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Purpose To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse. Methods Retrospective study including data from 2,483 clinical stage I (CSI) patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active surveillance, with the majority treated between 1998 and 2010. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded. Results Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months) and 14 months (range, 2-84 months) for lymphovascular invasion–positive CSI nonseminoma, lymphovascular invasion–negative CSI nonseminoma and CSI seminoma. Most relapses were observed within the first 2 years/3 years after orchiectomy for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of lymphovascular invasion–negative and 41%/61% of lymphovascular invasion–positive patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses exhibited International Germ Cell Collaborative Group good-risk features. Three patients with CSI nonseminoma died of disease (0.3%). One patient with CSI seminoma and two patients with CSI nonseminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy. Five-year disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%). Conclusion Active surveillance for CSI testis cancer leads to excellent outcomes. The vast majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen. These data may inform further refinement of rationally designed surveillance schedules.

Purpose Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P < .001), < 10% of viable malignant cells (P = .001), and a good International Germ Cell Consensus Classification (IGCCC) group (P = .01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P < .001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P < .001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P < .001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P < .001) and OS (P = .02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

PURPOSE: To assess the role of high-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. PATIENTS AND METHODS: From August 1992 to April 1998, 65 patients with testicular cancer were treated with high-dose carboplatin and etoposide followed by peripheral-blood stem-cell transplantation or autologous bone marrow transplantation rescue as initial salvage chemotherapy at Indiana University. An identical course was given after hematopoietic reconstitution. Postchemotherapy resection of residual disease was performed in selected patients with incomplete radiographic response associated with normalization of markers. The median follow-up was 39 months (range, 16 to 91 months). RESULTS: Thirty-seven (57%) of the 65 patients are continuously disease-free. Three additional patients are disease-free with subsequent surgery. High-dose chemotherapy was associated with significant morbidity but no treatment-related mortality. CONCLUSION: High-dose chemotherapy as initial salvage chemotherapy achieved impressive long-term survival with acceptable toxicity in patients with relapsed testicular cancer.

Two cycles of bleomycin, etoposide, and cisplatin (BEP) were evaluated as adjuvant chemotherapy for patients with pathological stage II non-seminomatous germ cell tumours. Between 1985 and 1995, 86 patients with pathological stage II non-seminomatous testicular cancer were treated with two cycles of BEP. At retroperitoneal lymph node dissection (RPLND) 49 patients (57%) had pathological stage II(A) (microscopic nodal metastases) and 37 (43%) had stage II(B) (gross nodal metastases). After RPLND, the patients received bleomycin, 30 units weekly for 8 weeks, etoposide (100 mg/m(2)) and cisplatin (20 mg/m(2)) each for 5 days every 28 days for two cycles as adjuvant chemotherapy. 4 patients were lost to follow-up. 10 patients (12%) developed granulocytopenic fever during their chemotherapy. Of the 82 evaluable patients all remained with no evidence of disease except for a single patient with a cervical nodal relapse of teratoma. This was resected and he remains disease free. Median follow-up has been 85 months (range: 42-173 months). In patients with fully resected stage II non-seminomatous germ cell tumour, two cycles of BEP were almost universally effective in preventing relapse.

Background. The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. Methods. Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. Results. A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P

Treatment of recurrent germ cell tumors is a complex undertaking. There are a number of clinical scenarios that can mimic relapse and, as such, a great deal of experience with management of germ cell tumors is required to recognize these rare but important situations that simulate recurrence. If recurrence is proven, standard chemotherapy with cisplatin, ifosfamide, and etoposide can result in approximately 30% of patients being long-term, disease-free survivors. Emerging technologies, e.g., high-dose chemotherapy and new drugs, may augment our current ability to salvage this patient population. Desperation surgery offers an additional opportunity for selected patients with localized chemotherapy-resistant relapse or those patients with late relapse of germ cell tumor. Semin. Surg. Oncol. 17:268–274, 1999. © 1999 Wiley-Liss, Inc.

PURPOSE This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin. PATIENTS AND METHODS From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles. RESULTS Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free. CONCLUSION VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.

This phase II trial investigated the activity and toxicity of CODE (cisplatin, vincristine, doxorubicin, etoposide) chemotherapy with the addition of granulocyte colony-stimulating factor (G-CSF) in patients who had chemotherapy-naive, advanced, or metastatic non-small-cell lung cancer. Treatment consisted of cisplatin, 25 mg/m2, administered weeks 1 through 9; vincristine, 1 mg/m2, weeks 1, 2, 4, 6, and 8; doxorubicin, 40 mg/m2, weeks 1, 3, 5, 7, and 9; and etoposide, 80 mg/m2 intravenously day 1 and 160 mg/m2 orally, days 2 and 3 on weeks 1, 3, 5, 7, and 9. Granulocyte colony-stimulating factor, 5 microg/kg, was administered subcutaneously on all days that patients were not receiving chemotherapy. From April 1992 through April 1993, 42 patients were entered on study. The principal toxicities were hematologic. Grade 3-4 anemia was seen in 21 patients. Grade 3-4 thrombocytopenia was seen in 9 patients. Grade 3-4 neutropenia occurred in 29 patients. Eight patients experienced a neutropenic febrile episode requiring antibiotics. Nonhematologic toxicities included weight loss and fatigue. Responses were seen in 10 of 42 patients, for an overall response rate of 24% (95% confidence interval, 12%-39%) and a median survival of 7.1 months. The CODE chemotherapy regimen has activity similar to other previously described cisplatin-based regimens, with a significant amount of both hematologic and nonhematologic toxicity. Its continued use in patients who have previously untreated non-small-cell lung cancer cannot be recommended, based on the results of this study.

PURPOSE To determine the therapeutic results in advanced germ cell tumor (GCT) patients with initial human chorionic gonadotropin (hCG) elevation greater than 50,000 mIU/mL and to document the levels of hCG decline and subsequent plateau and outcome of this patient population. PATIENTS AND METHODS We conducted a retrospective review of 41 patients who presented to Indiana University (IU) with hCG levels greater than 50,000 mIU/mL between December 1976 and August 1996. All patients had received cisplatin-containing regimens and were monitored with serial hCG levels. RESULTS Twenty-two of 41 (53.7%) patients continuously show no evidence of disease (NED) and eight additional patients (19.5%) are currently NED with salvage therapy. Only two of 41 patients had a normal hCG level at the start of the fourth and final course of cisplatin combination chemotherapy. Eight additional patients showed normalized hCG levels 1 month later. Seven of these 10 are continuously NED and three are currently NED with salvage therapy. Thirty-one patients had an abnormal hCG greater than 1 month after they completed primary chemotherapy; 15 of these patients (48%) are continuously NED despite no further therapy and five additional patients (16%) are currently NED with salvage therapy. Overall, there was an initial rapid decline in hCG followed by a plateau after the first two courses of therapy. CONCLUSION Less than 10% of patients who present with hCG levels greater than 50,000 mIU/mL will have a normal hCG at the institution of the fourth and final course of chemotherapy. However, 22 of 41 (53.7%) are continuously NED despite no further therapy. We feel that the optimal strategy for such patients is monthly observation with initiation of salvage therapy if and when there is serologic progression.

PURPOSE To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS AND METHODS A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed. RESULTS Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP. CONCLUSION BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.

To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade non-Hodgkin's lymphoma who were eligible for autologous transplantation were randomized to receive r-metHuSCF (5, 10, 15, or 20 μg/kg/d) plus Filgrastim (10 μg/kg/d) or Filgrastim (10 μg/kg/d) alone to mobilize peripheral blood progenitor cells. Subcutaneous administration of r-metHuSCF was well tolerated in conjunction with a multi-agent pre-medication regimen; local injection site reactions were the most commonly seen adverse event. The total mononuclear cell count, CD34+ cell content, granulocyte-macrophage colony-forming cells (GM-CFC), and burst-forming units-erythroid (BFU-E) per kilogram in the apheresis product was similar when all patients were analyzed by treatment cohort and mobilization regimen (Filgrastim or r-metHuSCF in combination with Filgrastim); however, when prior chemotherapy was taken into account in a supplementary analysis, clinically important differences were observed. Extensive prior therapy was defined as the amount of exposure to specific stem cell toxic chemotherapeutic agents that patients received. These agents include procarbazine, nitrogen mustard, melphalan, nitrosoureas (≥2 cycles of any of these drugs) or greater than 7.5 g of cytosine arabinoside. In these patients, there was an increased number of CD34+ cells (1.76 v 0.28 × 106/kg), GM-CFC (20.5 v 5.0 × 104/kg), and BFU-E (36.9 v 8.9 × 104/kg) in patients receiving r-metHuSCF and Filgrastim (N = 18) compared with Filgrastim alone (N = 5). These patients also had a decreased time to an untransfused platelet count of 20 × 109/L that was 10.5 days shorter in the patients who received r-metHuSCF and Filgrastim (12.5 v 23 days). These differences were not found to be statistically significant, possibly because of small size, but are clinically important.

BACKGROUND The purpose of this study was to evaluate the use of two cycles of high dose chemotherapy with autologous bone marrow transplantation (ABMT) in the treatment of patients having a first relapse of testicular germ cell cancer. METHODS Twenty-five patients whose disease had relapsed after 1 platinum-based regimen received 1-2 cycles of conventional dose salvage therapy, followed by a planned 2 consecutive cycles of carboplatin 2100 mg/m2 and etoposide 2250 mg/m2 with ABMT. Patients were required to have testicular germ cell cancer, adequate organ function, and performance status. The median patient age was 32 years; 3 cisplatin refractory. RESULTS Conventional dose salvage therapy consisted of vinblastine, ifosfamide, and cisplatin (for 16 patients); etoposide, cisplatin, and ifosfamide (for 3 patients); cisplatin, vinblastine, and bleomycin (for 2 patients); or none (for 4 patients). Twenty-five patients received high dose therapy; of these, 19 (76%) received two cycles. The median time to an absolute neutrophil count of 500 was 12 days (range, 8-20 days) for the first cycle and and 11 days (range, 8-18 days) for the second. The median time to a platelet count of 20,000/μL, independent of transfusions, was 15 days (range, 8-60 days) for the first cycle and 14 days (range, 8-22 days) for the second. Extramyeloid toxicities were as follows: Grade 3-4 stomatitis in 17 of 25 patients, Grade 3-4 nausea/emesis in 12 of 25 patients, and Grade 3 ototoxicity in 3 of 25 patients. At the completion of therapy, nine patients were in complete remission, six had only teratoma found at resection, one had carcinoma resected, six were in partial remission, two had stable disease, and one had progressive disease. With a median follow-up period of 26 months (range, 14-36 months), 13 of 25 patients (52%) had been continuously progression free at last follow-up, 11 of 25 (44%) progressed, and 1 patient died in treatment. CONCLUSIONS Salvage treatment incorporating brief conventional dose therapy followed by two cycles of high dose therapy resulted in prolonged disease free survival in a proportion of patients with relapsed testicular germ cell cancer. Cancer 1997; 79:1605-10. © 1997 American Cancer Society

Study objectives The purpose of this study is to determine whether co-administration of granulocyte colony stimulating factor (G-CSF) and bleomycin results in enhanced pulmonary toxicity compared with bleomycin alone. Design A retrospective analysis comparing two groups of patients with advanced germ cell tumors receiving combination chemotherapy that includes bleomycin with or without G-CSF. Setting Indiana University Medical Center. Patients Group A consisted of 29 patients with advanced-stage germ cell tumors who were treated with combination chemotherapy that included bleomycin. All patients received concurrent prophylactic G-CSF. Group B consisted of 57 patients with advanced-stage germ cell tumors who were treated on a phase 3 study comparing standard BEP (bleomycin, etoposide, cisplatin) to BEP with twice the cisplatin dose. None of these patients received growth factor. Results Of the 29 patients who received concurrent chemotherapy and G-CSF, ten (34%; 95% confidence interval [CI], 17.9 to 54.3%) were believed to have clinically significant bleomycin toxicity. Of the 57 patients who did not receive growth factor, 19 (33%; 95% CI, 21.4 to 47.1%) had bleomycin-related toxicity. There was no difference in the incidence of pulmonary toxicity between the groups (p=1.00 by Fisher's Exact Test). Conclusions There is no increase in pulmonary toxicity with co-administration of G-CSF and bleomycin compared to bleomycin alone in patients with advanced germ cell tumors.

In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.

Craig R. Nichols, Virginia Mason Medical Center, Seattle, WA Bruce Roth, Washington University School of Medicine, St Louis, MO Peter Albers, University Hospital Heinrich-Heine, University of Dusseldorf, Dusseldorf, Germany Lawrence H. Einhorn and Richard Foster, Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN Siamak Daneshmand, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA Michael Jewett and Padraig Warde, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Christopher J. Sweeney and Clair Beard, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA Tom Powles, Bart’s Cancer Institute, St Bartholomew’s Hospital, Queen Mary University of London, London, United Kingdom Scott Tyldesley and Alan So, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada Christopher Porter and Semra Olgac, Virginia Mason Medical Center, Seattle, WA Karim Fizazi, Institute Gustave Roussy, University of Paris Sud, Paris, France Brandon Hayes-Lattin, Knight Cancer Institute, Oregon Health and Science University, Portland, OR Peter Grimison, Royal Prince Alfred Hospital, Sydney Cancer Centre, University of Sydney, Sydney, New South Wales, Australia Guy Toner, Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Victoria, Australia Richard Cathomas, Kantonsspital Graubuenden, Chur, Switzerland Carsten Bokemeyer, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany Christian Kollmannsberger, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada

In approximately 25% of patients with testicular germ cell tumor (GCT), the cancer metastasizes to lymph nodes and distant organs. The initial lymphatic drainage site of GCTs is the retroperitoneum. GCTs rarely involve mesenteric lymph nodes. In this study, we report a case of a 32-year-old male patient with GCT and associated mesenteric lymphadenopathy.

In the United States, there are about 8,500 new cases of germ cell tumors in men over 18 years old. Germ cell cancers are the leading cause of cancer in young men, and advances in treatment over the last 40 years have resulted in cure rates exceeding 95 % in centers of excellence and in populations with centralized management of germ cell tumors.

Additional participating institutions include: Siouxland Hematology-Oncology Associates, Sioux City, IA (Donald Wender, MD); Toledo Community Hospital Oncology Program (Rex B. Mowat, MD); Medical College of Georgia, Augusta, GA (Anand P. Jillella MD); Iowa Oncology Research Association CCOP, Des Moines, IA (Robert J. Behrens, MD); Rapid City Regional Hospital, Inc, Rapid City, SD (Richard Charles Tenglin, MD); Columbus CCOP, Columbus, OH (J. Philip Kuebler, MD, PhD); Michigan Cancer Research Consortium, Ann Arbor, MI (Philip J. Stella, MD); Meritcare Hospital CCOP, Fargo, ND (Preston D. Steen, MD); Geisinger Clinic & Medical Center CCOP, Danville, PA (Albert M. Bernath Jr, MD); Montana Cancer Consortium CCOP, Billings, MT (Benjamin T. Marchello, MD); Sioux Community Cancer Consortium, Sioux Falls, SD (Miroslaw Muzurczak, MD); Lehigh Valley Hospital, Allentown, PA (Suresh Nair, MD); Colorado Cancer Research Program, Denver, CO (Eduardo R. Pajon Jr, MD); Mayo Clinic Arizona, Scottsdale, AZ (Michele Y. Halyard, MD); Medcenter One Health Systems, Bismarck, ND (Edward J. Wos, DO); Carle Cancer Center CCOP, Urbana, IL (Kendrith M. Rowland Jr, MD); Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA (Martin Wiesenfeld, MD); Hematology & Oncology of Dayton, Inc, Dayton, OH (Howard M. Gross, MD); Essentia Duluth CCOP, Duluth, MN (Daniel A. Nikcevich, MD); Altru Health Systems, Grand Forks, ND (Grant Seeger, MD); Grand Rapids Clinical Oncology Program, Grand Rapids, MI (Martin J. Bury, MD); Grand Rapids Clinical Oncology Program, Grand Rapids, MI; St. Vincent Regional Cancer Center CCOP, Green Bay, WI (Anthony J. Jaslowski, MD); Hawaii Minority-Based CCOP (William S. Loui, MD); Heartland Cancer Research CCOP, St. Louis, MO (Alan P. Lyss, MD); Edward Comprehensive Cancer Center, Huntington, WV (Maria Rosalia B. Tri Tirona, MD); Marshfield Clinical Research Foundation, Minocqua, WI (Matthias Weiss, MD); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN (Patrick J. Flynn, MD); Missouri Valley Cancer Consortium, Omaha, NE (Gamini S. Soori, MD); University of New Mexico, Albuquerque, NM (Zoneddy R. Dayao, MD); Northern Indiana Cancer Research Consortium CCOP, South Bend, IN (Robin T. Zon, MD); Cancer Care Associates, Tulsa, OK (Alan M. Keller, MD); Illinois Oncology Research Assn. CCOP, Peoria, IL (John W. Kugler, MD); Columbia River Oncology Program, Portland, OR (Janet C. Ruzich, MD); CentraCare Clinic, St. Cloud, MN (Donald J. Jurgens, MD); Cancer Research for the Ozarks, Springfield, MO (Robert L. Carolla, MD).

PURPOSE To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

Purpose : A Phase II study to evaluate the effect of a five-drug regimen, VP-16, ifosfamide, cisplatin, vinblastine, and bleomycin (VIP/VB) on complete response rate, continuous disease-free survival, and toxicity in patients with advanced germ-cell tumor. Patients and methods : Twenty male patients with a histologic diagnosis of advanced-stage germ-cell cancer, previously untreated with chemotherapy, received the following: etoposide 75 mg/m 2 i.v. days 1-5 ; ifosfamide (with mesna uroprotection) 1.2 g/m 2 i.v. days 1-5 ; cisplatin 20 mg/m 2 i.v. days 1-5 ; vinblastine 0.18 mg/kg i.v. day 1 ; bleomycin 30 units i.v. day I ; filgrastim 5 μg/kg days 7-16. Chemotherapy was given every 3 weeks (bleomycin weekly X 12) for four courses. Results : All patients entered were evaluable for toxicity, response, and survival. Eleven of 20 (55%) achieved complete remissions with chemotherapy alone and an additional 5 (25%) were rendered disease-free with surgical resection of teratoma (3) or viable cancer (2). Two patients relapsed at 4 and 5 months from complete remission (CR). There was one treatment-related death, from bleomycin lung toxicity after thoracotomy. Thirteen patients (65%) are alive and continuously free of disease, with a median follow-up of 20 months and a minimal follow-up of 12 months. Hematologic toxicity was most common, with 16 patients (80%) having grade 3 or 4 leukopenia. Conclusion : VIP/VB appears to be a very active regimen in advanced disseminated germ-cell cancer. Hematological toxicity was severe but manageable.

PURPOSE Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended.

Introduction Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular germ cell tumor is technically difficult and associated with significant morbidity. We postulated that a novel midline extraperitoneal (EP) approach might minimize the morbidity. Technical Considerations We describe a midline extraperitoneal approach in detail. The operative time, estimated blood loss, lymph node yield, return of bowel function, length of stay, and postoperative complications were retrospectively reviewed. From April 2010 to May 2011, 12 consecutive patients underwent EP-RPLND at 2 tertiary centers by a single surgeon, including 5 primary and 7 postchemotherapy RPLNDs. The clinical characteristics and outcomes were compared with those from a matched cohort of transperitoneal-RPLND patients. Results The median follow-up was 173 and 201 days in the EP and transperitoneal groups, respectively. The EP group had a shorter mean operative time of 292 versus 337 minutes (P = .02) and lower estimated blood loss of 305 versus 575 mL (P = .05). More lymph nodes were retrieved in the EP group (44 vs 27 nodes, P = .0006). Finally, an earlier return of bowel function (1.7 vs 2.9 days, P = .0001) and a shorter median length of stay (3.3 vs 5.3 days, P = .0001) was seen in the EP group. Conclusion EP-RPLND can be performed safely without prolonged operative times or compromised lymph node retrieval, even in the postchemotherapy setting, and is associated with a faster return of bowel function and shortened length of stay.

Some controversy still exists regarding the management of testis cancer following chemotherapy for disseminated disease.To review the available literature concerning the management of postchemotherapy testis cancer.A Medline search was conducted to identify original and review articles, as well as guidelines addressing the management of testis cancer following first-line chemotherapy. Keywords included germ cell tumor, testis cancer, retroperitoneal lymph node dissection, and chemotherapy. The most relevant articles were critically reviewed with the consensus of all the collaborative authors, who have expertise in the management of germ cell tumors (GCTs).Approximately one-third of patients who undergo chemotherapy for metastatic GCTs have residual retroperitoneal disease. All patients with residual masses ≥1cm after chemotherapy for nonseminomatous GCTs should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) because of the risk of mature teratoma in 40-45% of cases and of viable GCT in 10-15% of cases. Patients who obtain a complete serologic remission and radiographic residual1 cm after chemotherapy have a 6-9% risk of relapse. Patients with a completely resected teratoma in only the PC-RPLND specimen have a90% chance of cure, while patients with viable GCTs should be considered for additional therapy, depending on the percentage of viable tumor. In patients with disseminated seminoma, postchemotherapy masses3cm may be safely observed, while patients with masses3 cm should be evaluated with positron emission tomography (PET)/computed tomography 2 mo after completion of chemotherapy, with very selective administration of PC-RPLND. Late relapse occurring2 yr after chemotherapy is rare, and surgery remains the mainstay of therapy in cases of resectable masses independent of tumor markers. There is still controversy on whether high-dose chemotherapy confers a survival benefit compared with conventional-dose chemotherapy in the salvage setting. Surgery should always be considered for resectable masses following salvage therapies or in chemoresistant disease to maximize chance of cure.Patients with advanced GCTs can achieve long-term disease-free survival when chemotherapy is combined with expert and judicious resection of residual disease. PC-RPLND is recommended for residual masses1cm identified on postchemotherapy imaging in nonseminomatous GCT and possibly for PET-positive residual disease ≥3cm in treated seminomas.

Italian]. Minerva Ginecol 42:515-518, 1990 6. Jacoby VL, Autry A, Jacobson G, et al: Nationwide use of laparoscopic hysterectomy compared with abdominal and vaginal approaches. Obstet Gynecol 114:1041-1048, 2009 7. Seamon LG, Fowler JM, Richardson DL, et al: A detailed analysis of the learning curve: Robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial cancer. Gynecol Oncol 114:162-167, 2009 8. Leitao MM Jr, Gardner GJ, Briscoe G, et al: Comparison of robotically assisted and standard laparoscopic procedures in patients with endometrial cancer. Presented at the Society of Gynecologic Oncologists 42nd Annual Meeting on Women’s Cancer 2011, Orlando, FL, March 6-9, 2011 (abstr 296) 9. Jonsdottir GM, Jorgensen S, Cohen SL, et al: Increasing minimally invasive hysterectomy: Effect on cost and complications. Obstet Gynecol 117:1142-1149, 2011 10. Wikipedia: IBM 5100. http://en.wikipedia.org/wiki/IBM_5100 11. Apple: iPad. http://www.apple.com/ipad/

PURPOSE We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.

BACKGROUND Patients with relapsed germ cell cancer (GCT) have a poor prognosis when treated solely with conventional chemotherapy; high dose chemotherapy with autologous bone marrow rescue (ABMR) has shown curative potential in patients with relapsed and refractory GCT. This protocol was designed to incorporate high dose therapy with initial salvage therapy. METHODS Twenty-three patients in the first relapse of GCT received two cycles of conventional dose cisplatin-based therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin, vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS Eighteen of 23 patients completed protocol therapy including high dose therapy. Five of 23 did not undergo high dose therapy due to: insurance refusal (1); patient refusal (1); active infection (1); central nervous system metastasis (1); death on induction therapy (1). Response to two courses of conventional dose induction therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue with high dose therapy are alive and progression free after conventional salvage therapy and surgery with at least 24 months of follow-up. Outcome after high dose therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR after receiving two cycles of conventional dose therapy were converted to CR using high dose therapy. There was only one treatment-related death in this cohort, a septic death during VeIP induction therapy. There were no transplant related deaths. Of those patients completing high dose therapy, 7 of 18 (39%) survived, progression free with a median follow-up of 26 months, 2 of 18 are alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS Conventional dose induction therapy followed by consolidation with high dose therapy and ABMR is well tolerated and provides prolonged disease-free survival in some patients with chemosensitive relapsed germ cell cancer.

PURPOSE This multicenter cooperative group phase I/II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 micrograms subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. RESULTS Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. CONCLUSION This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VACI therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.

An 18-year-old male with Klinefelter's syndrome presented with a mature teratoma of the mediastinum. He was treated with de-bulking surgery and brief cisplatin-based chemotherapy. Ten years later, he presented with paraplegia and was found to have an isolated epidural mass. The mass was composed of mature histiocytoid cells reminiscent of those seen in malignant histio-cytosis. There was no evidence of medullary dissemination and there was no evidence of recurrence of the germ cell tumor. He received local radiation therapy and a single course of leukemic induction. He remains well 4 years later. This case represents a localized variant of the diffuse histiocytic malignancies associated with malignant mediastinal germ cell tumors. © 1994 Wiley-Liss, Inc.

Advanced stage nonseminomatous testis cancer is commonly treated with chemotherapy and surgical resection. Patients with retroperitoneal residual masses >1cm following induction chemotherapy with normalized tumor markers should undergo a post-chemotherapy retroperitoneal lymph node dissection. Post chemotherapy retroperitoneal residual mass less than 1 cm with normal markers may be considered as complete response, although the possibility of residual teratoma and viable germ cell tumor are not definitively ruled out. Excellent long term disease free survival following surveillance may justify this option as the treatment of choice in this cohort of patients.

Background. Patients with mediastinal germ cell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy. It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing non-germ cell (hematopoietic) differentiation. Methods. To assess this hypothesis, histologic material from six patients with MGCTs associated with leukemia was examined using monoclonal and polyclonal antibodies capable of labeling cells of the different marrow cell lineages. Results. Morphologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients. In three of the four cases, the cells consisted of poorly differentiated blast cells, whereas in the fourth, clusters of erythroblasts were identified. The leukemic cells within the MGCT and in the bone marrow had similar morphology, constant expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers. Three cases expressed p53, a nuclear protein associated with neoplastic transformation in a wide range of malignancies, including testicular cancers, but which rarely is reported in leukemias. Karyotype of the leukemia was assessed in five cases: two showed an i(12p), a cytogenetic marker of GCT not identified in the usual cases of leukemia. Conclusions. The results support the hypothesis that these leukemic conditions originate in the MGCT through a mechanism of differentiation from a yolk sac tumor-derived progenitor cell, with subsequent homing to the marrow.

BACKGROUND Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure. PURPOSE This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin). METHODS We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. RESULTS The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group. CONCLUSIONS We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer.

Background: In this article, we report the evolution of treatment with increased use of active surveillance for stage I disease as well as risk-adapted chemotherapy for disseminated disease and associated outcomes of testicular seminoma in a contemporary population-based cohort. Methods: All patients with histologically confirmed seminoma referred from 1999 to 2008 to the British Columbia Cancer Agency or Providence Cancer Center were retrospectively reviewed. Both institutions manage ∼90% of testicular cancers in their respective area. Results: A total of 649 patients were included. Clinical stage (CS) distribution: CSI/II/III n = 545/87/17. For CSI, there was a progressive and marked decrease in the utilization of prophylactic radiation (RT), and corresponding increase in the use of active surveillance. No deaths related to seminoma were reported in CSI patients. CSII or CSIII patients received RT or International Germ Cell Cancer Collaborative Group (IGCCCG) risk-appropriate chemotherapy with 101 of 104 patients being in long-term remission and 3 patients dying from treatment complications. For the entire seminoma population

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer. J Natl Cancer Inst 2010; 102: 1114-1130

Background With treatment leading to nearly uniform cure in clinical stage I nonseminomatous testicular cancer (CSI-NSGCT), diminishing treatment-related morbidity has become the primary concern. This study examined feasibility and outcome of active surveillance as treatment in an unselected CSI patient population. Materials and methods All patients with CSI-NSGCT referred from 1998 to 2007 to the British Columbia Cancer Agency and the Oregon Testis Cancer Program were retrospectively reviewed. A total of 233 patients were identified, of which 223 chose active surveillance. Results Vascular invasion (VI) was absent, present and unknown in 66%, 27% and 7% of cases, respectively. Overall, 49% of patients had embryonal predominant disease. Fifty-nine patients (26%) relapsed, all but one with good prognosis disease. VI was present in 30 relapsed patients. Most patients relapsed within 2 years (88%). Only 7 of 223 patients (3%) relapsed beyond 2 years. All relapses were in long-term remission following chemotherapy with or without retroperitoneal lymph node dissection (RPLND). Only 17 of 223 patients (8%) required postorchiectomy surgery. Disease-specific survival is 100% after a median follow-up of 52 months (3–136). No patient has required second-line chemotherapy. Conclusions Active surveillance for all CSI-NSGCT patients is associated with excellent outcomes comparable with the best results reported with primary RPLND or adjuvant chemotherapy. Nearly 75% of patients are spared any therapy after orchiectomy.

Testicular cancer is the most common solid tumor among males in the 20–39 year-old age range. Moreover, testicular cancer has unique biological associations, clinical features, and psychosocial impacts that establish this tumor as a prototypic malignancy of young adults. The biology of testicular germ cell tumors after puberty is distinctive. Epidemiologic patterns of testicular cancer suggest etiologic factors that may be congenital, racial, and geographic. The clinical management of a cancer common among young adults, but rare among adults in general, requires expertise so as not to jeopardize the high rates of survivorship associated with modern therapy. The concurrent but separate development of staging, prognostic systems and treatment recommendations, between the fields of pediatric and adult oncology, highlight the need for increased integration and cooperation across these subspecialties. And the high rate of survival, combined with the need for long term monitoring for relapse or late effects, demonstrates the challenge of delivering longitudinal care in this mobile and active young adult population.

This article presents a review of the spectrum of extragonadal germ cell tumors, a fascinating group of rare and biologically diverse tumors. Although like testicular germ cell tumors, these tumors are chemotherapeutically responsive, the overall prognosis is not as good. Pediatric germ cell tumors share many of the biologic characteristics of the adult tumors but are more likely to be benign. An unusual aspect of mediastinal germ cell tumors, in particular, is their association with nontreatment-related hematologic malignancies.

Mediastinal yolk sac tumor (endodermal sinus tumor) is an extremely rare extragonadal germ cell neoplasm that has been associated with a grave prognosis. Twenty-one male patients with mediastinal yolk sac tumor received treatment at Indiana University between 1976 and 1988. Fourteen were seen after initial diagnosis, and their disease was treated with cisplatin-based chemotherapy in association with complete surgical resection if possible. Five are currently alive and disease free (36%). Seven were referred for salvage chemotherapy after relapse of their disease. Despite aggressive chemotherapy, these patients all died; they had a median survival time of 6 months. Our experience suggests that an aggressive combined modality approach with cisplatin-based chemotherapy followed by surgical resection of residual disease is the optimal management of this tumor. New regimens need to be explored for relapse of the disease after initial chemotherapy.