Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous Testicular Cancer Research:
2002-2006   
The Testicular Cancer File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Testicular Cancer, click HERE.
 

Latest Research on
Testicular Cancer
     
J Clin Oncol. 2008 Aug 20;26(24):3937-42.
Influence of year of diagnosis, patient age, and sociodemographic status on recommending adjuvant radiation treatment for stage I testicular seminoma.
Hoffman KE, Chen MH, Punglia RS, Beard CJ, D'Amico AV.
Department of Radiation Oncology, Brigham and Women's Hospital, 375 Longwood Ave, Boston, MA 02115, USA. khoffman1@partners.org

PURPOSE: Adjuvant radiation therapy (ART) for stage I seminoma can cause adverse late effects and alternative postorchiectomy management strategies have been developed. This study evaluated ART trends in the United States and the impact of clinical and sociodemographic factors on ART recommendations. METHODS: Of men diagnosed with stage I seminoma from 1990 through 2004, 3,125 were identified using the Surveillance, Epidemiology, and End Results cancer registry. A multivariable logistic regression analysis was performed to assess whether there was a significant association between diagnosis year, diagnosis age, race, county education level, region, tumor size, tumor category, and the recommendation for ART. RESULTS: There was a significant association (P < .001) between later year of diagnosis and a decrease in ART recommendation. Compared with men diagnosed in 1990 to 1994, men diagnosed in 1995 to 1999, and 2000 to 2004 were less likely to have ART (adjusted odds ratio [OR], 0.63; 95% CI, 0.48 to 0.84; and OR, 0.49; 95% CI, 0.37 to 0.63, respectively). There also was a significant association (P < .001) between county education level and ART recommendation. Men residing in counties with the highest education level were more likely to receive ART than men residing in counties with the lowest education level (OR, 2.12; 95% CI, 1.59 to 2.82). Also, men older than 30 years were more likely to receive ART than men age 30 or younger (OR, 1.26; 95% CI, 1.03 to 1.55). CONCLUSION: ART recommendations for stage I seminoma are declining. Men in less educated regions and the youngest men were less likely to receive a recommendation for ART.

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AJR Am J Roentgenol. 2008 Aug;191(2):387-95.
The role of imaging in the diagnosis, staging, and management of testicular cancer.
Sohaib SA, Koh DM, Husband JE.
Department of Diagnostic Radiology, Royal Marsden Hospital, Down Rd., Sutton, Surrey SM2 5PT, England.

OBJECTIVE: The objective of this article is to describe recent developments in imaging patients with testicular germ cell tumors (GCTs). CONCLUSION: Most patients with testicular GCTs can now be expected to be cured, so the focus on management moves toward identifying patients who need more aggressive treatment and avoiding long-term complications. CT remains central in the selection of a management strategy, although the roles of MRI and PET continue to evolve.

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Anticancer Res. 2008 Jul-Aug;28(4C):2317-20.
Complete response after imatinib mesylate administration in a patient with chemoresistant stage IV seminoma.
Pectasides D, Nikolaou M, Pectasides E, Koumarianou A, Valavanis C, Economopoulos T.
Second Department of Internal Medicine, Propaedeutic, Oncology Section, General Hospital Attikon, University of Athens, Haidari, Athens, Greece. pectasid@otenet.gr

The case of a young man with stage IV chemoresistant pure seminoma overexpressing KIT, who achieved complete remission (CR) after the administration of imatinib mesylate (400 mg once daily), along with a third-line chemotherapy regimen, consisting of paclitaxel (150 mg/m2), oxaliplatin (100 mg/m2) and gemcitabine (800 mg/m2) every 2 weeks with granulocyte colony-stimulating factor (G-CSF) support is reported. The patient had received first- and second-line regimens consisting of ifosfamide, bleomycin, etoposide cisplatin (5 cycles, every 3 weeks) and methotrexate, vinblastine, actinomycin D, cyclophosphamide, cisplatin (3 cycles, every 3 weeks) respectively, without having normalized beta-human chorionic gonadotrophin (beta-HCG) levels. Following treatment with imatinib plus third-line chemotherapy (paclitaxel, oxaliplatin, gemcitabine), the levels of beta-HCG were reduced to within the normal limits during the first month of treatment. Therefore, the patient underwent surgical resection of the residual disease from the retroperitoneum and liver, which proved to be only necrotic tissue. The patient is under close follow-up, with no evidence of disease, 36 months after the completion of chemotherapy and 32 months post surgery.

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Expert Rev Anticancer Ther. 2008 Jul;8(7):1081-90.
Exploration of treatment options for the management of stage I testicular seminoma.
Bernal F, Raman JD.
Department of Pediatric Oncology & Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Department of Pediatric Oncology, 44 Binney Street, Mayer 664, Boston, MA 02115, USA. fbernal@partners.org

Seminoma is the epitome of a highly treatable neoplastic malignancy. Approximately 80% of patients presenting with seminomatous germ cell tumors are diagnosed with stage I disease. Men with clinical stage I seminomas have an excellent chance of achieving a cure irrespective of the treatment option selected. With such high disease-specific survival rates, attention has turned to reducing treatment-related morbidity. Adjuvant radiotherapy to the para-aortic retroperitoneal lymph nodes in conjunction with orchidectomy has been the standard treatment since the mid-1990s. There is some evidence, however, suggesting potential deleterious long-term sequelae from radiation treatment. Adjuvant chemotherapy has gained support as an acceptable adjuvant treatment strategy for stage I seminoma. While long-term studies are limited, short-term data regarding the therapeutic efficacy of single-agent carboplatin are promising. Finally, surveillance following orchidectomy is an attractive option for motivated patients interested in avoiding immediate adjuvant therapy. It may be the optimal choice for compliant men who are able to handle the mental burden of not receiving active treatment.

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Anticancer Res. 2008 May-Jun;28(3A):1641-9.
Apoptosis regulation and spontaneous apoptosis index of testicular germ cell tumors are associated with differentiation and resistance to systemic treatment.
Mandoky L, Szende B, Géczi L, Bodrogi I, Kásler M, Bak M.
Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.

BACKGROUND: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ cell testicular tumors (GCT). Germ cells are particularly susceptible to apoptosis and it is reasonable to presume that GCTs are curable because of an intact and effective apoptotic pathway. PATIENTS AND METHODS: The expression of p53 and p21 was investigated in conjunction with the spontaneous apoptotic index in 20 refractory and 50 chemosensitive GCTs, with a complete follow-up. To detect a differentiation-dependent alteration in the apoptotic pathway, all of the histological tumor types were examined separately. RESULTS: Embryonal carcinoma components showed significantly higher p53 expression compared to other histological subtypes of GCTs. p21 was barely detectable in the majority of tumors. Seminomatous components showed no p21 expression. Mature teratomas and syncytiotrophoblasts showed significantly higher p21 expression than other tumor subtypes. Embryonal carcinomas showed significantly higher apoptotic indices than other non-seminomatous components. On the other hand, choriocarcinomas and mature teratomas showed the lowest spontaneous apoptotic potential. The apoptotic index correlated with the fraction of p53-positive cells, but not with the p21 expression rate. The refractory group showed significantly lower p53 expression, higher p21 expression and a higher apoptosis index than the sensitive group. CONCLUSION: Our results suggest that the p53 and p21 expression levels and the apoptosis index seem to be important factors in the issue of the chemosensitivity of GCTs. The protein expression pattern reflects a differentiation-dependent preference for G1/S-phase arrest in terminally differentiated syncytiotrophoblasts and mature teratoma cells, while p53 mediated apoptosis induction is meaning to less differentiated tumor types.

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Urology. 2007 Dec;70(6):1168-72.
Oncologic efficacy of laparoscopic RPLND in treatment of clinical stage I nonseminomatous germ cell testicular cancer.
Nielsen ME, Lima G, Schaeffer EM, Porter J, Cadeddu JA, Tuerk I, Kavoussi LR.
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2101, USA. nielsen@jhmi.edu

OBJECTIVES: To assess the oncologic efficacy of laparoscopic retroperitoneal lymph node dissection (LRPLND) for clinical Stage I nonseminomatous germ cell tumors (NSGCTs) in a large multi-institutional series. LRPLND is emerging as a less-invasive alternative in the adjuvant surgical treatment of patients with testicular cancer. METHODS: The medical records of 120 patients with clinical Stage I NSGCT who underwent LRPLND at one of four institutions in the United States were retrospectively analyzed. All patients had at least 12 months of postoperative follow-up. The modified template dissection was performed at all centers. For the purposes of analysis, the patients were divided into two groups: those with consonant clinical and pathologic Stage I disease (n = 74, 62%) and those upstaged to pathologic Stage II (n = 46, 38%). RESULTS: No patient, including those upstaged to pathologic Stage II disease undergoing surveillance (n = 10), presented with retroperitoneal recurrence after LRPLND. Two patients with consonant pathologic Stage I developed pelvic recurrence that was outside the standard dissection template. The median follow-up for the patients with pathologic Stage I was 28.5 months (range 12 to 144) and was 29 months (range 12 to 108) for those with pathologic Stage II. CONCLUSIONS: In this group of patients with clinical Stage I NSGCT, management at multiple institutions that included LRPLND provided excellent intermediate results, paralleling those historically achieved with open lymph node dissection.

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J Clin Oncol. 2007 Dec 20;25(36):5742-7.
Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German Testicular Cancer Study Group.
Hartmann JT, Gauler T, Metzner B, Gerl A, Casper J, Rick O, Horger M, Schleicher J, Derigs G, Mayer-Steinacker R, Beyer J, Kuczyk MA, Bokemeyer C; German Testicular Cancer Study Group.
Department of Oncology, South West German Comprehensive Cancer Center, Eberhard-Karls-University of Tuebingen, Otfried-Mueller-Str 10, 72076 Tuebingen, Germany. joerg.hartmann@med.uni-tuebingen.de

PURPOSE: To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features. PATIENTS AND METHODS: Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2, ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC. RESULTS: Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/microL and thrombocytes less than 25,000/microL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively. CONCLUSION: Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.

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J Clin Oncol. 2007 Dec 10;25(35):5597-602. Comment in: J Clin Oncol. 2007 Dec 10;25(35):5550-2.
Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular cancer.
Stephenson AJ, Bosl GJ, Motzer RJ, Bajorin DF, Stasi JP, 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 sheinfej@mskcc.org

PURPOSE Patients with clinical stage (CS) IIA and IIB nonseminomatous germ cell tumor (NSGCT) with adenopathy more than 2 cm, multiple masses, elevated serum tumor markers, or disease outside the primary landing zone have increasingly been recommended to receive primary chemotherapy over time at our institution. The impact of these selection factors on the outcome of patients managed primarily by retroperitoneal lymph node dissection (RPLND) or chemotherapy was examined. PATIENTS AND METHODS Between 1989 and 2002, 252 patients with CS IIA and IIB NSGCT were referred to our institution for initial management, of whom 136 underwent RPLND and 116 received chemotherapy and postchemotherapy RPLND. Patient information was obtained from a prospective RPLND database. Results Proportionately more patients received chemotherapy over time (22% in 1989 to 1993 v 68% in 1999 to 2002), and the relapse-free survival (RFS) subsequently improved from 84% (1989 to 1998) to 98% (1999 to 2002; P
= .004) without increasing the proportion who received any chemotherapy (70% v 79%; P = .16). By increasingly selecting patients with adverse features for primary chemotherapy, the RFS after RPLND improved from 78% to 100% (P = .019), but rates of pathologic stage II and retroperitoneal teratoma were unaffected. Retroperitoneal histology and RFS did not change over time for chemotherapy patients. Primary chemotherapy was associated with improved RFS compared with RPLND (98% v 79%; P < .001), but disease-specific survival did not differ significantly (100% v 98%; P = .3). CONCLUSION Patient selection factors have significantly improved the outcome of patients with CS IIA and IIB NSGCT without substantially increasing the proportion of patients exposed to chemotherapy.

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J Clin Oncol. 2007 Dec 10;25(35):5603-8. Epub 2007 Nov 12.
Improved clinical outcome in recent years for men with metastatic nonseminomatous germ cell tumors.
Carver BS, Serio AM, Bajorin D, Motzer RJ, Stasi J, Bosl GJ, Vickers AJ, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, 353 E 68th St, New York, NY 10021, USA. carverb@mskcc.org

PURPOSE: The integration of chemotherapy and surgery for metastatic nonseminomatous germ cell tumors (NSGCT) results in survival rates of greater than 80% overall. We evaluated men undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for NSGCT to determine associations between year of treatment and clinical outcome. PATIENTS AND METHODS: We evaluated 504 men who underwent PC-RPLND from 1989 to 2002 for NSGCT at our center. Data were obtained from our prospective surgical database and a multivariable logistic regression model was constructed to evaluate variables associated with 15-month relapse in 392 patients with complete data. RESULTS: From 1989 to 1997, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 4%, 20%, 23%, and 47% of patients, respectively, compared with 18%, 26%, 11%, and 38%, respectively, from 1998 to 2002 (P < .001). The median prechemotherapy nodal size for 1989 to 1997 and 1998 to 2002 was 5.0 and 3.5 cm, respectively (P < .001). On multivariable analysis, prechemotherapy retroperitoneal nodal size (odds ratio [OR], 1.12; 95% CI, 1.03 to 1.21; P = .005) and presence of visceral metastasis (OR, 2.10; 95% CI, 1.02 to 4.33; P = .04) were significantly associated with 15-month relapse. Men who received a complete RPLND were significantly less likely to experience relapse (OR, 0.22; 95% CI, 0.09 to 0.50; P < .0005). CONCLUSION: In more recent years, men are presenting with less advanced metastatic NSGCT. This stage migration together with effective therapy has resulted in an improved relapse-free survival.

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Ann Oncol. 2007 Nov 15 [Epub ahead of print]
Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group.
Bokemeyer C, Oechsle K, Honecker F, Mayer F, Hartmann JT, Waller CF, Böhlke I, Kollmannsberger C.
Department of Oncology/Hematology with sections Bone Marrow Transplantation and Pneumology, University Medical Centre Eppendorf, Hamburg, Germany.

BACKGROUND: The aim of this study is to determine feasibility and efficacy of the combination regimen gemcitabine, oxaliplatin, and paclitaxel (GOP) in patients with cisplatin-refractory or multiply relapsed germ-cell tumors. PATIENTS AND METHODS: From April 2003 to October 2006, 41 patients refractory to cisplatin-based chemotherapy or with relapse after high-dose chemotherapy (HDCT) plus stem-cell support (peripheral blood stem-cell transplantation: PBSCT) received 800 mg/m(2) gemcitabine, 80 mg/m(2) paclitaxel (Taxol), both on days 1 + 8, and oxaliplatin 130 mg/m(2) on day 1 of a 3-week cycle for a minimum of two cycles. Primary end point was response rate. Patients were pretreated with a median of two lines of platin-based chemotherapy (range, 1-3), and 78% had relapsed after HDCT/PBSCT. RESULTS: Seventy-three percent of patients had relapsed within 3 months after the last cisplatin-based chemotherapy. Five percent of the patients achieved a complete response, and 34% and 12% a marker-negative and marker-positive partial response, respectively (overall response rate 51%). After a median follow-up of 5 months (range, 0-20), 15% of the patients remain in complete remission after GOP chemotherapy +/- residual tumor resection with a median response duration of 8 months (1 to 17+). Main toxicity was leucocytopenia grade 3/4 in 15%, anemia in 7%, and thrombocytopenia in 49% of the patients. CONCLUSION: Combination chemotherapy with GOP is feasible and effective with acceptable toxicity in patients with treatment-refractory germ-cell tumors.

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Can J Urol. 2007 Oct;14(5):3692-6.
The importance of the dose of etoposide in the initial treatment of metastatic germ cell tumors and advances in management of patients that relapse.
Marwaha S, Venner PM, North SA.
University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Edmonton, Canada.

OBJECTIVE: The primary objective was to evaluate the effect of etoposide dose in a 3-day cisplatin/etoposide/bleomycin (PEB) regimen on progression free survival (PFS) and overall survival (OS). Secondary objectives were to determine the impact of a paclitaxel-based salvage regimen on OS and to compare the risk distribution of germ cell patients seen at a tertiary care center to that quoted in the International Germ Cell Consensus Classification (IGCCC). METHODS: A retrospective chart review of all 302 metastatic germ cell patients requiring cisplatin-based chemotherapy between January 1980 and December 2004 was conducted. Data collected on initial treatment included the dose of etoposide: 500 mg/m2/cycle (E500) or 360 mg/m2/cycle (E360) and whether the salvage treatment contained paclitaxel or not. PFS and OS were calculated. Patients were risk stratified as per IGCCC variables. RESULTS: The relapse rate and overall survival for E500 was 3% and 97% respectively compared to a relapse rate and OS rate of 29% and 80% respectively for E360. The addition of paclitaxel to salvage chemotherapy regimens for patients that relapsed results were 1/5 (20%) of patients dying compared to 26/39 (67%) for those who received a non-paclitaxel based salvage regimen. Ninety percent of seminoma patients were good risk and 10% were intermediate risk. Non-seminoma (NSGCT) patients were skewed to the good-risk category: 71% good risk, 10% intermediate risk and 18% poor risk as compared to 56%, 28% and 16% respectively as reported by the IGCCC. Five-year PFS and OS were comparable to those documented by the IGCCC with the exception of the intermediate risk NSGCT patients. CONCLUSION: This review demonstrated that PEB treatment containing higher dose etoposide was superior in terms of PFS and OS. Although the sample size was small, it appeared that paclitaxel containing salvage regimens resulted in superior outcomes compared to previously used salvage regimens. Our center had a similar risk distribution of patients as that quoted by the IGCCC.

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Tumori. 2007 Sep-Oct;93(5):428-31.
Late relapse in testicular germ cell tumors.
Detti B, Livi L, Scoccianti S, Meattini I, Gacci M, Lapini A, Biti G.
Institute of Radiotherapy, University of Florence, Florence, Italy. beatrice.detti@googlemail.com

AIMS AND BACKGROUND: Analysis of patients with late relapse of testicular germ cell tumors (GCTs) with reports on clinicopathological features and outcomes. METHODS: We identified all patients diagnosed with testicular GCTs at our Institute between 1988 and 2004 who developed relapse > or = 24 months after completion of primary therapy. A retrospective case-note review was performed to extract clinical, pathological, treatment and outcome data. RESULTS: Six patients (1.25%) developed late relapse. All patients presented with stage I disease and were classified as "good risk" according to the International Germ Cell Consensus Classification. Mean time to late relapse was 48 months. Markers at late relapse were normal in all patients. Relapse was confined to retroperitoneal sites in five patients and located in the mediastinum in one patient. Five patients were managed by chemotherapy alone while one underwent combined treatment with surgery followed by chemotherapy. All patien
ts obtained a complete response and all remained free from recurrence with a mean follow-up of 115 months. CONCLUSIONS: The incidence of late relapse in this small series is low. Chemonaive patients with late relapse were successfully salvaged with chemotherapy alone or surgical excision followed by cisplatin-based chemotherapy. The optimal duration of follow-up in patients with testicular GCTs is not known and practice varies widely. At our Institute we advise lifelong follow-up of all patients with malignant GCTs of the testis.

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Cancer. 2007 Sep 15;110(6):1235-40.
Is full bilateral retroperitoneal lymph node dissection always necessary for postchemotherapy residual tumor?
Beck SD, Foster RS, Bihrle R, Donohue JP, Einhorn LH.
Department of Urology and Oncology, Indiana University Medical Center, Indianapolis, Indiana.

BACKGROUND.: Traditionally, postchemotherapy (PC) surgery for metastatic nonseminomatous germ cell tumor (NSGCT) has used a full bilateral retroperitoneal lymph node dissection (RPLND) from the crus of the diaphragm to the bifurcation of the common iliac arteries, from ureter to ureter. With the primary landing zone well defined in low-volume retroperitoneal disease, the authors performed modified dissections in the PC setting in a select population; and, herein, they report disease outcome. METHODS.: From 1991 to 2004, a retrospective review of the testicular cancer database at the authors' institution was performed to identify patients with NSGCT, normal serum tumor markers after cisplatin-based chemotherapy, and residual retroperitoneal tumor who underwent modified PC-RPLND. All patients had metastatic disease at initial presentation that was limited to the primary landing zone (left or right). RESULTS.: One hundred patients were identified, including 43 who underwent a right modified template, 18 patients who underwent a left full modified template, and 39 patients who underwent a left modified template. Pathology revealed cancer in 2% of patients, teratoma in 62% of patients, and necrosis in 36% of patients. The 2- and 5-year disease-free survival rate was 95%, and the median follow-up was 31.9 months (range, 1-152 months). Four patients developed recurrent disease with a median time to recurrence of 8.25 months (range, 6-11 months). All recurrences were outside the boundaries of a full bilateral RPLND. CONCLUSIONS.: Selected patients at PC surgery can be managed with modified PC-RPLND. Cancer 2007. (c) 2007 American Cancer Society.

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Arch Pathol Lab Med. 2007 Aug;131(8):1267-80.
An overview of testicular germ cell tumors.
Bahrami A, Ro JY, Ayala AG.
Department of Pathology, Baylor College of Medicine, Houston, TX, USA.

CONTEXT: More than 90% of testicular neoplasms originate from germ cells. Testicular germ cell tumors (GCTs) are a heterogeneous group of neoplasms with diverse histopathology and clinical behavior. OBJECTIVE: To help the readers distinguish various subtypes of GCTs, to highlight the clinical manifestations and pathologic features of these tumors, and to review several newly developed immunohistochemical markers for GCTs. DATA SOURCES: Review of the pertinent literature and our experience. CONCLUSIONS: The etiology of GCTs is largely unknown. Cytogenetic studies suggest a different pathogenesis for each group of infantile/prepubertal GCTs, postpubertal GCTs, and spermatocytic seminoma. Unclassified intratubular germ cell neoplasia is the precursor of all GCTs, excluding spermatocytic seminoma and infantile/prepubertal GCTs. Seminoma, the most common GCT in adults, does not occur before 5 years of age. Spermatocytic seminoma, a tumor of elderly men, typically has an indolent clinical behavior, but rarely it undergoes sarcomatous transformation associated with an aggressive behavior. Embryonal carcinoma is the most common component in mixed GCTs. Eighty percent or more of embryonal carcinoma component and vascular invasion are recognized predictors of occult metastasis for clinical stage I mixed GCTs. Most patients with prepubertal yolk sac tumor, the most common pediatric GCT, have stage I disease at presentation. Most choriocarcinomas present with metastatic symptoms because of the propensity for rapid hematogenous dissemination. Teratomas in children regardless of maturity and dermoid cysts in adults are benign; in contrast, teratomas in adults have a malignant behavior. With appropriate therapy, the majority of testicular GCTs are curable.

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N Engl J Med. 2007 Jul 26;357(4):340-8.
High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors.
Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R.
Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, USA. leinhorn@iupui.edu

BACKGROUND: Metastatic testicular tumors that have not been successfully treated by means of initial chemotherapy are potentially curable with salvage chemotherapy. METHODS: We conducted a retrospective review of 184 consecutive patients with metastatic testicular cancer that had progressed after they received cisplatin-containing combination chemotherapy. We gave 173 patients two consecutive courses of high-dose chemotherapy consisting of 700 mg of carboplatin per square meter of body-surface area and 750 mg of etoposide per square meter, each for 3 consecutive days, and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells; the other 11 patients received a single course of this treatment. In 110 patients, cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin preceded the high-dose chemotherapy. RESULTS: Of the 184 patients, 116 had complete remission of disease without relapse during a median follow-up of 48 month
s (range, 14 to 118). Of the 135 patients who received the treatment as second-line therapy, 94 were disease-free during follow-up; 22 of 49 patients who received treatment as third-line or later therapy were disease-free. Of 40 patients with cancer that was refractory to standard-dose platinum, 18 were disease-free. A total of 98 of 144 patients who had platinum-sensitive disease were disease-free, and 26 of 35 patients with seminoma and 90 of 149 patients with nonseminomatous germ-cell tumors were disease-free. Among the 184 patients, there were three drug-related deaths during therapy. Acute leukemia developed in three additional patients after therapy. CONCLUSIONS: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease. Copyright 2007 Massachusetts Medical Society.

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Cancer Control. 2007 Jul;14(3):258-64.
Laparoscopic retroperitoneal lymph node dissection in the management of testis cancer.
Correa JJ, Politis C, Rodriguez AR, Pow-Sang JM.
Genitourinary Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

BACKGROUND: The surgical approach to management of testis cancer has been traditionally through an open incision, but in the last decade, several centers have reported their experience with laparoscopic retroperitoneal lymph node dissection (LRPLND). METHODS: We reviewed the English literature, summarized the outcomes, and included our initial experience with the LRPLND procedure. RESULTS: Improvements in operative time, complications, and morbidity have occurred as surgical experience has increased. The procedure is more challenging in postchemotherapy patients. Outcomes at our institute are comparable to reported series from other institutions, and LRPLND is our current procedure of choice for RPLND. CONCLUSIONS: LRPLND has been shown to be a safe, effective, minimally invasive procedure in the management of testicular cancer patients who require surgery to address the retroperitoneal lymph nodes.

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J Clin Oncol. 2007 Jul 1;25(19):2778-84.
Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group.
Lorch A, Kollmannsberger C, Hartmann JT, Metzner B, Schmidt-Wolf IG, Berdel WE, Weissinger F, Schleicher J, Egerer G, Haas A, Schirren R, Beyer J, Bokemeyer C, Rick O; German Testicular Cancer Study Group.
Department of Hematology, Universitätsklinikum Giessen und Marburg GmbH, Marburg, Germany.

PURPOSE: To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs). PATIENTS AND METHODS: Between November 1999 and November 2004, 230 patients were planned to be recruited in a prospective, randomized, multicenter trial comparing one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2, and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE; arm A) versus three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC; arm B). RESULTS: The study was stopped prematurely after recruitment of 216 patients as a result of excess treatment-related mortality in arm B. One hundred eleven (51%) of 216 patients were randomly assigned to sequential HDCT, and 105 (47%) of 216 patients were randomly assigned to single HDCT. Five (2%) of 216 patients had to be excluded because of non-GCT histologies at review. With a median follow-up time of 36 months, 109 (52%) of 211 patients were alive, and 91 (43%) of 211 patients were progression free. At 1 year, event-free, progression-free, and overall survival rates were 40%, 53%, and 80%, respectively, in arm A compared with 37%, 49%, and 61%, respectively, in arm B (P > .05 for all comparisons). Treatment-related deaths, mainly as a result of sepsis and cardiac toxicity, were less frequent in arm A (four of 108 patients, 4%) compared with arm B (16 of 103 patients, 16%; P < .01). CONCLUSION: We found no difference in survival probabilities between single HDCT using CE and sequential HDCT using CEC. Sequential HDCT was better tolerated and resulted in fewer treatment-related deaths.

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Biol Blood Marrow Transplant. 2007 Jul;13(7):778-89. Epub 2007 Apr 30.
Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: a center for international blood and marrow transplant research (CIBMTR) analysis.
Lazarus HM, Stiff PJ, Carreras J, Logan BR, Akard L, Bolwell BJ, Childs RW, Gale RP, Klein JP, Lill MC, Pérez WS, Stadtmauer EA, Rizzo JD.
University Hospitals of Cleveland, Cleveland, Ohio 44106, USA. hillard.lazarus@case.edu <hillard.lazarus@case.edu>

Tandem autotransplants are used to treat advanced testis cancer patients but their value compared to a single autotransplant is unknown. To evaluate the results of autotransplant in relapsed testicular/germ cell cancer, data from 300 patients undergoing autotransplants 1989-2002 were reported to the Center for International Blood and Marrow Transplant Research. We compared results for those patients intended to undergo tandem autotransplant procedures (N = 102) versus patients in whom a second autotransplant was not planned (N = 198). Five-year survival probability was 35% (95% confidence interval = 25%-46%) in the planned tandem transplant cohort compared to 42% (35%-49%) in the group not planned to have a second transplant (P = .29). Probability of progression-free survival at 5 years for these cohorts was 34% (25%-44%) and 38% (31%-45%), respectively (P = .50). The planned tandem autotransplant cohort had significantly more advanced disease at diagnosis and greater likelih
ood of cisplatin resistance. Patients intended to receive tandem transplants had a lower treatment-related mortality at 1 year (3% versus 10%, P = .02). Using propensity score analysis the planned tandem autotransplant cohort had significantly lower treatment-related mortality (P = .044) but no different risk of relapse (P = .541) compared to the planned single transplant cohort. Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better.

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Klin Padiatr. 2007 May-Jun;219(3):146-51.
Surgery in infants and children with testicular and paratesticular tumours: a single centre experience over a 25-year-period.
Tröbs RB, Krauss M, Geyer C, Tannapfel A, Körholz D, Hirsch W.
Kinderchirurgische Klinik, Marienhospital Herne, Ruhr-Universität Bochum, Widumer Strasse 8, 44627 Herne. ralf-bodo.troebs@marienhospital-herne.de

Testicular and even more paratesticular tumours in children are rare. The aim of the study is to characterise the spectrum of these lesions with focus on the feasibility and effectiveness of testis sparing surgery. Twenty-four boys treated between 1980 and 2004 at the University Leipzig Medical Centre were evaluated. At presentation patients were between 5 months and 18 years old (median 23 months). Generally a high rate of malignant or potentially malignant tumours was observed. The majority of these tumours occurred in the first three years of age. The spectrum of testicular tumours comprised 13 germ cell tumours (6 yolk sac tumours, 6 teratomas, 1 embryonal carcinoma) and 4 sex cord stromal tumours (2 Leydig's cell, Sertoli's cell, granulosa cell). Both Leydig's cell tumours were endocrine active. Further on, we observed 3 boys with paratesticular rhabdomyosarcoma (RMS), and three with testicular and paratesticular metastases (Wilms' tumour, neuroblastoma, leukaemia). Seru
m alpha1-fetoprotein (AFP) was clearly elevated in 5 of 6 yolk sac tumours but remained within normal limits concerning the other entities. Human chorionic gonadotrophin was normal in all cases tested. During the observation period high inguinal orchidectomy was the surgical standard method. Dependent on tumour histology, stage and the recommended treatment schedule postoperative chemotherapy was added. Testis sparing surgery was performed in 3 boys with primary testicular tumours (2 Leydig's cell, mature cystic teratoma). Local relapses were not observed. Systemic relapses occurred in 3 cases (2 RMS, leukaemia). During a median follow up of 5 years all patients with primary testicular tumours survived event free. Meta-analysis of the recent literature revealed that testis sparing surgery is feasible and save in prepubertal boys after exclusion of a malignant tumour. If a testis sparing approach is planned, the following criteria are essential: 1. The presence of a well defined circumscribed nodule confirmed by imaging. 2. Normal levels of serum AFP and hCG. 3. The presence of sufficient healthy testicular parenchyma. However, the high rate of malignant or potentially malignant tumours suggests that high inguinal orchidectomy should remain the surgical standard of therapy.

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Bull Cancer. 2007 May 1;94(5):439-48.
[Management of clinical stage I testicular germ cell tumours]
[Article in French]
Loriot Y, Fizazi K.
Institut Gustave Roussy, 39 rue Camille-Desmoulins, 94800 Villejuif. y.loriot@voila.fr

Testicular germ-cell cancer is the most frequent malignancy in young men. In 80% of case no metastasis is observed at diagnosis. Orchidectomy is the initial therapeutic intervention. In case of a pure seminoma, three treatment options should be discussed after surgery : radiotherapy with a limited dose and volume, surveillance, and chemotherapy by single-agent carboplatin. In non-seminomatous germ cell tumour three options should also be considered : surveillance, chemotherapy (two cycles of the BEP regimen) or retroperitoneal lymph node dissection. The strategy should be chosen taking into account predictive factors of relapse and the patient willing. Whatever the strategy, the cure rate is about 99%.

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Urol Clin North Am. 2007 May;34(2):137-48.
Management of clinical stage I nonseminomatous germ cell testicular cancer.
Choueiri TK, Stephenson AJ, Gilligan T, Klein EA.
Department of Solid Tumor Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, R35, Cleveland, OH 44195-0001, USA.

The optimal management of patients who have clinical stage I nonseminomatous germ cell tumors remains controversial. Surveillance, retroperitoneal lymph node dissection (RPLND), and chemotherapy with two cycles of bleomycin-etoposide-cisplatin are established treatment options and all are associated with long-term cancer control rates of 97% or greater. Studies have consistently identified the presence of lymphovascular invasion and a predominant component of embryonal carcinoma in the primary tumor as risk factors for occult metastatic disease in these patients. Patients who do not have these risk factors are optimally managed by active surveillance given the low risk for relapse. For patients at high risk for relapse and who are not candidates for surveillance, we believe the evidence supports RPLND over primary chemotherapy.

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Urol Clin North Am. 2007 May;34(2):199-217.
Role of post-chemotherapy surgery in germ cell tumors.
Sim HG, Lange PH, Lin DW.
Department of Urology, University of Washington, Box 356510, 1959 NE Pacific Street, Seattle, WA 98195, USA.

Surgery after systemic chemotherapy for advanced testicular cancer has maintained its role in staging and therapeutic management. The clinical outcome is strongly influenced by patient selection and extent of extirpative surgery. Although extensive predictive modeling has attempted to define appropriate post-chemotherapy surgical candidates based on various clinical and pathologic parameters, the accuracy of these models remains controversial. Complete removal of all post-chemotherapy residual masses in nonseminomatous germ cell tumors remains the standard of care and allows for improved prognostication of the long-term oncologic and functional outcome.

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Am J Clin Oncol. 2007 Apr;30(2):205-10.
Long-term outcome of stage I seminoma.
Yang GY, Li B, Wagner TD, Donohue KA, Flaherty L, Kuettel MR.
Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. gary.yang@roswellpark.org

PURPOSE: To report on long-term outcomes among patients with stage I seminoma treated by orchiectomy with or without adjuvant radiation. MATERIALS AND METHODS: A retrospective review of medical records of patients treated between 1974 and 2002 was undertaken to identify factors associated with patient outcomes. RESULTS: With a median follow-up of 7.7 years, 80% (4 of 5) of the surveillance group experienced a disease relapse, while only 3% (2 of 70) in the radiation therapy group had disease relapse. This difference in relapse rates was statistically significant, but there was no significant difference in overall survival between the 2 groups. There was a significant relationship between patient age and disease relapse, whereby all of the relapses were seen in patients younger than 36 years at diagnosis (P = 0.03). Of the total 75 patients, 7 (9%) developed second primary tumors. Six of them (6 of 7) were treated with adjuvant radiation, and 1 patient (1 of 7) was on surveillance. CONCLUSION: In this study, risk of relapse was significantly associated with surveillance and in patients younger than 36 years at diagnosis. These results suggest that surveillance can only be safely adopted for patients who can be followed up closely. We consider adjuvant radiation a very effective choice despite the low risk of associated secondary malignancies.

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Anticancer Drugs. 2007 Mar;18(3):273-6.
An open-label, multicenter phase II trial of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors.
Oechsle K, Honecker F, Kollmannsberger C, Rick O, Grunwald V, Mayer F, Hartmann JT, Bokemeyer C.
Department of Oncology/Hematology/Bone Marrow Transplantation/Pneumology, University Medical Center, Eppendort, Hamburg, Germany.

The objective of this multicenter phase II trial was to evaluate the efficacy and tolerability of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors. Between March 2003-June 2004, 14 patients refractory to at least two regimens of cisplatin-based chemotherapy or with relapse after high-dose chemotherapy and autologous peripheral blood stem cell transplantation received 1250 mg/qm capecitabine orally twice daily for 14 days in 3-week cycles. Treatment was continued until tumor progression. All patients were heavily pretreated with a median number of four previous lines of chemotherapy (range, 2-11) and 86% had relapsed after high-dose chemotherapy with peripheral blood stem cell transplantation. No patient responded to study treatment. Nine patients (64%) had progressive disease after two cycles. Two patients already stopped treatment after one cycle, because of a clinically overt tumor progression. One patient died of his tumor progression at the end of the second cycle. Two patients received four cycles of capecitabine, as progression was less than 30%. The median survival time was 4 months (range, 0-10). The toxicity profile was favorable. Eighty-six percent of the cycles could be applied without dose modifications or delay. Grade III/IV toxicities (diarrhea and anorexia in one patient each) occurred in 7% of the cases. No hematotoxicity grade III/IV was observed. Neutropenia grade I/II was documented in 21%, anemia in 35% and thrombocytopenia in 14% of the patients. Capecitabine was well tolerated, but is not effective in heavily pretreated patients with cisplatin-refractory or relapsed germ cell tumors.

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Rev Prat. 2007 Feb 28;57(4):389-98.
[Surgery of residual masses after chemotherapy in patients with testicular cancer]
[Article in French]
Flechon A, Rivoire M, Berger N.
Departement de cancerologie medicale, Centre Leon-Berard, Lyon. flechon@lyon.fnclcc.fr

Advanced non seminomatous germ cell tumours are rare diseases affecting young men. Advanced disease is curable in 80% of the cases. The primary site of metastases is the retroperitoneal lymph nodes. Secondary metastatic sites are the lungs and mediastinal lymph nodes. Cisplatin-based chemotherapy has dramatically improved the prognosis of germ cell tumours, but surgery, when applicable, remains a central part of treatment. Forty five per cent and 10% of residual masses contain teratoma or active disease respectively. Residual masses of pure seminoma are removed only when postoperative pet-scan evaluation is positive or when they have grown during the follow-up period. All surgical procedures must be performed in a reference center.

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J Endourol. 2007 Feb;21(2):180-3.
Long-term results of laparoscopic retroperitoneal lymph-node dissection for clinical stage I nonseminomatous germ-cell testicular cancer.
Neyer M, Peschel R, Akkad T, Springer-Stohr B, Berger A, Bartsch G, Steiner H.
Department of Urology, Medical University Innsbruck, Innsbruck, Austria.

PURPOSE: To report the long-term oncologic outcome and morbidity of laparoscopic retroperitoneal lymph-node dissection (L-RPLND) in clinical stage I nonseminomatous testicular germ-cell tumors (NSGCT) from a single institution. PATIENTS AND METHODS: From August 1992 to May 2005, 136 patients with clinical stage I disease underwent L-RPLND. The mean follow-up was 68 months (range 8-151 months). Patient selection was not based on histologic findings or the presence of risk factors. Lymphadenectomy was performed within the boundaries described by Weissbach and Boedefeld. RESULTS: The laparoscopic procedure could be completed in 129 patients (94.9%). Seven required conversion to open surgery. The median blood loss was 50 mL (range 20-3000 mL), and the mean operative time was 261 minutes (range 115-570 minutes). There were no perioperative deaths. The mean postoperative hospital stay was 4.1 days. Antegrade ejaculation was preserved in all patients. In the series, 25 patients (18.4%) had pathologic stage IIA disease and received adjuvant chemotherapy consisting of two cycles of cisplatin, etoposide, and bleomycin; none of these patients has relapsed. Eight patients (5.9%) suffered relapses, although L-RPLND had yielded negative lymph nodes in all of them. All eight patients were salvaged with cisplatin-based chemotherapy, with surgery also performed in two patients. All other patients (N = 128, 94.1%) remained relapse free. None of the patients died because of tumor progression. CONCLUSIONS: The L-RPLND has proved to be an excellent staging tool, which should be developed into a less-invasive alternative to primary open RPLND. The oncologic outcome of L-RPLND without adjuvant chemotherapy in pathologic stage II disease is being investigated.

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J Clin Oncol. 2007 Feb 10;25(5):513-6.
Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant.
Einhorn LH, Brames MJ, Juliar B, Williams SD.
Division of Hematology-Oncology, Indiana University School of Medicine, Walther Cancer Institute, Indianapolis, IN, USA. leinhorn@iupui.edu

PURPOSE: To determine long-term survival and potential cure with salvage chemotherapy with paclitaxel plus gemcitabine after progression after both cisplatin combination chemotherapy and subsequent high-dose chemotherapy with tandem transplantation. PATIENTS AND METHODS: One hundred eighty-four patients received salvage high-dose chemotherapy at Indiana University (Indianapolis, IN) from February 1996 to December 2004. After further evidence of progressive disease, 32 patients were subsequently treated with paclitaxel 100 mg/n2 over 1 hour plus gemcitabine 1,000 mg/m2 over 30 minutes, days 1, 8, and 15 every 4 weeks for a maximum of six courses. This is a retrospective review of this patient population. Patients were evaluated for response, duration of response, and survival. Patients were ineligible if they received prior paclitaxel or gemcitabine. RESULTS: Ten (31%) of 32 patients achieved objective response, including four partial remissions (2- to 6-month duration) and six complete responses (CRs). Four of these six CRs (12.5% of total patient population) are continuously disease free (NED) with paclitaxel plus gemcitabine alone (no postchemotherapy surgery) at more than 20, 40, 44, and 57 months from start of paclitaxel plus gemcitabine, respectively. One additional CR is currently NED more than 63 months after paclitaxel plus gemcitabine with two subsequent resections of carcinoma. CONCLUSION: Long-term disease-free survival is possible with paclitaxel plus gemcitabine in this patient population that progressed after high-dose chemotherapy, and had not received prior paclitaxel or gemcitabine.

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Surg Oncol Clin N Am. 2007 Jan;16(1):199-220.
Retroperitoneal lymph node dissection in testicular cancer.
Jacobsen NE, Foster RS, Donohue JP.
Department of Urology, Indiana University, Indiana Cancer Pavilion, 535 N Barnhill Drive, Suite 420, Indianapolis, IN 46202, USA.

With long-term survival in excess of 90% across all stages, testicular cancer has come to represent the model for successful multidisciplinary cancer care. Retroperitoneal lymph node dissection (RPLND) remains an integral component of testis cancer management strategies for both early- and advanced-stage disease. Commensurate with improvements made in clinical staging and in our understanding of the natural history of testis cancer, lymphatic spread, and neuroanatomy, considerable modifications in the technique and template of RPLND have taken place. The morbidity of primary RPLND and postchemotherapy RPLND is low when performed by experienced surgeons. This article reviews the evolution, role, and technique of RPLND in contemporary practice.

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Oncologist. 2007 Jan;12(1):51-61.
Management of recurrent testicular germ cell tumors.
Sonpavde G, Hutson TE, Roth BJ.
US Oncology Research, Houston, Texas, USA. guru.sonpavde@usoncology.com

Although front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still important in a small but significant minority. Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients. New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, have added to the therapeutic armamentarium. Salvage surgical resection has an important role in selected patients. Cisplatin-refractory patients have a poor prognosis with current therapy, and novel chemotherapeutic and biologic agents need to be discovered for such patients.

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Ned Tijdschr Geneeskd. 2006 Dec 2;150(48):2637-42.
[Treatment of testicular cancer clinical stage I: watchful waiting, radiotherapy, chemotherapy or surgical intervention]
[Article in Dutch]
Spermon JR, Witjes JA.
Universitair Medisch Centrum St Radboud, afd. Urologie, Postbus 9101, 6500 HB Nijmegen.

Micrometastasis in the retroperitoneal lymph nodes is seen in 20% of patients with a seminoma in clinical stage I and in 30% of patients with a nonseminoma in clinical stage I. It is not possible to detect micrometastases. Nearly all patients recover from the illness irrespective of the treatment choice. This is based on the patient's wish, the doctor's preference, local expertise and risk factors for dissemination. In the case of a seminoma, treatment consists of regular checks ('watchful waiting'), radiotherapy or chemotherapy. In the case of a non-seminoma in clinical stage I without vascular impingement the risk of micrometastases in the retroperitoneal nodes is 15%. Standard treatment consists of watchful waiting. The options 'retroperitoneal lymph node dissection with, in the case of positive nodes, chemotherapy' and 'primary chemotherapy' result in more excessive treatment, but less uncertainty in patients. In the case of a non-seminoma in clinical stage I with vascular impingement, the risk of micrometastases is 50%. Standard treatment in this case consists of watchful waiting or retroperitoneal lymph node dissection with chemotherapy, if necessary, in case of positive lymph nodes. Another option is primary chemotherapy.

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J Clin Oncol. 2006 Dec 1;24(34):5403-7.
Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors.
Bedano PM, Brames MJ, Williams SD, Juliar BE, Einhorn LH.
Division of Hematology-Oncology and Biostatistics, Indiana University Medical Center and Walther Cancer Institute, Indianapolis, IN, USA. pabedano@iupui.edu

PURPOSE: Initial cisplatin (CIS) combination chemotherapy will cure 70% of patients with disseminated testicular cancer. This phase II clinical trial evaluated the combination of CIS plus epirubicin (CIS-EPI) in patients with metastatic germ cell tumors (GCT) not amenable to cure with standard salvage therapy. PATIENTS AND METHODS: Between March 2001 and August 2005, 30 patients with GCT, who had received at least one previous CIS-based regimen, were enrolled. All patients were males, with median age 36 (range, 24 to 45 years). Twenty-one patients (70%) had experienced late relapses (> 2 years). Patients received EPI 90 mg/m2 on day 1 and CIS 20 mg/m2 on days 1 to 5 every 3 weeks for maximum of four cycles. RESULTS: Nineteen (63%) of 30 patients received all four cycles. Toxicity was primarily hematologic: grade 3/4 neutropenia, four patients (one neutropenic fever); two patients had grade 3 thrombocytopenia, and five patients had grade 3/4 anemia. Nonhematologic toxicity was grade 3 acute renal failure in two patients; grade 3 electrolyte wasting in two patients; grade 3 nausea/vomiting in eight patients; grade 3 elevation of aminotransferases in one patient; and grade 3 diarrhea in one patient. There were no occurrences of severe mucositis, cardiotoxicity, or treatment-related deaths. Nine patients achieved a complete remission; seven of these patients remain without evidence of disease at 25+, 27+, 29+, 44+, 45+, 46+, and 48+ months. One patient remains alive with stable pulmonary nodules at 28+ months. CONCLUSION: CIS-EPI is an active regimen in metastatic GCT, with an acceptable toxicity profile. This regimen offers potential for long-term disease-free survival in this population.

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J Urol. 2006 Nov;176(5):1996-9; discussion 1999.
Adjunctive nephrectomy at post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer.
Stephenson AJ, Tal R, Sheinfeld J.
Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

PURPOSE: Patients with metastatic testicular cancer with residual masses encasing the renal hilum or kidney after platin based chemotherapy may require adjunctive nephrectomy to achieve complete resection at post-chemotherapy retroperitoneal lymph node dissection. We reviewed our experience with adjunctive nephrectomy to assess the impact on cancer control and renal function. MATERIALS AND METHODS: Of 647 post-chemotherapy retroperitoneal lymph node dissection procedures performed at our institution since 1989 adjunctive nephrectomy has been performed in 32 patients (5%). Patient information was obtained from a prospective database. Median followup was 31 months. RESULTS: Of the adjunctive nephrectomy procedures 17 (53%) were performed in high risk settings such as post-salvage chemotherapy, desperation retroperitoneal lymph node dissection, late relapse and reoperative retroperitoneal lymph node dissection. Disease was present in the adjunctive nephrectomy specimen in 21 patients (66%). Following post-chemotherapy retroperitoneal lymph node dissection 7 patients had disease relapse and 5-year disease-free survival was 66%. No case of relapse required substitution for cisplatin due to compromised renal function. Progression to chronic renal insufficiency occurred in 3 patients, 1 of whom required hemodialysis. The calculated creatinine clearance after adjunctive nephrectomy was more than 30% below the age specific norm in 14 patients (50%) and median patient age was 40 years. CONCLUSIONS: Adjunctive nephrectomy at post-chemotherapy retroperitoneal lymph node dissection is most frequently performed in patients with high risk features to ensure the completeness of resection. When indicated, adjunctive nephrectomy should be performed because residual cancer is frequently present and long-term cancer control can be achieved in 66% of patients. Although adjunctive nephrectomy did not interfere with subsequent chemotherapy, the renal reserve in these patients was substantially reduced in 50%, emphasizing the importance of preventative measures to preserve long-term renal function.

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J Urol. 2006 Nov;176(5):1921-6.
Integrating metastasectomy in the management of advanced urological malignancies-where are we in 2005?
Rasco DW, Assikis V, Marshall F.
Medicine Department, Emory University Medical School, Atlanta, Georgia 30322, USA.

PURPOSE: In the past patients with metastatic cancer were considered incurable and they were not candidates for surgical management of metastases. However, experience with testicular cancer has shown that metastasectomy can often be the final, critical step in achieving disease-free status. We summarized the most current data on metastasectomy for advanced urological malignancies. MATERIALS AND METHODS: We performed an extensive review of the literature from 1990 to the present using MEDLINE. Only original reports were included with an emphasis on specific malignancies and specific sites of metastasis. RESULTS: There is increasing evidence that patients with metastatic renal cell carcinoma and bladder carcinoma can be cured by surgical resection of metastases, usually combined with systemic therapy. The ideal patient has responded to systemic therapy and has few metastatic sites. CONCLUSIONS: Metastasectomy should frequently be done in patients with advanced testicular cancer and it should increasingly be considered in patients with metastatic renal cell carcinoma or bladder carcinoma. This technique may be used for cure and palliation. Specific patient factors determine the likelihood and degree of potential benefit.

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J Endourol. 2006 Sep;20(9):627-31.
Laparoscopic and open retroperitoneal lymph-node dissection for clinical stage I nonseminomatous germ-cell testis tumors.
Abdel-Aziz KF, Anderson JK, Svatek R, Margulis V, Sagalowsky AI, Cadeddu JA.
Department of Urology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.

BACKGROUND AND PURPOSE: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) has been reported as efficacious for staging of the retroperitoneum in patients with stage I nonseminomatous germ-cell testis tumors (NSGCT). However, reports are limited to a few centers, and this procedure has yet to be widely accepted as an alternative to open retroperitoneal lymph node dissection (O-RPLND). Thus, we compared our contemporary open and laparoscopic experience with RPLND. PATIENTS AND METHODS: A retrospective chart review identified 28 patients who underwent either open (N = 6) or laparoscopic (N = 22) RPLND for clinical stage I NSGCT since 2000. Each patient received the appropriate modified template dissection. Perioperative demographic data, histologic nodal status, and recurrence data were evaluated. The mean follow-up was similar in the two groups. RESULTS: The mean operative time was not significantly different (313 minutes for L-RPLND v 284 minutes for O-RPLND). However, L-RPLND did have a significantly shorter hospitalization (1.2 v 8.5 days). Significantly more lymph nodes were removed with O-LPLND than with L-RPLND (mean 33 v 17). There was a single recurrence outside the modified template after both L-RPLND and O-RPLND and one within-the-template recurrence in the O-RPLND group. CONCLUSIONS: The L-RPLND is associated with less blood loss and a shorter hospital stay than O-RPLND, whereas the lymph-node yield of O-RPLND is greater. However, during the critical early follow-up period, the oncologic effectiveness and morbidity of L-RPLND for clinical stage I NSGCT appears similar to that of O-RPLND.
  
Previous Testicular Cancer Research:
2002-2006   
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