiaphragmatic radiotherapy, most solid malignancies are diagnosed within or near the target volume. Combined chemo-radiotherapy increases this risk. Chemotherapy-induced leukaemia is usually reported after 4-7 years. After 3 or 4 cycles of cisplatin-based chemotherapy, 15-20% of TCSs suffer from peripheral sensory neuropathy, Raynaud-like phenomena and/or ototoxicity. Hypogonadism is observed in 16%. The risk of cardiac complications is increased by hypercholestorolaemia and abnormal body mass. Pelvic radiotherapy and cisplatin-based chemotherapy are followed by transient oligo/azospermia with recovery after 6-12 months. The risk of surgery-related 'dry ejaculation' is significantly reduced after unilateral and nerve-sparing retroperitoneal lymph node dissection, but infertility remains a long-term problem in 10-15% of survivors. Most TCSs describe their quality of life as comparable with that of the age-matched male general population. Not all long-term complications are avoidable after curative treatment of cancer. Knowledge of post-treatment long-term morbidity is essential for early recognition and treatment of late complications, and enables adequate counselling of new cancer patients.

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Clin Oncol (R Coll Radiol). 2004 Feb;16(1):40-7.
The management and survival of patients with advanced germ-cell tumours: improving outcome in intermediate and poor prognosis patients.
Bhala N, Coleman JM, Radstone CR, Horsman JM, George J, Hancock BW, Hatton MQ, Coleman RE.
Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield, UK.

AIMS: The survival of germ-cell tumours (GCT) was transformed after the introduction of cisplatin-based therapy. Previous trials have indicated BEP (bleomycin, etoposide and cisplatin) as the optimum treatment, although some centres including our own advocate the use of the alternating regimen POMB-ACE (cisplatin, vincristine, methotrexate, bleomycin and dactinomycin, cyclophosphamide and etoposide) for men with intermediate or poor prognosis disease. We analysed the survival and management of GCT patients treated at a specialist cancer centre in relation to internationally recognised prognostic groupings. MATERIALS AND METHODS: We retrieved patient information using the Trent Testicular Tumour Registry and supplemented it with information from patient notes. This included all patients with Royal Marsden Hospital Stage II, III and IV disease and patients with stage I disease at diagnosis with raised markers or subsequent relapse. We compared the efficacy and toxicity of the BEP and POMB-ACE chemotherapy regimens, and assessed relapse-free and overall survival. RESULTS: We identified 178 non-seminomatous germ cell tumours (NSGCT) and 71 seminoma patients. Overall survival was similar to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification for the good (95% vs 92%) and intermediate groups (82% vs 80%). The outcome for the poor prognosis group was better than expected in our series (57% vs 48%). There was a higher proportion of both immediate and late side-effects with POMB-ACE. CONCLUSION: Survival and disease progression rates at this single institution were at least as good as reported by the IGCCCG and somewhat better for the poor-prognosis group. This may reflect use of the POMB-ACE chemotherapy regimen as opposed to standard BEP regimen. However, a randomised comparison of BEP and POMB-ACE would be required to validate this.

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Cancer Radiother. 2003 Nov;7 Suppl 1:70s-77s.
[Radiotherapy of testicular seminoma: changes over the past 10 years]
[Article in French]
Mirimanoff RO.
Centre hospitalier universitaire de Vaudois (CHUV), 46, rue du Bugnon, CH-1011 Lausanne, Suisse. Rene-Olivier.Mirimanoff@chuv.hospvd.ch

Radiotherapy is generally considered as the standard treatment for most testicular seminomas. However, there have been substantial changes in the management of these tumours over the past few years. In early seminoma, there is a trend towards a decrease in treatment intensity or even towards therapeutic abstention (i.e. surveillance); whereas in advanced cases, combination chemotherapy is taking over from radiotherapy. In stage I, where cure rates are almost 100%, the limiting of the lymph node area to be irradiated and decrease of the dose to 20-25 Gy was followed by very low long-term toxicity rates, and a very small risk of infertility, without compromising the overall prognosis. Surveillance is an acceptable alternative to postoperative radiotherapy. However, the risk of nodal relapse is around 18-20%. With surveillance, the frequency and duration of follow-up is increased in comparison to the same with postoperative radiotherapy, with higher cost. In stage IIa, radiotherapy remains the standard but recent studies have shown that limiting the nodal volume to the paraortic area is justified as in stage I. In stage IIb and higher, combination chemotherapy is almost always given. However, the association between carboplatin and radiotherapy represents an efficient and well-tolerated alternative. Late tissue damage and the risk of decrease in fertility are minimized with novel radiotherapeutic approaches. However, the occurrence of second cancers in the long term is a matter of concern. It is possible though, that patients with seminoma have a tendency per se to develop second cancers. The prognosis of cryptorchid seminoma and of HCG-producing seminoma has been the subject of controversy but recent large studies have demonstrated that stage for stage, the cure rates are similar to those of other seminomas.

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Cancer Radiother. 2003 Nov;7 Suppl 1:60s-69s.
[Cancer of the testis: role of radiotherapy in 2003]
[Article in French]
Clippe S, Flechon A, Droz JP.
Departement de radiotherapie, centre Leon-Berard, 28, rue Laennec, 69008 Lyon, France.

Germ-cell tumors of the testis are rare tumors of the young adult. Half of them are seminoma. The majority of patients have disease limited to the testis. Radiotherapy still remains the standard treatment of these patients. Almost all patients are cured by orchidectomy and radiotherapy on the lomboaortic area extended to homolateral iliac area. The dose is 24 to 30 Gy in a standard fractionation. Different studies are ongoing to reduce the irradiation field (omission of the pelvic irradiation), to decrease irradiation dose (to 20 Gy). Other treatment options are strict surveillance and adjuvant carboplatin based chemotherapy. None of these options are standard treatments. A strict attention must be directed on controlateral germ-cell tumors and second cancers.

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J Clin Oncol. 2004 Feb 15;22(4):640-7. Epub 2004 Jan 15.
Mortality after cure of testicular seminoma.
Zagars GK, Ballo MT, Lee AK, Strom SS.
Department of Radiation Oncology, Box 97, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. gzagars@mdanderson.org

PURPOSE: To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). PATIENTS AND METHODS: From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. RESULTS: After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P <.01). An increased mortality was evident in patients treated with and without mediastinal XRT. CONCLUSION: Long-term survivors of seminoma treated with post-orchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

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J Urol. 2004 Jan;171(1):161-3.
Experience with testis sparing surgery for testicular teratoma.
Shukla AR, Woodard C, Carr MC, Huff DS, Canning DA, Zderic SA, Kolon TF, Snyder HM 3rd.
Division of Pediatric Urology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.

PURPOSE: Testicular teratoma is a rare neoplasm affecting the pediatric population and has classically been reported to be the second most common testis tumor in children behind yolk sac tumors. Testicular teratomas are benign and partial orchiectomy may be considered. We describe our single institution experience with testicular teratoma and definitive treatment with testis preserving surgery. MATERIALS AND METHODS: We reviewed the pathology records at our institution for all testicular and paratesticular tumors diagnosed between 1976 and November 2002 in males younger than 18 years. We specifically examined the prepubertal incidence of teratoma, including epidermoid cysts, and our experience with testis preserving surgery. Preoperative and postoperative ultrasonography images were used to calculate the atrophy index following surgery. Patients were contacted for long-term followup. RESULTS: Of 77 primary testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean patient age at treatment was 34.4 months (range 4 months to 10 years). All boys presented with a painless scrotal mass, cystic foci within an intratesticular mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean 7-year followup no patient has presented with recurrent tumor in the ipsilateral or contralateral testicle. Postoperative physical examination and scrotal ultrasound were obtained in 9 patients at a median followup of 10.2 months, and there was no evidence of testicular atrophy or persistent discomfort. CONCLUSIONS: Unlike previously published series based on tumor registries, benign teratoma was the most common pediatric testicular tumor treated at our institution. Our single institution experience with testis preservation and long-term followup confirms the role and safety of this technique. Testis sparing surgery remains our technique of choice for testicular teratoma.

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Urology. 2003 Aug;62(2):324-7.
Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer: a long-term update.
Bhayani SB, Ong A, Oh WK, Kantoff PW, Kavoussi LR.
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

OBJECTIVES: To assess retrospectively the long-term cancer control in patients undergoing laparoscopic retroperitoneal lymph node dissection (RPLND) in the management of clinical Stage I nonseminomatous germ cell testicular tumors. METHODS: A retrospective review of 29 patients undergoing laparoscopic RPLND was performed. All patients had clinical Stage I nonseminomatous germ cell testicular tumor, with vascular invasion and/or embryonal carcinoma in the orchiectomy specimen. A modified template dissection was performed. Patients with retroperitoneal metastases were offered two cycles of chemotherapy. A modified follow-up schedule was used in patients with pathologically negative nodes. RESULTS: Lymph nodes were negative in 17 of 29 patients. Of these 17 patients, 15 had no recurrence and were free of disease with 5.8 years of follow-up. Two patients had recurrence, one in the chest, and one biochemically, and both were free of disease after chemotherapy. Twelve of 29 patients had lymph nodes with metastatic testicular cancer. Ten of these patients underwent adjuvant chemotherapy and were free of disease with 6.3 years of follow-up. One patient had a biochemical recurrence after positive RPLND and was salvaged with chemotherapy. One patient was observed after positive RPLND and was free of disease with 4.9 years of follow-up. The only long-term complication was retrograde ejaculation in 1 patient. CONCLUSIONS: Laparoscopic RPLND is a safe, minimally invasive treatment option in patients with clinical Stage I nonseminomatous germ cell testicular tumor. The cancer control appears to be similar, with minimal morbidity compared with the open procedure.

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BJU Int. 2003 Jul;92(1):47-52; discussion 52.
Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only.
Santoni R, Barbera F, Bertoni F, De Stefani A, Livi L, Paiar F, Scoccianti S, Magrini SM.
Radiation Oncology Departments, University of Firenze, Firenze, University of Rome, Tor Vergata, Roma, Italy. riccardo.santoni@uniroma2.it

OBJECTIVE: To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970-1999. PATIENTS AND METHODS: In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS: The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the 'dog leg' field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true 'in-field' recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION: Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the 'dog-leg' group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.

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BJU Int. 2003 Jul;92(1):36-42.
Improved prognosis of patients with intermediate- and poor-risk nonseminomatous germ cell tumours by optimizing combined treatment.
Pentheroudakis G, De Bono JS, Kaye SB, Simpson A, Paul J, Brown I, Pamenter B, Kirk A, Vasey P, Raby N, Kirk D.
CRC Department of Medical Oncology, Western Infirmary, Glasgow, Scotland, UK. avassou@otenet.gr

OBJECTIVE: To assess whether the optimal use of combined treatment with chemotherapy and appropriately timed surgical intervention by a specialized team might improve the outcome for patients with poor- and intermediate-prognosis (International Germ Cell Consensus Classification, IGCCC) nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: Between 1984 and 1998, 47 patients with intermediate (16) and poor prognosis (31) NSGCT were treated; 43 had a testicular and four a retroperitoneal primary. RESULTS: Of the 47 patients only seven (15%) had a complete radiological response after primary chemotherapy; 36 (77%) required surgery after chemotherapy (29 para-aortic lymphadenectomy, 13 resection of pulmonary metastases, two each excision of supraclavicular and retrocrural lymph nodes and one resection of brain metastases; 13 required surgery at more than one site). There was no surgical mortality, with postoperative wound pain the commonest morbidity. On pathology, the resected masses were mature teratoma in 13, necrosis in 12 and malignant disease in 11 patients, the resection being complete in 30. There were microscopically positive margins in the other six patients, all but one having viable residual cancer. Of the 47 patients, 18 needed treatment for relapse, with four having surgery for growing mature teratoma, six chemotherapy plus surgery and eight salvage chemotherapy alone. Of 31 patients, 22 (71%) with a poor and 13 of 16 with an intermediate prognosis were alive at a median (range) follow-up of 94 (41-171) months; of all 47, 34 (72%) remain in complete remission. Ten patients died from disease progression. The presence of residual malignant disease at the resection margin was significantly associated with poorer survival (hazard ratio 7.21, P = 0.0016). Prognostic factors, e.g. number of involved sites, IGCCC group and viable tumour in resected masses, were not significant. The 5-year overall and relapse-free survival (95% confidence interval) was 81 (69-93)% and 57 (43-71)%, respectively. CONCLUSION: The optimal delivery and timing of chemotherapy and surgical resection by a specialist team of oncologists, urological and cardiothoracic surgeons is critical in treating poor-risk NSGCT and might be responsible for improving the outcome of these patients. The detection of residual malignant disease after chemotherapy by positron emission tomography should be investigated to identify those who might benefit from further systemic treatment before complete surgical resection.

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Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):746-8.
Appropriate radiation volume for stage IIA/B testicular seminoma.
Chung PW, Warde PR, Panzarella T, Bayley AJ, Catton CN, Milosevic MF, Jewett MA, Sturgeon JF, Moore M, Gospodarowicz MK.
Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.

PURPOSE: Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. METHODS AND MATERIALS: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (+/- contralateral) pelvic lymph nodes (dose: 25-35 Gy). RESULTS: With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. CONCLUSIONS: Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only.

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J Urol. 2003 Jun;169(6):2126-8.
Is post-chemotherapy resection of seminomatous elements associated with higher acute morbidity?
Mosharafa AA, Foster RS, Leibovich BC, Bihrle R, Johnson C, Donohue JP.
Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

PURPOSE: A seminomatous element in patients undergoing retroperitoneal lymph node dissection for testicular cancer is associated with a desmoplastic reaction that renders retroperitoneal surgery more challenging. We examined the impact of seminomatous elements on the rate of complications and the need for additional intraoperative procedures in patients undergoing post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: The testis cancer data base at our institution was retrospectively reviewed and 1,366 patients were identified who underwent post-chemotherapy retroperitoneal lymph node dissection between 1973 and 2001. In 97 patients there was an element of seminoma in the dissection specimen and/or pure seminoma in the testicular primary specimen (seminoma group). The remaining 1,269 patients underwent post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous testicular tumors. The rates of intraoperative complications and additional procedures as well as postoperative complications were analyzed. RESULTS: Of the 97 patients in the seminoma group 37 (38.1%) required a total of 47 additional intraoperative procedures, including 25 nephrectomies, 9 inferior vena caval resections, 5 arterial grafts, 5 bowel resections and 3 hepatic resections/biopsies, compared with 340 of the 1,269 patients (26.8%) in the group without seminomatous elements (p = 0.02). Postoperatively complications occurred in 24 of 97 patients (24.7%) in the seminoma group versus 257 of 1,269 (20.3%) in the group without seminomatous elements (p = 0.29). One of the 97 patients in the seminoma group died secondary to postoperative complications. CONCLUSIONS: A seminomatous element in patients undergoing post-chemotherapy retroperitoneal lymph node dissection is associated with a higher rate of additional intraoperative procedures and postoperative complications than in patients without seminomatous elements. However, resection is still possible with acceptable morbidity when indicated in appropriately selected patients.

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APMIS. 2003 Jan;111(1):64-8; discussion 68-9.
Diagnosis and management of testicular intraepithelial neoplasia (carcinoma in situ)--surgical aspects.
Dieckmann KP, Classen J, Loy V.
Department of Urology Albertinen-Krankenhaus Hamburg, Germany. DieckmannKP@t-online.de

Germ cell tumours (CT) are no true carcinomas; therefore the term testicular intraepithelial neoplasia (IN) is probably more appropriate than "CIS". The diagnostic accuracy of a single-site biopsy is an open question. We experienced 9 false-negative biopsies among 1859 cases. Thus, the proportion of a failed diagnosis is 0.5%. The main reason for diagnostic failure is the non-random distribution of TIN within the testicle. Currently we are investigating whether a two-site biopsy is more accurate than a single biopsy. In the ongoing trial, the over-all prevalence of TIN is around 5.3%, so far. In one quarter of the positive cases the lesion was found in only one of the two specimens. Thus, a double biopsy appears to be more favourable than the traditional single biopsy. Surgical complications amount to 2.5% in that double biopsy study. Only one surgical re-intervention was required among 983 patients. Serial imaging studies with scrotal sonography and magnetic resonance imaging (MRI) disclosed a transient intratesticular haematoma/oedema postoperatively. So, testicular biopsy, even when performed at two sites is in fact a low-complication procedure. Low dose radiotherapy to the testis is the treatment of choice for TIN. However, more than one quarter of patients require testosterone supplementation secondary to androgen-deficiency. Two dose-reduction studies (Denmark and Germany) had to be terminated prematurely because unexpected relapse of TIN was encountered at 14 Gy and 16 Gy. Possibly, hyperfragmentation schedules can overcome the antagonism of androgenic compromise and oncological safety. In a nation-wide survey, it was shown that contralateral biopsies were routinely performed in 66% of the urological departments in Germany. Another 19% offered the biopsy to particular "risk-cases"; only 15% never did a biopsy. Among those refusing biopsies, there was a higher proportion of small hospitals and a significantly lower annual case-number of GCT, when compared to those doing the biopsy. Thus, the contralateral biopsy is a well-established procedure among German urologists; those with a high caseload of GCT particularly appreciate it.

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Cancer. 2003 Apr 15;97(8):1981-4.
Primary transcrotal excision for paratesticular rhabdomyosarcoma: is hemiscrotectomy really mandatory?
Dall'Igna P, Bisogno G, Ferrari A, Treuner J, Carli M, Zanetti I, Guglielmi M, Cecchetto G.
Department of Pediatrics, Division of Pediatric Surgery, University of Padua, Italy. dalligna@child.pedi.unipd.it

BACKGROUND: To evaluate the role of primary reexcision (PRE) with scrotal resection in patients with paratesticular rhabdomyosarcoma enrolled in the German-Italian Cooperative Studies. The authors compared patients who underwent this procedure, according to the protocol guidelines, with those who did not. METHODS: In 32 of 198 patients with localized disease, the primary surgery was performed through a noncorrect scrotal approach. Twenty-four patients underwent PRE as recommended by the protocol guidelines (Group A) and 8 did not receive this treatment (Group B). The Group B patients were treated with the same chemotherapeutic regimens as the Group A patients and no radiotherapy was given to either group. RESULTS: After PRE, residual tumor was not detected in 21 of the 24 Group A patients. Twenty patients are alive in first complete remission 26-250 months after diagnosis (median, 40 months), 2 are alive in second complete remission at 3 and 9 months from diagnosis of lymph node and lung recurrence, and 2 died of disease after lymph node and distant metastases at 16 and 13 months from diagnosis. Three-fourths of these patients were older than 10 years old and the tumor was larger than 5 cm. The eight Group B patients are all alive in first complete remission 24-250 months since diagnosis. CONCLUSIONS: The data on the eight patients who obtained local control without PRE or radiotherapy warrant further investigation. Because of the supposed high risk of contamination with subsequent microscopic residual tumor after a transcrotal approach, we emphasize the utility of PRE with hemiscrotectomy. Copyright 2003 American Cancer Society.

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J Clin Oncol. 2003 Mar 15;21(6):1101-6.
Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial.
Classen J, Schmidberger H, Meisner C, Souchon R, Sautter-Bihl ML, Sauer R, Weinknecht S, Kohrmann KU, Bamberg M.
Departments of Radiation Oncology and Medical Information Processing, University of Tubingen, Tubingen, Germany. johannes.classen@med.uni-tuebingen.de

PURPOSE: A prospective multicenter trial was initiated to evaluate the role of modern radiotherapy with reduced treatment portals for stage IIA and IIB testicular seminoma. PATIENTS AND METHODS: Patients with stages IIA/B disease (Royal Marsden classification) were assessable for the trial. Staging comprised computed tomography of the chest, abdomen, and pelvis as well as analysis of tumor markers alpha-fetoprotein and beta human chorionic gonadotropin. Linac-based radiotherapy was delivered to para-aortic and high ipsilateral iliac lymph nodes. The total doses were 30 Gy for stage IIA and 36 Gy for stage IIB disease. RESULTS: Between April 1991 and March 1994, 94 patients were enrolled for the trial by 30 participating centers throughout Germany. Seven patients were lost to follow-up. Median time to follow-up of 87 assessable patients was 70 months. There were 66 stage IIA and 21 stage IIB patients. One mediastinal and one field-edge relapse were observed in the stage IIA group. In the stage IIB group, there was one mediastinal and one mediastinal/pulmonary relapse. All patients were treated with a salvage regimen of platinum-based chemotherapy. Actuarial relapse-free survival at 6 years was 95.3% (95% confidence interval [CI], 88.9% to 100%) and 88.9% (95% CI, 74.4% to 100%) for stage IIA and IIB groups, respectively. Maximum acute side effects were 8% grade 3 nausea for stage IIA and 10% grade 3 nausea and diarrhea for stage IIB groups. No late toxicity was observed. CONCLUSION: Radiotherapy for stages IIA/B seminoma with reduced portals yields excellent tumor control at a low rate of acute toxicity and no late toxicity, which supports the role of radiotherapy as the first treatment choice for these patients.

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Oncology (Huntingt). 2003 Feb;17(2):218-28; discussion 228-9, 234-5, passim.
Testicular cancer: maintaining the high cure rate.
Raghavan D.
Division of Oncology, USC Norris Cancer Center, University of Southern California, Los Angeles, California, USA. draghava@hsc.usc.edu

The management of germ cell tumors has advanced dramatically, with cure rates approaching 90% to 95%. Treatment of stage I/A seminomas generally includes orchiectomy and adjuvant radiotherapy. Treatment of stage I/A nonseminomatous germ cell tumors involves orchiectomy followed by retroperitoneal lymph node dissection or active surveillance. One of the major advances has been the introduction of cisplatin-based chemotherapy for metastatic disease and the development of a system of risk attribution. The logical management of any patient with curable disease is to provide curative therapy and then follow the patient in a structured manner, to diagnose and treat any complications in a timely manner.

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J Urol. 2003 Apr;169(4):1353-6.
Repeat retroperitoneal lymph node dissection for metastatic testis cancer.
Sexton WJ, Wood CG, Kim R, Pisters LL.
Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

PURPOSE: We report pathological results, perioperative complications and patient outcome in 21 men after repeat retroperitoneal lymph node dissection for metastatic testis cancer. MATERIALS AND METHODS: We reviewed an institutional tumor registry at our cancer center and identified 417 patients who underwent retroperitoneal lymph node dissection for testis cancer during a 21-year period. Of these 417 patients 21 underwent repeat retroperitoneal lymph node dissection. We reviewed preoperative patient characteristics, operative data and pathological findings from repeat lymphadenectomy, and determined patient disease status, morbidity and mortality after surgery. RESULTS: We identified viable germ cell tumor in 5 patients (24%), teratoma in 14 (67%) and fibrosis or necrosis only in 5 (24%). Intraoperatively subadventitial dissection of the aorta occurred in 2 cases, which was severe enough in 1 to require an aortic graft. The most common postoperative complications were prolonged ileus or partial bowel obstruction and chylous ascites in 6 and 3 patients, respectively. Six patients died, including 5 of disease progression and 1 of postoperative pulmonary embolus. At a mean followup of 4.7 years (range 0.1 to 14) 15 patients (71%) were alive and 14 (67%) were disease-free. CONCLUSIONS: Repeat retroperitoneal lymph node dissection is safe and effective in the majority of patients with recurrent or residual retroperitoneal masses after initial multimodality treatments for metastatic testis cancer. Overall perioperative morbidity and mortality are low and yet the potential for significant vascular complications warrants careful preoperative planning and intraoperative judgment.

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Gan To Kagaku Ryoho. 2003 Feb;30(2):171-80.
[Current status and future perspectives in chemotherapy for testicular cancer]
[Article in Japanese]
Kawai K.
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8575, Japan.

Approximately eighty percent of patients with disseminated testicular cancer can currently be cured because of the progress in cisplatin-based chemotherapy. For good risk disseminated disease, three courses of bleomycin, etoposide and cisplatin (BEP) is the most reliable induction chemotherapy. Cisplatin, ifostamide and either etoposide or vinblastine (VIP or VeIP) is effective standard-dose salvage chemotherapy, especially for relapsed patients with good prognosis features. However, remission is of short duration in many cases, resulting in an overall long-term disease-free survival rate of 10% to 25%. One possible approach to improve outcome is drug-dose increment. In recent years, high-dose chemotherapy (HDCT) with autologous stem-cell rescue has been used with some success in the first relapse cases and refractory cases. Although these non-randomized data are promising, the clinical benefit of HDCT remains to be confirmed in an ongoing randomized study. Another strategy is to include a new active drug in the chemotherapy regimen. Recent studies combining new active agents such as paclitaxel, gemcitabine and irinotecan have showed promising results in patients with poor prognostic disease or as salvage therapy.

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J Clin Oncol. 2003 Mar 1;21(5):871-7.
Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors.
Christian JA, Huddart RA, Norman A, Mason M, Fossa S, Aass N, Nicholl EJ, Dearnaley DP, Horwich A.
Academic Department of Radiotherapy and Oncology, Royal Marsden Hospital, Sutton, Surrey, United Kingdom. j.christian@icr.ac.uk

PURPOSE: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. PATIENTS AND METHODS: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. RESULTS: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). CONCLUSION: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

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Br J Cancer. 2003 Jan 13;88(1):36-41.
Excessive annual BMI increase after chemotherapy among young survivors of testicular cancer.
Nord C, Fossa SD, Egeland T.
Department of Medical Oncology and Radiotherapy, University Hospital, The Norwegian Radium Hospital (NRH), Oslo, Norway. carina.nord@klinmed.uio.no

Increased body mass index (BMI) is claimed to be a complication among survivors of testicular cancer (TCSs), especially after receiving cisplatin-based chemotherapy. This study compares changes in BMI (kg m(-2)) in TCSs with those observed in age-matched men from the population (controls). Associations between treatment, age and potential BMI changes were sought. In 1999, a survey was performed at the NRH of 444 unilaterally orchiectomised TCSs treated from 1980 to 1990. BMI at survey was recorded in each TCS. Information on principal treatment (surgery only: SURG; radiotherapy only: RAD; chemotherapy +/- surgery or radiotherapy: CHEM+/-) and pretreatment BMI was retrieved from the medical records. The age-matched controls had BMI measurements from population surveys from 1985 and 1996. The annual BMI increase was calculated based on the difference in the two BMI measurements divided by observation time. TCSs displayed a lower pretreatment mean BMI than the controls, whereas no difference was found post-treatment. However, the annual BMI increase in TCSs exceeded that of the controls (0.19 vs 0.15, P=1.4 x 10(-7)). The SURG and CHEM+/- groups showed the greatest annual BMI increase. The multiple regression analysis showed that young TC patients who received chemotherapy displayed an excessive annual BMI increase. Oncologists and young TCSs should be aware of the risk of excessive BMI increase, in particular, after the use of chemotherapy.

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Ginekol Pol. 2002 Oct;73(10):845-52.
[Sperm evaluation in testicular cancer patients before and after chemotherapy]
[Article in Polish]
Demkow T, Faundez R, Kamoda J.
Kliniki Nowotworow Ukladu Moczowego Centrum Onkologii-Instytutu w Warszawie.

OBJECTIVES: Over the last 20 years treatment results of testicular cancer have improved. At present, up to 90% of patients are cured. DESIGN: Semen analysis has been performed in 50 patients before and 3, 6, 12, 12, 18, 24, 30 months after i.t. MATERIALS: 50 Patients with testicular cancer underwent chemotherapy based on cisplatin. Before and after treatment the semen analysis has been performed on each patients. The results of the patient groups have been compared to healthy group of men. RESULTS: The quality of the semen is much worse in the group with cancer compared to healthy controls. The deepest impairment of the spermatogenesis has been found 3 mounts after chemotherapy. CONCLUSIONS: Orchidectomy has no influence on sperm parameters. Semen analysis revealed normospermia in 30% of the patients. 30 months after chemotherapy.

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Semin Urol Oncol. 2002 Nov;20(4):262-71.
The role of adjunctive postchemotherapy surgery for nonseminomatous germ-cell tumors: current concepts and controversies.
Sheinfeld J.
Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Adjunctive surgical resection of residual disease after chemotherapy is a critical part of the comprehensive management of patients with advanced nonseminomatous germ-cell tumor (NSGCT). Surgical resection is indicated in the presence of residual radiographic abnormalities and normal serum tumor markers. Necrosis, teratoma, and viable carcinoma can be found at any resected site. After induction chemotherapy, necrosis comprises approximately 50% of histologic findings, teratoma 40%, and viable GCT the remaining 10%. A number of investigators have attempted to predict the presence of necrosis in an effort to obviate surgery. A number of variables predictive of necrosis have been identified and tested prospectively, including: degree of tumor shrinkage, size of pre- and posttreatment mass(es), prechemotherapy markers, and teratomatous components in the orchiectomy specimen. However, the risk for a false-negative prediction remains approximately 20%. The most rigorous approach remains a retroperitoneal lymph node dissection (RPLND). Furthermore, the histologic discordance between different sites ranges from 29% to 46%; thus, all sites of residual disease should be resected. The patient's prognosis is influenced by: (1) completeness of resection, and (2) biology of the tumor (histology of residual mass(es), marker status at the time of RPLND, and prior burden of therapy). Surgical boundaries and completeness of dissection should not be compromised in an attempt to preserve ejaculation. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Semin Urol Oncol. 2002 Nov;20(4):251-61.
Poor prognosis germ-cell tumors: An unresolved challenge.
Toner GC, Frydenberg M.
Department of Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia.

The prognostic classification developed by the International Germ Cell Consensus group (IGCCC) enables appropriate choice of initial treatment, and provides consistent eligibility criteria for clinical trials and more accurate assessment of published results. The standard therapy for IGCCC poor- and intermediate-prognosis germ-cell tumors is 4 cycles of bleomycin, etoposide, and cisplatin chemotherapy followed by surgical resection of residual masses, if the serum tumor markers have returned to normal. Improved outcomes are achieved by centers that treat a larger number of cases. The unsatisfactory results achieved with current therapy warrant entry of these patients into appropriate clinical trials. Future improvements in therapy are likely to require a better understanding of the molecular mechanisms of resistance and the development of novel therapeutic approaches that target these mechanisms. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Semin Urol Oncol. 2002 Nov;20(4):244-50.
Chemotherapy for good-risk germ-cell tumors.
Ryan CJ, Bajorin DF.
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.

Patients with good-risk germ-cell tumors have a high likelihood of cure with an approach that integrates cisplatin-based chemotherapy, surgery, radiation, and observation. This article addresses risk group allocation as well as the controversies regarding the composition, number of cycles, and dosages of chemotherapy regimens used in this population. Recent data from randomized trials demonstrate that carboplatin is inferior to cisplatin and that the dose of etoposide should be 500 mg/m(2) per course. Bleomycin remains controversial in good-risk germ-cell tumors, but the literature suggests that both E(500)P for four cycles or BE(500)P for three cycles may be considered standard. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Semin Urol Oncol. 2002 Nov;20(4):239-43.
Adjuvant chemotherapy for stage II nonseminomatous germ-cell tumors.
Kondagunta GV, Motzer RJ.
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Management options for patients with stage II nonseminomatous germ-cell tumors (NSGCT), completely resected at retroperitoneal lymph node dissection (RPLND), include 2 cycles of adjuvant cisplatin-based chemotherapy, or close surveillance, with chemotherapy reserved for patients who relapse. Both options are associated with cure in an equally high percentage of patients. The decision to choose one of these options over the other is influenced by the extent of the tumor resected and patient compliance. Surveillance is a strong consideration for patients with low-volume nodal disease at RPLND (pN1), because the relapse proportion is 30% or less. In contrast, patients with high-volume nodal involvement at RPLND (pN2) have a relapse rate of 50% to 90% with surveillance alone. Adjuvant chemotherapy is the preferable option in the latter group. A prospective trial of 2 cycles of etoposide plus cisplatin adjuvant chemotherapy for patients with pN2 tumors showed that this regimen was highly effective in achieving relapse-free survival. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Arch Esp Urol. 2002 Oct;55(8):927-36.
[Urologic treatment of testicular germ cell cancer]
[Article in Spanish]
Fernandez Gomez JM, Escaf Barmadah S, Guate Ortiz JL, Martin Huescar A, Fresno Forcelledo F, Garcia Rodriguez J, Rodriguez Faba O, Jalon Monzon A, Rodriguez Martinez JJ.
Servicio de Urologia I, Hospital Covadonga, Hospital Central de Asturias, Facultad de Medicina, Universidad de Oviedo, Oviedo, Espana.

OBJECTIVE: To review the treatment of testicular germ-cell cancer in our series. METHODS: 73 cases with the diagnosis of germ-cell testicular tumours were reviewed. All cases underwent orchiectomy and extension study with abdominal CT-scan and either chest X-ray or Thoracic CT-scan. We reviewed the treatment options employed in our series, analysing different currently recognised risk factors. RESULTS: 34 out of 73 testicular germ-cell tumours were seminomas (46.6%) and 39 non seminomas (54.4%). Clinically 58.9% of the patients had localised, stage I tumours. 85.7% seminomas were stage I at presentation compared to 35.9% (14) non seminomatous tumours. The remainder tumours presented in advanced phases (stages II & III). Inguinal orchiectomy was performed in all cases except 5 patients in whom tumours were incidentally diagnosed (atrophic testis orchiectomy, hydrocelectomy, trauma) and underwent ipsilateral scrotal excision in a second time. Lymphadenectomy was initially performed in 3 patients with non seminomatous tumours. Radiotherapy was used in 23 cases of seminoma (67.6%), although this percentage has been progressively reduced in recent years. 30 patients received chemotherapy after orchiectomy: 3 metastatic seminomas (stage II) (8.8% of seminomas treated with chemotherapy) and 27 non seminomatous tumours (69.2% of them). All metastatic tumours are among the last (25) (Stages II & III) and 2 stage I non seminomatous tumours. All seminomas achieved complete response without later relapse after a median follow-up of 50 months (12-145 months). Median follow-up for non seminomatous tumours was 57 months (1-288 months). 13 non seminomas had relapses (33.3%). Relapses appeared in the retroperitoneum in 11 cases (84.6%), 2 of them concurrent with pulmonary relapse; 1 patient had liver relapse, one lung and another in bone. Median time to relapse was 4 months (2-102). 8 patients died and 2 were lost for follow-up. CONCLUSIONS: Testicular germ-cell cancer needs a well established multidisciplinary approach, in which the role of the urologist is fundamental. Orchiectomy is the primary treatment and allows determination of the dissemination risk. Radiotherapy is very effective for localised seminomas with poor prognostic factors, and for non seminomas 2 cycles of chemotherapy seem to be an effective approach, as well as of little toxicity. We must know and apply optimised programs for observation of these tumours (stage I), and also use follow-up protocols after chemotherapy or radiotherapy. Some cases need complex surgery for residual masses resection or post chemotherapy salvage surgery in disseminated tumours (Stages II & III). Sterility treatment protocols are applied to preserve fertility.

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Int J Urol. 2002 Oct;9(10):539-44.
Nerve-sparing retroperitoneal lymph node dissection for advanced testicular cancer after chemotherapy.
Nonomura N, Nishimura K, Takaha N, Inoue H, Nomoto T, Mizutani Y, Nakao M, Okuyama A, Miki T.
Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Suita, Japan. nono@uro.med.osaka-u.ac.jp

BACKGROUND: Nerve-sparing techniques are commonly used in retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular germ cell tumors to preserve postoperative ejaculation. The indications for nerve-sparing procedures have been extended to patients who have residual retroperitoneal tumor postchemotherapy with an increase in the incidence of local recurrence. Here, we report on 26 Japanese men with advanced testicular cancer who underwent nerve-sparing RPLND after partially successful chemotherapy. METHODS: Between January 1995 and December 2000, 26 patients with metastatic or recurrent testicular cancer underwent nerve-sparing RPLND after chemotherapy. Eight patients had seminoma and 18 had non-seminoma. Three patients received high-dose chemotherapy with carboplatin (250 mg/m2 per day x 5 days), etoposide (300 mg/m2 per day x 5 days) and ifosfamide (1.5 g/m2 per day x 5 days) in combination with peripheral blood stem cell transplantation. RESULTS: In all cases, lumbar splanchnic nerves were preserved macroscopically during the operation, at least unilaterally. Twenty-two patients (84.6%) achieved antegrade ejaculation during a mean follow-up at 3.9 months (range: 1-7 months). Three patients have fathered children. Only one patient suffered a retroperitoneal recurrence during a median follow-up at 25.8 months (range: 6-76 months). CONCLUSION: Nerve-sparing procedures for RPLND are appropriate for patients with metastatic testicular cancer, even after chemotherapy. The procedure preserves ejaculatory function in the majority of the patients without increasing the risk of local recurrence. Nerve-sparing RPLND improves the quality of life in patients who require postchemotherapy RPLND to treat residual tumor.

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Bull Cancer. 2002 Oct;89(10):877-85.
Management of advanced seminoma: retrospective study of 96 patients]
[Article in French]
Bompas E, Flechon A, Biron P, Droz JP.
Unite d'oncologie medicale, Pavillon E, Hopital edouard-Herriot, 5, place d'Arsonval, 69437 Lyon Cedex 03, France.

AIM OF THE STUDY: We report the results of a retrospective study in 96 patients with advanced seminoma, who received first line chemotherapy at the centre Leon-Berard from 1980 to 2000. PATIENTS AND METHODS: The primary site of disease was gonadonal in 88 patients and extragonadal in 8 others. Among the 96 patients, 8 patients had an atypic seminoma and 88 a classical seminoma. Extranodal metastases were present in 25 patients, metastatic site was unique in 69 patients. Except 9 patients, all had a good prognosis according to the IGCCCG. All patients had normal serum AFP level at diagnosis. Ten and 38 patients had elevated hCG and LDH serum marker level respectively. RESULTS: After first line chemotherapy, 18 patients achieved a complete response (CR) and 73 a marker negative partial response (PR-). Two presented a marker positive partial response (PR+), and two others, a progressive disease (PD). One toxic death occurred after first cycle of chemotherapy. Seventy-seven patients had residual masses. Resection was performed in 27 patients with PR- and led to 18 CR. Only two of the 27 residual mass contained active tumor. After chemotherapy and additional treatment as surgery or radiotherapy, a residual mass was still present in 55 patients but disappeared spontaneously for 23 of them. Relapse occurred in 18 patients, 16 of whom received salvage chemotherapy. A favourable response was observed in 9 patients with 6 complete responses. Despite this treatment, 14 patients eventually died. No adverse prognostic factor such as primary extragonodal site, prior radiotherapy, number of metastastic sites, international classification, serum markers levels (hCG, LDH) was found. The 5-years overall survival rate was 78%. CONCLUSION: This study show the poor outcome of patients with advanced seminoma after relapse. Renewed efforts are required to identify specific markers in seminoma in order to optimize treatment at initial presentation. Spontaneous regression of residual mass is frequent, thus an observation can be proposed without indication of immediate additional treatment, as surgery.

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Crit Rev Oncol Hematol. 2002 Oct;44(1):71-80.
The role of retroperitoneal surgery in testis cancer.
Leisinger HJ, Donohue JP.
Department of Urology, University Hospital, CH-1011 Lausanne, Switzerland. hans-jurg.leisinger@chuv.hospvd.ch

Testis cancer is today a curable malignancy. But controversy remains about the appropriate management of patients presenting different stages. There is an increasing interest in surveillance rather than in primary retroperitoneal lymph node dissection (RPLND) for stage I non-seminomatous germ cell tumors (NSGCT). Adjuvant chemotherapy has become an efficient treatment option for high risk non-seminomatous germ cell testis cancer, however, biological and histologic risk factors of the primary tumor are not yet precisely defined. To determine the appropriate management of patients with testicular cancer, postoperative morbidity after RPLND and risk of chemotherapy-induced morbidity must be balanced. Whoever reviews the literature must take into consideration that the excellent postoperative results after RPLND depend on high volume and large experience with testis cancer. As treatment morbidity and its intensity have a major impact on testis cancer patient quality of life, the choice of management must be based on the patient's social situation, his personal needs, and the doctor's experience and resources.

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Urologiia. 2002 Jul-Aug;(4):10-4.
[Testicular sertolioma]
[Article in Russian]
Gurarii LL, Volkova MI, Khalaf'ian EA, Zakharova TI.

Sertolioma accounts for 4.5% of all non-herminogenic testicular tumors. Sertolioma presents clinically with local symptoms (enlarged testis) which may be associated with dyshormonal symptoms. Most sertoliomas are benign, only 16.7% of them are malignant. Metastatic process is primarily lymphogenic and involves first retroperitoneal lymph nodes. Accurate histological criteria of malignancy for sertolioma have not been determined yet. The treatment should be started with orchofuniculectomy. Organ-saving operations may be performed in metastases-free children with bilateral sertoliomas. Surgical treatment is the only treatment effective in malignant sertolioma. Retroperitoneal and (or) solitary distant metastases should be removed surgically. Sertolioma is resistant to chemotherapy and is low sensitive to radiotherapy. Contrary to benign sertolioma, malignant one has poor prognosis.

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Curr Opin Urol. 2002 Sep;12(5):435-40.
Surgery in testis cancer: laparoscopic and open techniques.
Albers P.
Department of Urology, Bonn University, Bonn, Germany. peter.albers@ukb.uni-bonn.de

PURPOSE OF REVIEW: The review focuses on the current developments of the management of patients with testis cancer regarding surgery. For clinical stage I and stage II disease, the pros and cons of surgery as a diagnostic and therapeutic tool are updated. Additionally, the emerging role of laparoscopic techniques in the staging of the disease is critically discussed. The review presents the currently changing indications for surgery in addition to chemotherapy in metastatic disease. RECENT FINDINGS: The complication rates of primary retroperitoneal lymph node dissection have recently been assessed by the German Testicular Cancer Study Group. These data confirm the excellent results of the Indiana series published some years ago. Laparoscopic surgery has been performed in a larger cohort of patients in specialized centers, and, concomitantly, operative times and complication rates have dropped. Indications for surgery in the post-chemotherapy setting have been more clearly defined recently. Seminoma patients usually do not need surgical removal of the residual tumor after chemotherapy, whereas patients with non-seminoma disease probably need surgery even in cases of complete radiological remission after chemotherapy. In view of the recent data on late relapse, complete surgical removal of residual disease for non-seminoma seems of the utmost importance. SUMMARY: Larger series of surgical procedures, laparoscopic as well as open, have helped to define the role of this approach in the management of testis cancer. Long-term data on patients with complete response to initial treatment and late relapse have shown the danger of limiting the treatment of metastatic disease to chemotherapy alone. These data have also shown the importance of proper surgical techniques for all stages of testis cancer.

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Curr Opin Urol. 2002 Sep;12(5):427-30.
Clinical stage I nonseminomatous testicular germ-cell tumors: surgery or watchful waiting, still an issue?
Heidenreich A.
Department of Urology and Pediatric Urology, Philipps - University, Marburg, Germany. heidenre@post.med.uni-marburg.de

PURPOSE OF REVIEW: The optimal management for clinical stage I nonseminomatous testicular germ-cell tumors is still a subject open to controversy. The main options of standard-care surveillance and primary nerve-sparing retroperitoneal lymph node dissection result in the same high cure rate (close to 100%). It is the purpose, here, to present a critical review of recent developments concerning primary therapy for clinical stage I nonseminomatous testicular germ-cell tumors and to identify potential new prognostic risk factors predicting occult metastatic retroperitoneal lymph node disease. RECENT FINDINGS: In accordance with the primary goal to improve quality of life, to protect fertility and to reduce long-term toxicity in survivors of testicular cancer, the major advantage of surveillance protocols is that adjuvant therapy will be administered only to those patients who require therapy. This advantage has to be balanced against a constant psychological threat and a relapse rate of 20-25% necessitating extensive polychemotherapy. Primary nerve-sparing retroperitoneal lymph-node dissection has diagnostic and therapeutic capabilities in low-volume disease; as local relapses are extremely rare, an effective and cost-saving follow-up concentrating on pulmonary recurrences can be initiated. Nerve-sparing retroperitoneal lymph node dissection represents the initial approach for mature teratomas; patients with purely embryonal carcinoma have a high risk for systemic relapses and might be better served by primary chemotherapy. The advantages of nerve-sparing retroperitoneal lymph-node dissection have to be balanced against surgery-related complications, which develop in about 17% of the patients. With regard to prognostic risk factors, the percentages of embryonal carcinoma and vascular invasion remain the most significant predictors for lymph node metastases. SUMMARY: Surveillance and primary nerve-sparing retroperitoneal lymph-node dissection result in the same high cure rate (approaching 100%). The advantages and disadvantages of both treatment modalities must be discussed extensively with the patient, and it will be basically his decision as to which therapeutic approach is chosen.

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Cancer Treat Rev. 2002 Oct;28(5):237-53.
Treatment of testicular germ-cell cancer: a cochrane evidence-based systematic review.
Shelley MD, Burgon K, Mason MD.
Cochrane Unit, Research Department, Cardiff, Wales, UK. mike.shelley@velindre-tr.wales.nhs.uk

Testicular germ-cell cancer is relatively rare, affecting less than 6 men per 100,000 in the UK, nevertheless, it is the most common cancer in men under 45 years. The two main types of tumours, seminomas and non-seminomas, respond to treatment differently. The standard treatment for stage I seminomas following orchidectomy is infradiaphragmatic lymph node irradiation with response rates approaching 100%, although surveillance is also a management option. The majority of early stage non-seminomas are cured by orchidedctomy alone. Bleomycin, etoposide and cisplatin, (BEP) is the most widely used chemotherapeutic regimen for metastatic germ cell tumours. In patients with 'good prognosis' the current focus is to reduce the drug-related toxicity but maintain the cure potential. Most attempts using dose reduction or alternative regimens have not proved superior to BEP. In patients with 'poor prognosis' the aim has been to increase the efficacy of treatment using high-dose chemotherapy and investigate new regimens. This article comprehensively reviews the treatment of testicular germ cell cancer with emphasis on high-grade evidence from randomised controlled trials.

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Arch Ital Urol Androl. 2002 Jun;74(2):77-80.
Management of clinical stage I testicular pure seminoma. Report on 42 patients
and review of the literature.
Porcaro AB, Antoniolli SZ, Schiavone D, Maffei N, Bassetto MA, Curti P.
Cattedra e Divisione Clinicizzata di Urologia, Ospedale Policlinico G.B. Rossi, Verona, Italy.

INTRODUCTION: Testis cancer is the most common tumor detected in men aged from 20 to 35 years accounting for 1-2%. About 20-30% of patients presenting with clinical stage I pure seminoma of the testis, which accounts for 45-50% of all germ cell tumors, present with occult metastases in the retroperitoneal lymph nodes. Currently, treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant single agent chemotherapy. Herein, we review our experience in the management of 42 patients with clinical stage I pure seminoma of the testis and review the literature concerning this topic. MATERIALS AND METHODS: Between January 1977 and December 2000, of 56 patients with pure seminoma of the testis 42 (75%) were assessed as clinical stage I disease. Adjuvant RT was performed in 41 patients and surveillance in 1. Radiations fields included the para-aortic and ipsilateral pelvic lymph nodes. A radiation dose of 25 Gy in 20 daily fractions was given. All patients were followed up. RESULTS: Average age was 41.2 years (range 24-67). Mean follow-up was 85.3 months (range 12-279). Histopathology assessed classic seminoma in 41 cases (98%) and spermatocytic seminoma in 1 (2%). Small vessel invasion was detected in 8 cases (19%). Overall relapse rate was 4.7%. Overall survival rate resulted 97%. CONCLUSIONS: Adjuvant radiotherapy (RT) is a safe standard of care in controlling microscopic retroperitoneal disease in patients with clinical stage I seminoma. About 3 to 5% of patients undergo relapses, mostly after the first 18 months after orchiectomy. Overall cause-specific survival rates range between 96% to 100%. An alternative optional treatment for compliant patients presenting with low risk factors for relapse is surveillance with recurrences rates ranging between 15% to 20%. Surveillance avoids unnecessary treatment in about 80% of patients, thus it could be offered as a safe alternative option to adjuvant RT since imaging detects relapses at their early stages. Adjuvant chemotherapy with 1 or 2 courses of single-agent carboplatin is being investigated as an alternative adjuvant treatment to RT or surveillance in patients with moderate to high risk factors for relapse. The treatment is well tolerated and recurrence rate is 1%.

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Urology. 2002 Aug;60(2):324-8.
Long-term experience with carboplatin monotherapy for clinical stage I seminoma: a retrospective single-center study.
Steiner H, Holtl L, Wirtenberger W, Berger AP, Bartsch G, Hobisch A.
Department of Urology, University of Innsbruck, Innsbruck, Austria.

OBJECTIVES: To evaluate the long-term oncologic efficacy and morbidity of carboplatin monotherapy, which was introduced at our department 11 years ago for the treatment of Stage I seminoma. Radiotherapy is the standard treatment of patients with clinical Stage I seminoma. Carboplatin has been advocated as a treatment alternative to avoid the late side effects of radiotherapy and the high recurrence rate of surveillance strategies. METHODS: From February 1990 until August 2001, 108 patients received two adjuvant cycles of single-agent carboplatin (400 mg/m2 body surface on days 1 and 22) 2 weeks after high inguinal orchiectomy. To assess for myelosuppression, complete blood counts were performed at least once a week until the nadir occurred after the second treatment cycle. RESULTS: During a mean follow-up period of 59.8 months (range 6 to 134), 2 patients (1.85%) developed a recurrence (retroperitoneal tumor) within the first year. Both patients received cisplatin-based salvage chemotherapy. At last follow-up, all patients were alive without any evidence of disease. Carboplatin treatment was well tolerated by all patients and was associated with only mild gastrointestinal side effects. Leukopenia was noted in 32 patients (29.6%); 21 (19.4%) of these patients had World Health Organization (WHO) grade 1, 8 (7.4%) had grade 2, 3 (2.8%) had grade 3, and none had grade 4. No patient developed neutropenic fever. Thrombocytopenia was observed in 48 patients (44.4%); of these patients, 38 (35.2%) had WHO grade 1, 5 (4.6%) had grade 2, 2 (1.9%) had grade 3, and 3 (2.8%) had grade 4. CONCLUSIONS: From an oncologic standpoint, two cycles of carboplatin monotherapy was highly effective and very well tolerated by all patients.

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