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Objectives: Mediastinal germ cell tumors are rare and few large-scale studies on mediastinal germ cell tumors are reported. We aimed to investigate the clinical characteristics and survival outcomes of patients with mediastinum germ cell tumors in Japan., Methods: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with mediastinal germ cell tumors in 2012-2013. The datasets were registered from 80 institutions., Results: The selection criteria were met by 123 patients, the majority of whom were male. The median age at diagnosis was 39 years (range 25-89 years) and the most common age groups at diagnosis was 30-39 years, followed by 40-49 years and ≥ 50 years. The histology of non-seminoma (55.3%) was slightly more frequent than that of seminoma (44.7%). The most common histological subtype in non-seminoma was yolk sac tumor, followed by mixed germ cell tumor. The 5-year survival of seminoma and non-seminoma were 96.4% and 57.3%, respectively (p < 0.001). Non-seminomatous mediastinal germ cell tumors, malignant teratomas, mixed germ cell tumors, and yolk sac tumors had comparable survival rates, while those with choriocarcinoma showed the worst prognosis., Conclusions: This is the first report showing the clinical characteristics and survival outcomes of mediastinal germ cell tumors in Japan using a real-world large cohort database., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients., Methods: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR)., Results: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p  ≤  0.001), respectively., Conclusions: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification., (© 2021. The Author(s).)

Purpose: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium., Materials and Methods: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients., Results: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH., Conclusion: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor., Competing Interests: Jörg BeyerHonoraria: Roche, Janssen Oncology, AstraZeneca, Astellas Pharma, Bayer, Ipsen Gedske DaugaardConsulting or Advisory Role: Sanofi/Aventis, Astellas Pharma, Bayer, MSD Oncology, Bristol-Myers Squibb/PfizerTravel, Accommodations, Expenses: Astellas Pharma Darren R. FeldmanResearch Funding: Novartis, Seattle Genetics, Decibel Therapeutics, Astellas PharmaOther Relationship: UpToDate Alexey TryakinConsulting or Advisory Role: BioCad, Roche/Genentech, Bristol-Myers Squibb, Eisai, Merck Sharp & DohmeSpeakers' Bureau: Bayer Health, BioCad, Lilly, Merck Serono, Sanofi, Amgen, Bristol-Myers Squibb, Eisai, Merck Sharp & DohmeTravel, Accommodations, Expenses: Novartis, BioCad, Bayer, Veropharm, Sanofi Olof StahlHonoraria: Bayer Enrique Gonzalez-BillalabeitiaTravel, Accommodations, Expenses: Bristol-Myers Squibb, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi, Roche Ugo De GiorgiConsulting or Advisory Role: Pfizer, Janssen, Astellas Pharma, Sanofi, Bristol-Myers Squibb, Bayer, Ipsen, Merck, MSD, PharmaMar, NovartisResearch Funding: Sanofi, AstraZeneca, RocheTravel, Accommodations, Expenses: Bristol-Myers Squibb, Ipsen, Janssen, Pfizer, Roche Stephane CulineConsulting or Advisory Role: Bayer, Janssen, Astellas PharmaSpeakers' Bureau: Takeda, JanssenResearch Funding: Astellas PharmaTravel, Accommodations, Expenses: Ipsen, Janssen Ronald De WitHonoraria: Sanofi, Merck Sharp & DohmeConsulting or Advisory Role: Sanofi, Merck Sharp & Dohme, Janssen, Bayer, Astellas PharmaResearch Funding: Sanofi, BayerTravel, Accommodations, Expenses: Bayer Aaron HansenConsulting or Advisory Role: Merck, GlaxoSmithKline, Bristol-Myers Squibb, EisaiResearch Funding: Karyopharm Therapeutics, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Janssen, AstraZeneca/MedImmune, Astellas Pharma, Macrogenics Marko BebekHonoraria: Roche, Novartis, Janssen Oncology, Sanofi, Sandoz, Astellas PharmaResearch Funding: Roche, Astellas PharmaTravel, Accommodations, Expenses: Roche, Astellas Pharma, Sanofi, Janssen, Novartis Angelika TerbuchResearch Funding: Roche, AstraZeneca, MSD, Bristol-Myers Squibb Costantine AlbanyStock and Other Ownership Interests: AdvaxisHonoraria: Sanofi, AstraZeneca, Seattle GeneticsConsulting or Advisory Role: Seattle Genetics, AstraZeneca/MedImmuneSpeakers' Bureau: SanofiResearch Funding: Astex Pharmaceuticals, Merck, Bristol-Myers Squibb, Lilly, BayerTravel, Accommodations, Expenses: Sanofi Marcus HentrichConsulting or Advisory Role: Amgen, Janssen-Cilag, Sanofi, Hexal, Jazz Pharmaceuticals, TakedaSpeakers' Bureau: Amgen, Janssen-Cilag, Sanofi, Takeda, Bristol-Myers Squibb, Gilead SciencesTravel, Accommodations, Expenses: Celgene, Janssen-Cilag, Takeda Jourik A. GietemaResearch Funding: Roche/Genentech, Abbvie, Siemens Robert A. HuddartEmployment: Aspen Parkside HospitalLeadership: Cancer Clinic London limited liability partnershipHonoraria: Janssen OncologyConsulting or Advisory Role: Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Janssen Oncology, Nektar, BayerSpeakers' Bureau: Roche, MSDResearch Funding: Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, JanssenPatents, Royalties, Other Intellectual Property: Royalties for drug discovery from JanssenTravel, Accommodations, Expenses: Janssen Oncology, Roche/Genentech, MSD Oncology, Nektar Anja LorchHonoraria: MSD Oncology, Merck, MSDConsulting or Advisory Role: Bristol-Myers Squibb, Novartis, AstraZeneca, Roche, MSD Oncology, Janssen Oncology, Ipsen, Merck, PfizerTravel, Accommodations, Expenses: Ipsen, AstraZeneca Daniel Y. C. HengConsulting or Advisory Role: Pfizer, Novartis, Bristol-Myers Squibb, Janssen, Astellas Pharma, Ipsen, Eisai, MerckResearch Funding: Pfizer, Novartis, Exelixis, Bristol-Myers Squibb, Ipsen Christopher J. SweeneyStock and Other Ownership Interests: LeuchemixConsulting or Advisory Role: Sanofi, Janssen Biotech, Astellas Pharma, Bayer, Genentech/Roche, AstraZeneca, Pfizer, Amgen, Celgene, LillyResearch Funding: Janssen Biotech, Astellas Pharma, Sanofi, Bayer, Dendreon, PfizerPatents, Royalties, Other Intellectual Property: Leuchemix, Parthenolide, Dimethylaminoparthenolide. Exelixis: Abiraterone plus cabozantinib combination Eric WinquistHonoraria: Merck, Bayer, Eisai, Amgen, RocheResearch Funding: Roche/Genentech, Merck, Pfizer, Eisai, Ayala Pharmaceuticals Peter GrimisonResearch Funding: Tilray, Pfizer, MSD, Gilead Sciences, Boston Biomedical, Tigermed, Halozyme, Specialised Therapeutics, Medimmune, Pfizer, ASLAN Pharmaceuticals, Genentech, Eisai, Five Prime Therapeutics, QED Therapeutics, Janssen-Cilag Andrea NecchiEmployment: BayerStock and Other Ownership Interests: BayerHonoraria: Roche, Merck, AstraZeneca, Janssen, Foundation Medicine, Bristol-Myers SquibbConsulting or Advisory Role: Merck Sharp & Dohme, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, GlaxoSmithKline, FerringResearch Funding: Merck Sharp & Dohme, AstraZeneca, IpsenTravel, Accommodations, Expenses: Roche, Merck Sharp & Dohme, AstraZeneca, Janssen, Rainier TherapeuticsOther Relationship: Bayer Ben TranHonoraria: Astellas Pharma, Janssen-Cilag, Sanofi, Tolmar, Amgen, Bristol-Myers SquibbConsulting or Advisory Role: Amgen, Astellas Pharma, Bayer, Sanofi, Tolmar, Janssen-Cilag, Bristol-Myers Squibb, Ipsen, MSD Oncology, IQvia, Novartis, Pfizer/EMD Serono, AstraZeneca, Roche Molecular DiagnosticsResearch Funding: Astellas Pharma, Janssen-Cilag, Amgen, Pfizer, Genentech, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, IpsenTravel, Accommodations, Expenses: Amgen, Astellas Pharma Axel HeidenreichHonoraria: Amgen, Astellas Pharma, Bayer, Ferring, Ipsen, Janssen-Cilag, Sanofi, TakedaConsulting or Advisory Role: Astellas Pharma, Bayer, Janssen-Cilag, Clovis Oncology, BMS Global, AstraZeneca, MSD OncologySpeakers' Bureau: Amgen, Astellas Pharma, Bayer, Ipsen, Johnson & Johnson, Sanofi, Takeda, PfizerResearch Funding: Astellas Pharma, Bayer, Sanofi, Bristol-Myers Squibb Jonathan ShamashSpeakers' Bureau: Pfizer/EMD Serono Cora N. SternbergConsulting or Advisory Role: Bayer, MSD, Pfizer, Roche, Incyte, AstraZeneca, Merck, Medscape, UroToday, Astellas Pharma, Genzyme, Immunomedics, Foundation Medicine David J. VaughnResearch Funding: Merck Sharp & Dohme, Roche/Genentech, Astellas Pharma Ignacio DuranHonoraria: Bristol-Myers Squibb, Ipsen, Roche/Genentech, Janssen Oncology, MSD Oncology, Astellas Pharma, EUSA PharmaConsulting or Advisory Role: Roche/Genentech, MSD Oncology, Bayer, Bristol-Myers Squibb, Seattle Genetics, Pharmacyclics, Janssen Oncology, Novartis, ImmunomedicsResearch Funding: Roche/Genentech, AstraZeneca Spain, Janssen Oncology, Astellas PharmaTravel, Accommodations, Expenses: Roche/Genentech, AstraZeneca Spain, Ipsen Carsten BokemeyerHonoraria: Merck KGaA, Sanofi, Roche, Bayer, Bristol-Myers Squibb, AstraZeneca, Merck Sharp & DohmeConsulting or Advisory Role: Lilly/ImClone, Merck Serono, Sanofi, Bayer Schering Pharma, Merck Sharp & Dohme, GSO, AOK Health InsuranceResearch Funding: Abbvie, ADC Therapeutics, Agile Therapeutics, Alexion Pharmaceuticals, Amgen, Apellis Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, BerGenBio, Blueprint Medicines, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eisai, Gilead Sciences, Glycotope GmbH, GlaxoSmithKline, Incyte, iOMEDICO, Isofol Medical, Janssen-Cilag, Karyopharm Therapeutics, Lilly, Millennium, MSD, Nektar, Novartis, Rafael Pharmaceuticals, Roche, Springworks Therapeutics, Taiho PharmaceuticalTravel, Accommodations, Expenses: Merck Serono, Sanofi, Pfizer, Bristol-Myers Squibb Anna PatrikidouConsulting or Advisory Role: Basilea Richard CathomasHonoraria: Janssen-Cilag, Astellas Pharma, Bristol-Myers Squibb, Debiopharm GroupConsulting or Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Pfizer, Roche, MSD Oncology, Janssen-Cilag, Bayer, Sanofi, IpsenTravel, Accommodations, Expenses: AstraZeneca Silke GillessenConsulting or Advisory Role: Astellas Pharma, Janssen, Bayer, Orion Pharma GmbH, Tolero Pharmaceuticals, MSD Oncology, Roche, Amgen, PfizerSpeakers' Bureau: Janssen-CilagPatents, Royalties, Other Intellectual Property: Method for biomarker (WO 3752009138392 A1)Travel, Accommodations, Expenses: ProteoMedixOther Relationship: ProteoMediX, Aranda PharmaNo other potential conflicts of interest were reported.

The aim of the present study was to explore and verify the potential mechanism of seminoma progression. Data on 132 RNA‑seq and 156 methylation sites from stage II/III and I seminoma specimens were downloaded from The Cancer Genome Atlas database. An initial filter of |fold‑change| >2 and false discovery rate <0.05 were used to identify differentially expressed genes (DEGs) which were associated with differential methylation site genes; these genes were considered potential candidates for further investigation by survival analysis. Potassium voltage‑gated channel subfamily C member 1 ( KCNC1 ) expression was verified in seminoma human tissues and three seminoma cell lines. The invasive, proliferative and apoptotic abilities of the human testicular tumor Ntera‑2 and normal human testis Hs1.Tes cell lines were assessed following aberrant KCNC1 expression. KCNC1 was identified as a DEG, in which hypermethylation inhibited its expression and it was associated with poor overall survival in patients with seminoma. The present results demonstrated that KCNC1 is negatively correlated with methylation. Due to the abnormal expression of KCNC1 in seminoma cells, it was suggested that KCNC1 could be used as a diagnostic indicator and therapeutic target for the progression of seminoma.

Background: Adjuvant carboplatin reduces relapse risk in clinical stage 1 (CS1) seminoma, though there is a paucity of long-term safety data., Aim: Our objective was to report long-term outcomes of two cycles of adjuvant carboplatin dosed at area under the time-concentration curve (AUC) of 7., Methods and Results: We performed a retrospective analysis on treatment and outcomes of patients with CS1 seminoma who received adjuvant carboplatin from 2000 to 2016 at our centres in the Midland Region, New Zealand. Of 159 patients, median age 39 years, 153 received two cycles of carboplatin: 147 dosed at AUC7 and 6 at AUC6. Six patients had one cycle of carboplatin AUC7. One patient relapsed at 22 months and died of bleomycin pneumonitis 2 months after achieving a complete response with BEP chemotherapy. Neither RTI (present in 21.3%) nor tumor size >4 cm (in 43.3%) was predictive of relapse. Median follow-up was 106 months. At 15 years, outcomes were: relapse-free survival 99.4%, overall survival 91.4%, disease-specific survival 100%, subsequent malignant neoplasm rate 7.6%, and second testicular germ cell tumor rate 3.85%. One patient had persistent grade 1 thrombocytopenia at 46 months., Conclusions: These data add to the body of evidence that two cycles of carboplatin AUC7 is safe and effective adjuvant treatment for CS1 seminoma., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed., Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT., Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality., Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: To characterize the presentation and management of spermatocytic seminoma (SS) compared to classic seminoma in adults utilizing a large cancer registry., Methods: Patients >18 years of age in the National Cancer Database from 2006 to 2016 who underwent orchiectomy for testicular tumors were identified. Demographics, oncologic characteristics, and treatment patterns were compared between patients with SS and classic seminoma., Results: Of 53,481 adults receiving orchiectomy, 29,208 were diagnosed with classic seminoma and 299 (1%) with SS. Compared to patients with classic seminoma, SS patients were older (57 vs 39 years) and more likely to be African-American (odds ratio (OR) 1.8) and insured by Medicare (OR 2.0; all P <.05). SS patients had larger tumors on presentation (3-6 cm: OR 1.8; >6 cm: OR 1.8), but were less likely to have ≥pT2 stage (OR 0.5), regional nodal involvement (Clinical Stage II: OR 0.3), or distant metastatic disease (Clinical Stage III: OR 0.1; all P <.01). For postorchiectomy management, 73.6% of SS patients underwent surveillance while 24.5% had active treatment (retroperitoneal lymph node dissection, chemotherapy, radiation, or a combination). When stratified by year, there was an increasing trend toward surveillance compared to active treatment., Conclusion: SS is a rare germ cell tumor that typically presents as a larger tumor in older patients. Although these tumors are less likely to be characterized by advanced disease compared to classic seminoma, many patients have undergone aggressive postorchiectomy treatment in the past. Importantly, treatment trends have shifted toward surveillance in recent years with adjuvant therapy limited primarily to higher stage tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis., Competing Interests: None

Background: Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. We aimed to assess the prognostic value of previously suggested biomarkers, related to proliferation (MIB-1 and TEX19) and to immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a surveillance cohort of stage I testicular germ cell tumor patients., Methods: A total of 70 patients were included. Survival analyses were performed, including Cox regression models., Results: Patients with vascular invasion and elevated human chorionic gonadotropin levels showed significantly poorer relapse-free survival in multivariable analysis (hazard ratio = 2.820, 95% confidence interval 1.257-6.328; hazard ratio = 3.025, 95% confidence interval 1.345-6.808). Patients with no vascular invasion but with MIB-1 staining in > 50% tumor cells showed significantly shorter relapse-free survival (p = 0.042). TEX19 nuclear immunoexpression was confirmed in spermatogonial cells, and weak cytoplasmic immunoexpression was depicted in 15/70 tumors, not significantly impacting survival. CXCL12 immunoexpression in tumor cells did not associate with relapse, but non-seminoma patients exhibiting vascular invasion and CXCL12-positive stromal/inflammatory cells showed significantly improved relapse-free survival (p = 0.015). Exclusively nuclear immunoexpression of CXCR4 associated with better relapse-free survival (p = 0.032), but not after adjusting for vascular invasion. Patients with higher beta-catenin scores showed a tendency for poorer relapse-free survival (p = 0.056). MECA-79 immunoexpression was absent., Conclusions: The informative protein biomarkers (i.e., MIB-1, CXCL12, beta-catenin, and possibly CXCR4) may prove useful for risk-stratifying patients if validated in larger, multicentric and well-defined studies. Currently, classical histopathological features of testicular germ cell tumors remain key for relapse prediction.

Purpose: We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections., Materials and Methods: Retrospective review of the Indiana University testis cancer database identified patients who underwent primary retroperitoneal lymph node dissection between January 2007 and December 2017. Patients and providers were contacted to obtain information regarding adjuvant therapy, recurrence and survival. The primary outcome was recurrence-free survival. Kaplan-Meier curves assessed survival differences stratified by pathological stage, template of dissection and use of adjuvant chemotherapy., Results: A total of 274 patients were included in the study. Most men presented with clinical stage I disease (214, 78%). A modified unilateral template was performed in 257 (94%) and bilateral template in 17 (6%). Overall 148 (54%) and 126 (46%) men had pathological stage (PS) I and PS-II disease, respectively. Thirteen patients (10%) with PS-II disease were treated with adjuvant chemotherapy. With a median followup of 55 months only 33 (12%) patients had recurrence. Of the 113 patients with PS-II disease who did not receive chemotherapy 21 (19%) had disease relapse and 81% were cured with surgery alone and never had recurrence. No difference in recurrence-free survival was noted between modified and bilateral template dissections., Conclusions: The use of adjuvant chemotherapy has been minimal during the last decade. The majority (81%) of men with PS-II disease were cured with retroperitoneal lymph node dissection alone and were able to avoid chemotherapy. Modified unilateral template dissection provided excellent oncologic control while minimizing morbidity.

Background: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus., Materials and Methods: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates., Results: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups., Conclusions: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Background: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients., Methods: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS)., Results: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047)., Conclusions: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The role of retroperitoneal lymph node dissection (RPLND) as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomatous germ-cell tumors. We describe utilization of primary RPLND in the United States and report on overall survival (OS) after surgery for these men., Patients and Methods: Using 2004-2014 data from the National Cancer Data Base, we identified 62,727 men with primary testicular cancer, 31,068 of whom were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminomatous germ-cell tumor histologies, those who did not undergo RPLND, those where clinical stage and survival data were unavailable, and those with testicular seminoma who underwent RPLND in the postchemotherapy setting (n = 47), 365 men comprised our final cohort. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine OS., Results: A total of 365 men with testicular seminoma underwent primary RPLND. At a median follow-up of 4.1 years, there were 16 deaths in the entire cohort. Five-year OS was 94.2%. Subset analysis of men with stage I and IIA/B disease who underwent primary RPLND revealed 5-year OS rates of 97.3% and 92.0%, respectively (P = .035). OS did not significantly differ in patients with stage IIA versus IIB disease (91.8% vs. 92.3%, respectively, P = .907)., Conclusion: Although RPLND is rarely used as primary therapy in testicular seminoma, OS rates appear to be comparable to rates reported in the literature for primary chemotherapy or radiotherapy. Ongoing prospective trials will clarify the role of RPLND in the management of testicular seminoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients., Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study., Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007)., Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

Introduction: Approximately one-fourth of patients with clinical stage I testicular germ cell cancer will relapse within 5 years of follow-up. Certain histopathological features in the primary tumour have been associated with an increased risk of relapse. The available evidence on the prognostic value of the risk factors, however, is hampered by heterogeneity of the study populations included and variable reporting of the histopathological features. The aim of this study is to identify pathological risk factors for relapse in an unselected large nationwide cohort of patients with stage I disease., Methods and Analysis: All incident cases of stage I testicular germ cell cancer diagnosed in Denmark between 2013 and 2018 will be identified using the nationwide prospective Danish Testicular Cancer (DaTeCa) database. Archived microscopic slides from the orchiectomy specimens will be retrieved through linkage to the Danish Pathology Data Bank and reviewed blinded to the clinical outcome. The DaTeCa database includes 960 stage I seminoma patients with expected 185 relapses and 480 patients with stage I non-seminoma with expected 150 relapses. A minimum follow-up period of 3 years of all patients will be ensured. Predefined prognostic variables will be investigated with regard to relapse in univariable and multivariable analysis using the Cox proportional hazards model., Ethics and Dissemination: This study protocol has been approved by the Regional Ethics Committee (Region Zealand, Denmark) and the Danish Data Protection Agency. All data will be managed confidentially according to legislation. Study results will be presented at international conferences and published in peer-review journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We comprehensively tested contemporary incidence and mortality rates in patients with germ cell tumor of the testis (GCTT)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2015), statistical analyses included estimated annual percentage changes, multivariable logistic regression (MLR) models, Kaplan-Meier curves, and multivariable Cox regression (MCR) models., Results: Of 13,114 GCTT patients, 7954 (60.6%) harbored seminoma germ cell tumors of the testis (SGCTT) and 5160 (39.4%) non-SGCTT (NSGCTT). Relative to SGCTT, NSGCTT patients harbored more advanced stage (for stage III 824 [16.0%] vs. 279 patients [3.5%]; P < .001). In MLR, higher rates of stage II/III affected those with never-married status (odds ratio [OR], 1.6; P < .001) and African American ethnicity (OR, 1.5; P = .005) for SGCTT and never-married (OR, 1.3; P = .002) and Hispanic ethnicity (OR, 1.3; P < .001) for NSGCTT. Significant differences in 5-year cancer-specific mortality (CSM) distinguished SGCTT (stage I: 0.4; stage II: 3.4; stage III: 11.4%; P < .001) from NSGCTT (stage I: 1.6; stage II: 2.5; stage III: 22.2%; P < .001). In MCR, unmarried status independently predicted higher CSM for SGCTT (hazard ratio [HR], 2.1; P = .007) and NSGCTT (HR, 1.9; P < .001)., Conclusion: Stage I and stage III NSGCTT survival is worse, than for SGCTT. Never-married, Hispanic, and African American individuals are at higher risk of more advanced stage and/or CSM in SGCTT and NSGCTT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and objectives: The aim of this study was to analyze trends in testicular cancer incidence, mortality, and survival in Lithuania during the period 1998-2013. Materials and Methods: The study was based on all cases of testicular cancer reported to the Lithuanian Cancer Registry between 1998 and 2013. Age group-specific rates and standardized rates were calculated using the direct method (European standard population). The Joinpoint regression model was used to provide the annual percentage change (APC). Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. Results: During the study period, the age-standardized incidence rate of testicular cancer increased from 1.97 to 3.45 per 100,000, with APC of 2.97% (95% CI 0.9 to 5.1). Incidence rate of seminomas changed from 0.71 to 1.54 per 100,000, with APC of 2.61% (95% CI -0.4 to 5.7), and the incidence rate of non-seminomas increased from 0.84 to 1.83 per 100,000, with APC of 4.16% (95% CI 1.6 to 6.8). The mortality rate of testicular cancer in Lithuania during this period declined from 0.78 to 0.51 per 100,000, with APC of -2.91% (95% CI -5.5 to -0.3). Relative five-year survival ratio for the period 2009-2013 was 89.39% (95% CI 82.2 to 94.4). In our study, the overall five-year relative survival increased slightly (10.1%) from 2004-2008 to 2009-2013 (from 79.3% to 89.4%). Conclusions: A moderate increase of testicular cancer incidence has been observed in Lithuania between the years 1998 and 2013, while the mortality rate decreased. The five-year relative survival increased according to different period estimates; however, the results could have been higher if a multidisciplinary approach to diagnostics and management in the concerned centers had been implemented in Lithuania as in other countries., Competing Interests: The authors declare no conflict of interest.

Background: We tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM., Results: Of all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: -3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5)., Conclusion: Surveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.

While treatment for testicular cancer (TC) has become standardized after the 1980s with an associated significant improvement in patient survival, this has been accompanied by an increased risk of second primary cancers (SPCs). Patients were identified from the Swedish Cancer Registry spanning the years from 1980 to 2015, including 8788 individuals with primary TC and their SPCs. Relative risks (RRs) for SPC were calculated using the generalized Poisson regression model. SPCs were diagnosed in 9.4% of patients with TC and half of them were late onset cancers not common in the population in their 40s. Overall RR of SPCs (excluding second TC) was 1.30 (95%CI: 1.20-1.40), including high risks for seven solid cancers, non-Hodgkin lymphoma and leukemia. Second TC was the most common SPC and the RR of 17.19 (95%CI: 14.89-19.85) was the highest recorded. Cancers known to be fatal as first primary cancers were also fatal as SPC in TC patients. Survival at 30 years of follow-up was approximately 80% for TC patients without SPC but it decreased to 40% for patients with SPC. The unexpected finding that half of the identified SPCs were typical late onset cancers in the middle-aged population raises concerns that therapy may facilitate premature aging. The risks of SPC are clinically important for the long-term management of TC patients and the high-mortality calls for a future management strategy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: There is no consensus regarding the management of Stage 1 seminomas following inguinal orchiectomy. In this study, we evaluated the treatment results and treatment-related toxicity for patients with Stage 1 seminomas treated with adjuvant radiotherapy (RT) at a single institution., Methods: Sixty-five patients who underwent adjuvant RT following orchiectomy for Stage 1 seminomas between January 1996 and December 2007 were retrospectively reviewed. The age, tumor location, histopathological type, stage, tumor size, RT field, and radiation dose were recorded for all patients., Results: The patients' ages ranged from 17 to 61 years (median, 37 years). Sixty-three patients (97%) were diagnosed with classical seminoma and the remaining two patients (3%) had spermatocytic seminoma. After orchiectomy, 37 patients (57%) received para-aortic RT and 28 patients (43%) received dog-leg field RT. RT was applied with 1.8-2 Gy/day fractionation and the median RT dose was 26 Gy (range, 20-38). Follow-up ranged from 0.3 to 18 years (median, 9.5 years). Local control had been achieved in all patients and all of them were alive with no evidence of disease. Fifty-one patients (77%) had at least 5 years of follow-up and 27 patients (41%) had at least 10 years of follow-up. Overall survival at 10 years was 100%., Conclusion: Although retrospective in nature, this single-institutional study provides useful information about the outcomes and toxicities associated with adjuvant RT in patients with Stage 1 seminomas reporting excellent disease control and survival rates at the expense of acceptable toxicity., Competing Interests: None

Introduction: Maintenance of chemotherapy dose intensity is a cornerstone of management in testicular germ cell tumors. We describe chemotherapy delivery and outcomes of patients in routine practice., Methods: The Ontario Cancer Registry was linked to electronic records of treatment to identify patients diagnosed with testicular cancer treated with orchiectomy and chemotherapy from 2005 to 2010. We describe chemotherapy delivery and dose intensity. Overall survival was measured from the start of chemotherapy., Results: During the study period, 552 new cases of testicular cancer were treated with orchiectomy and chemotherapy; drug/regimen details were available for 475 (86%) cases. The study population included 324 patients with nonseminoma and 151 with seminoma. The majority of patients were treated with bleomycin, etoposide, and cisplatin (BEP) (83%, 394/475) or etoposide and cisplatin (EP) (6%, 30/475); 89% (379/424) received 3 to 4 cycles of treatment. Thirty two percent of all BEP patients (125/394) had at least 1 dose omission of bleomycin; this rate increased to 51% of patients treated with BEP × 4. Eight percent (33/397) of evaluable BEP/EP patients had a dose reduction/omission of cisplatin and 21% (82/397) had a dose delay of >6 days. Among the BEP/EP cases, 44% (174/397) had reduced chemotherapy dose intensity. Five-year overall survival for all cases was 95%., Conclusions: Almost half of patients treated with BEP/EP chemotherapy in routine practice have some form of reduced chemotherapy delivery. Despite this, long-term survival in the general population is very high. Further studies are required to understand the extent to which dose delivery might influence outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The recent 8th edition of the American Joint Committee on Cancer (AJCC) staging manual had multiple changes concerning how pathologists should stage germ cell tumors (GCTs) of the testis. A significant one concerns the impact of different types of spermatic cord involvement, specifically direct tumor extension versus discontinuous involvement by invasion through lymphovascular spaces. We compared clinicopathologic findings and outcome data between 2 cohorts with these findings to evaluate the validity of the change in the AJCC 8th edition manual. GCTs (seminomatous and nonseminomatous) of the testis were identified that had previously been staged as pT3 due to involvement of the spermatic cord. Pathologic, radiographic, and clinical findings were reviewed. Tumors were restaged based on AJCC 8th edition criteria and the cohorts were split into direct extension by tumor into the spermatic cord (pT3), spermatic cord soft tissue invasion via spread from discontinuously involved lymphovascular spaces (pT2pM1), or a combination of both (pT3pM1). One hundred cases of primary GCTs of the testis, previously classified as pT3 by the AJCC 6th or 7th cancer staging manuals from 2007 to 2015, were selected. Mixed malignant GCTs were the predominant tumor type, comprising 66% of all cases. Pure tumor morphologies included embryonal carcinoma (n=17), seminoma (n=14), teratoma (n=2), and yolk sac tumor (n=1). The tumors either directly invaded into the spermatic cord (n=78), involved the cord discontinuously via spread from lymphovascular spaces (n=18), or had both findings (n=4). Overall, 93% of patients presented at advanced clinical stage (CS). Using the AJCC 8th parameters, 12% of all tumors were upstaged. Changes included CSI (n=1) and CSII (n=11) tumors being reclassified as prognostic stage group III. Clinical and/or pathologic recurrence was identified in 19% of all patients, including 12 pT3 and 7 pM1 patients (P=0.11). Overall mean time to recurrence was 24.6 months, with a mean of 28.0 months for pT3 tumors and 18.9 months for pM1 tumors. Five patients were dead at the time of this study, including 3 (4%) with pT3 tumors and 2 (9%) in the pM1 cohort. Our findings support that seminomatous and nonseminomatous GCTs with spermatic cord invasion have a high frequency of advanced CS at presentation, regardless of involvement by direct extension or discontinuous spread via invasion from lymphovascular spaces. By designating the latter as M1, a spurious upstaging to prognostic stage group III is required by the AJCC 8th edition. We were unable to identify statistically significant difference between the 2 groups as it pertained to CS at presentation and likelihood of recurrence. Conversely, statistical trends favor that pM1 patients have more likely recurrence and worse prognosis than pT3 patients.

Testicular germ-cell cancer (GCC) is a curable disease. Stage I patients are mostly cured by surgery alone. For those with good prognosis advanced disease, radiotherapy in some patients with stage II Seminoma and chemotherapy for all other patients, are responsible for 95% of long-term survivors. Unfortunately, despite this high level of curability, overall survival has been reported lower for those patients receiving either radiotherapy or chemotherapy versus patients treated by surgery alone. Long-term survivors face a higher incidence of second neoplasms, and a higher risk of cardiovascular disease and metabolic syndrome than expected. Other non-life-threatening toxicities such as ototoxicity, neurotoxicity and fertility problems are common. This paper reviews the potential causes of the higher mortality among long-term survivors of testicular tumors, the incidence of them and some recommendations for the diagnoses and prevention of long-term sequelae in patients with GCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: While retroperitoneal lymph node dissection (RPLND) is traditionally reserved for nonseminomatous germ cell tumors, recent efforts to reduce long-term toxicities of radiation and chemotherapy have turned attention to its application for testicular seminomas. Currently, RPLND is reserved for the post-chemotherapy for stage II testicular seminomas; we aimed to describe current utilization of RPNLD for testicular seminomas by stage and implications for survival., Methods: A national sample of men diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminoma (1988-2013) was evaluated from SEER Program registries. Stage-specific utilization of RPLND was determined. Cox proportional hazards models, adjusted for age, race, and radiotherapy, evaluated overall (OS) and cancer-specific survival (CSS) for the RPLND cohort. Adjusted models assessed predictors of RPLND., Results: A total of 17,681 men (mean age 38.1 years) with testicular seminoma were included with low utilization of RPLND for stage I disease (1.3% overall) and higher rates for stage II disease (10.6% overall). There were no appreciable trends over time. Patients receiving RPLND did not appear to have worse OS or CSS on adjusted stage-by-stage analysis. Higher stage disease (IIA-IIC) was associated with greater need for RPLND while radiotherapy was associated with decreased use [OR 0.40 (0.32-0.51), p < 0.001]., Conclusions: Utilization of RPLND for testicular seminomas in the post-chemotherapy setting has remained stable over a 25-year period. Patients undergoing RPLND are a higher risk cohort but stage-by-stage survival outcomes appeared comparable to men not undergoing RPLND. Upcoming trials implementing RPLND as a first-line modality for testicular seminoma or isolated retroperitoneal relapse will help better quantify relative recurrence and survival.

Introduction: Testicular seminoma affects relatively young men with excellent survival outcomes. There has been increasing concern that radiotherapy (RT) leads to secondary malignant neoplasms (SMNs) and subsequent mortality. We evaluated the effect of RT on incidence of SMNs and quantified cancer-related mortality and other causes of death for patients with stage I and II testicular seminoma., Material and Methods: A national sample of men (1988-2013) diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminomas from Surveillance, Epidemiology, and End Results were evaluated. Use of RT over time and survival curves (5/10/15-year) was stratified by stage. Log-binomial regression determined relative risk of developing SMNs. Incidence rate ratios (IRR) and age-adjusted Cox proportional hazards models compared overall, cancer-specific survival (CSS), and other cancer-specific survival. Competing-risks regression generated cumulative incidence functions. Prevalence ratios explored excess deaths owing to specific causes., Results: A total of 16,463 men were included with 9,126 (55.4%) undergoing RT with markedly decreased use for stage I seminoma in recent years (<20%) and ~50% for stage IIA. RT increased risk of SMNs (relative risk = 1.84 [95% CI: 1.61-2.10, P<0.01]). Survival rates were excellent (15-year CSS for stage I [≥99%], stage IIA [98.1%], stage IIB-C [96%-97%]). RT was associated with improved CSS for stage IB and IIA, but demonstrated less benefit for stage IA (IRR = 0.63 [95% CI: 0.35-1.14, P = 0.10]) with worse other cancer-specific survival (IRR = 1.80 [95% CI: 0.97-3.59, P = 0.05]). Gastrointestinal, respiratory, urinary, and hematologic malignances accounted for 84% of SMN deaths., Conclusions: RT offers excellent CSS for men with stage I/II seminoma and an increased risk of SMN later in life. Future studies should better evaluate risk-stratification for stage IB patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly there are fewer data reported on the AYA experience with testicular seminoma., Objective: To evaluate national trends in postoperative treatment and overall survival (OS) outcomes in testicular seminoma by age group, specifically comparing AYAs with older adults., Study Design: The National Cancer Data Base (NCDB) was queried for patients with testicular seminoma diagnosed between 2004 and 2012, who underwent orchiectomy followed by observation or adjuvant therapy (chemotherapy, radiation (RT), or both). Patients were grouped by age: AYA (15-39 years), adults between 40 and 55 years, and adults >55 years. Overall survival (OS) was presented using Kaplan-Meier curves and groups compared via a log-rank test. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Binary multiple logistic regression identified differences in variables by age category., Results: Of the total 22,361 patients the majority were AYAs (12,880, 57.6%), followed by adults 40-55 years (8,022, 35.9%), and >55 years (1,459, 6.5%). Unadjusted 5-year OS was significantly better for AYAs versus adults 40-55 years and >55 years (98.0%, 96.4%, 87.7%; p < 0.001), as was 10-year OS (96.1%, 91.8%, 71.3% respectively; p < 0.001). The Table shows that on a MVA, OS was significantly better for AYAs versus adults 40-55 years and adults >55 years. AYA patients were also more commonly treated at centers with greater clinical volume. Additionally, AYA patients were less likely to present with metastatic disease. Accordingly, AYA patients were less likely to undergo retroperitoneal lymph node dissection (OR 0.81; p = 0.001) and were less often managed with adjuvant therapy including chemotherapy (OR 0.91; p = 0.027), RT (OR 0.93; p = 0.025), or both (OR 0.68; p = 0.020)., Discussion: AYA patients with testicular seminoma present with earlier stage disease and in the clinical Stage I setting are more often are managed with active surveillance following orchiectomy when compared with older adults in this population-based analysis. Among AYA patients, OS was modestly better when compared with adults 40-55 years and significantly better when compared with adults >55 years., Conclusion: Our objective to describe the patterns of care and survival outcomes for AYA patients with testicular seminoma in the USA was met by reviewing this large national dataset. These results may inform future guidelines for management of AYA seminoma., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Clinical stage I represents the most frequent presentation of both seminoma and nonseminoma testicular cancer. Despite a survival rate of close to 100%, the management of patients with this disease stage is controversial. The recurrence rate is 10% to 20% for patients with stage I seminoma and 15% to 50% for those with stage I nonseminoma. A highly sensitive and specific biomarker of relapse that is applicable to both seminoma and nonseminoma, and able to drive a definitive risk-adapted management of the patients, still is not available. Lymphovascular invasion (LVI) in the orchiectomy specimen has been used as a risk factor in patients with stage I nonseminoma. However, with a risk of recurrence of 50% for LVI-positive patients and 15% for LVI-negative patients, the discriminative power of LVI is modest at best. Various management options exist. In the absence of a predictive biomarker for recurrence, active surveillance avoids overtreatment in 50% to 85% of patients, with no risk of long-term side effects in nonrelapsing patients and a preserved overall survival of almost 100% after specific treatment for recurrent disease. However, although active surveillance has been accepted as the preferred option for stage I seminoma and low-risk stage I nonseminoma, its role in high-risk stage I nonseminoma remains controversial.

Background: The optimal treatment strategy for patients with clinical stage I (CS-1) seminoma is controversial. The objective of the current study was to evaluate the outcomes for patients considered to be at high risk of disease recurrence with a tumor size ≥6 cm. Patients were treated with either adjuvant radiotherapy (RT) or followed with surveillance., Methods: From the Danish Testicular Cancer database, the authors identified 473 patients with CS-1 seminoma with a tumor size ≥6 cm. Of these, 254 patients underwent adjuvant RT and 219 were followed with surveillance. Cumulative incidence function was applied to estimate the risk of disease recurrence, risk of second malignant neoplasm, and risk of receiving >1 line of treatment. Survival of the 2 groups was compared with the log-rank test and Cox model including age at diagnosis., Results: No significant differences were found with regard to overall survival or risk of a second malignant neoplasm. Patients undergoing adjuvant RT received more treatments per patient than patients followed with surveillance, but there was no significant difference noted with regard to the risk of receiving >1 line of treatment. The 10-year cumulative incidence of disease recurrence was 32% versus 2.8%, respectively, for patients followed with surveillance and adjuvant RT. In patients followed with surveillance who developed disease recurrence, there was a high incidence of second recurrences after RT., Conclusions: The 10-year overall survival was found to be similar irrespective of primary treatment. Adjuvant RT was found to effectively reduce the rate of disease recurrence but resulted in the overtreatment of approximately two-thirds of the patients. The high incidence of second disease recurrences after RT in the patients followed with surveillance needs be addressed in future studies. Cancer 2017;123:1212-1218. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses were detected by computed tomography scan during routine follow-up, 98% in the International Germ Cell Cancer Collaborative Group good prognosis group. Chemotherapy was administered to 92% of patients, mostly as standard first-line treatment corresponding to stage; 8% of patients had additional local treatments. Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of 185 patients were alive without disease, and four patients with disease. Seven patients died, three of whom due to progressive disease. Conclusion Within the limitations of a retrospective analysis, the results suggest that the majority of patients who experience a relapse after adjuvant carboplatin for clinical stage I seminoma can be successfully treated with a cisplatin-based chemotherapy regimen adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant treatment, a minimum of 5 years follow-up is recommended.

Objectives: - To assess the medical insurance risk for patients with stage I testicular cancer (TC), by calculating the overall mortality risk with and without relapse, and compare it to men from the Danish population., Background: - Testicular cancer is the most common malignancy in young males. Outcomes of a Danish cohort of 3366 patients with stage I TC (1366 non-seminomas (NSTC) and 2000 Seminomas (STC)), were analyzed., Method: - The data were analyzed by the "illness-death" model. For the analysis of the transitions between diagnosis, relapse and death we adopted a parametric approach, where the relationship between the intensities and the effect of covariates were specified by Poisson regression models for NSTC and STC individually., Results: - In the NSTC group, 422 patients relapsed. Six relapses (1.4%) occurred after 5 years of follow-up. In the STC group, 389 relapsed. The relapse rate after 5 years was 4.1%. The overall mortality analyses showed that the standardized mortality ratio (SMR) for men with NSTC without relapse, was slightly lower than in the matched general population of Danish men (SMR = 0.9). In STC patients without relapse, SMR was 0.80. Relapse raised the overall mortality by a factor 2.0 for NSTC and 1.5 for STC., Conclusions: - The fact that few relapses occur 5 years after diagnosis is an important finding for risk assessment in life insurance. It makes it possible to insure men diagnosed with stage I TC, who have not experienced relapse 5 years after diagnosis, on normal terms.

Aim: To report long term oncologic outcomes after adjuvant radiotherapy (RT) for stage I seminoma., Method: We reviewed the complete data set for all patients treated at our institute between 1988 and 2005 for stage I seminoma with adjuvant RT after radical orchiectomy ., Results: A total of 85 patients were included. The median follow-up was 15 years. The 20-year overall survival (OS) and relapse free survival (RFS) were 92% and 96.3%, respectively. No severe acute and late complications were recorded. Overall 5.9% of patients had a second unrelated malignancy., Conclusion: Adjuvant RT is an efficacious and safe treatment in stage I seminoma.

Purpose/objective: Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease., Methods and Materials: Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed., Results: A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P < .01) and community treatment setting (OR, 1.81-2.76; P < .01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P < .01), more recent year of diagnosis (continuous OR, 0.93; P < .01), and primary pathologic tumor 3/4 stage (OR, 0.47; P < .01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P < .01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P < .01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08)., Conclusions: Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were associated with type of postoperative therapy. Longer follow-up to account for potential late effects of treatment is needed., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

Background: Comprehensive data on late relapse (LR) and very LR (VLR) in patients with clinical stage I (CS-1) testicular cancer followed on surveillance are missing. These data are essential for planning optimal follow-up., Objective: Assess incidence and outcome of LR (>2 yr) and VLR (>5 yr) in a large cohort of CS-1 surveillance patients, and examine differences in the clinical characteristics of patients with early relapse (ER), LR, and VLR., Design, Setting, and Participants: CS-1 surveillance patients diagnosed between 1984 and 2007 were identified from the retrospective Danish Testicular Cancer (DaTeCa) database., Outcome Measurements and Statistical Analysis: We estimated survival and relapse probabilities and compared the results using log-rank tests and Cox regression analyses. We compared differences in patient characteristics by using χ(2), Fisher exact, and Mann-Whitney tests., Results and Limitations: Our study included 3366 (2000 seminoma and 1366 nonseminoma) patients. Median follow-up was 15 yr. Five-year conditional risk of LR was 5.0% and 2.1% for seminoma and nonseminoma patients, respectively. There were no significant differences in disease-specific or overall survival when comparing the LR(VLR) and ER patients by log-rank, but Cox regression adjusted for age showed a significant effect of time to relapse on survival for seminoma patients. Apart from significantly more ER nonseminoma patients with elevated human chorionic gonadotropin at relapse, there were no significant differences in patient characteristics at orchiectomy or relapse. Limitations include retrospective design and exclusion of patients who had been offered adjuvant therapy., Conclusions: The risk of VLR is minimal, and the patients carry a good prognosis. Patient characteristics of CS-1 surveillance patients with LR(VLR) do not differ significantly from patients with ER., Patient Summary: We compared stage I testicular cancer surveillance patients with early relapse (ER) versus late relapse (LR; >2 yr). LR patients as a group did no worse than ER patients, although increased time to relapse was negatively associated with survival for seminoma patients., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims: Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner., Materials and Methods: Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival., Results: The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis., Conclusions: Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Testicular cancer is the most common cancer among adolescent and young adult (AYA) men 15-39 years of age. This study aims to determine whether race/ethnicity and/or neighborhood socioeconomic status (SES) contribute independently to survival of AYAs with testicular cancer., Methods: Data on 14,249 eligible AYAs with testicular cancer diagnosed in California between 1988 and 2010 were obtained from the population-based California Cancer Registry. Multivariable Cox proportional hazards regression was used to examine overall and testicular cancer-specific survival and survival for the seminoma and nonseminoma histologic subtypes according to race/ethnicity, census-tract level neighborhood SES, and other patient and clinical characteristics., Results: Compared with White AYAs, Hispanic AYAs had worse overall and testicular cancer-specific survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07-1.37) and Black AYAs had worse overall survival (HR, 1.41; 95% CI, 1.01-1.97), independent of neighborhood SES and other demographic and clinical factors. Racial/ethnic disparities in survival were more pronounced for nonseminoma than for seminoma. AYAs residing in middle and low SES neighborhoods experienced worse survival across both histologic subtypes independent of race/ethnicity and other factors, while improvements in survival over time were more pronounced for seminoma. Longer time to treatment was also associated with worse survival, particularly for AYAs with nonseminoma., Conclusion: Among AYAs, race/ethnicity, and neighborhood SES are independently associated with survival after testicular cancer. Variation in disparities by histologic type according to demographic factors, year of diagnosis, and time to treatment may reflect differences in prognosis and extent of treatment for the two histologies.

Purpose: To analyze, in the setting of stage I seminoma, the factors affecting adjuvant treatment decisions and resulting survival outcomes, using a national dataset., Methods and Materials: We identified 33,094 stage I seminoma patients after orchiectomy from 1998 to 2012 from the National Cancer Data Base. Factors affecting treatment selection (active surveillance [AS] vs adjuvant treatment [AT]) were identified using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for chemotherapy [CT] versus radiation therapy [RT]., Results: Only 33% of patients received AS, and 65% received AT (89% RT and 11% CT). From 1998 to 2012 the proportion receiving AS increased from 23% to 60%, whereas RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Utilization of low-dose RT increased from 1.5% in 1999 to 34% in 2012. There was a small absolute overall survival advantage to AT over AS at 10 years (95.0% vs 93.4%, propensity adjusted hazard ratio 0.58, P<.0005)., Conclusions: There has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemogrpahic and clinicopathologic factors. Between AT options, there has been significant increase in use of CT, mirrored by a decline in use of RT. Although overall survival remains high for all 3 treatment strategies, AT seems to be associated with a small absolute survival advantage over AS up to 10 years out from diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Active surveillance is an increasingly accepted approach for managing patients with germ-cell tumors (GCTs) after an orchiectomy. Here we investigate a time-to-relapse stratification scheme for clinical stage 1 (CS1) nonseminoma GCT (NSGCT) patients according to factors associated with relapse and identify a group of patients with a lower frequency and longer time-to-relapse who may require an alternative surveillance strategy., Patients and Methods: We analyzed 266 CS1 GCT patients from the IRB-approved DFCI GCT database that exclusively underwent surveillance following orchiectomy from 1997 to 2013. We stratified NSGCT patients according to predominance of embryonal carcinoma (EmbP) and lymphovascular invasion (LVI), using a 0, 1, and 2 scoring system. Cox regression and conditional risk analysis were used to compare each NSGCT group to patients in the seminomatous germ-cell tumor (SGCT) category. Median time-to-relapse values were then calculated among those patients who underwent relapse. Relapse-free survival curves were generated using the Kaplan-Meier method., Results: Fifty (37%) NSGCT and 20 (15%) SGCT patients relapsed. The median time-to-relapse was 11.5 versus 6.3 months for the SGCT and NSGCT groups, respectively. For NSGCT patients, relapse rates were higher and median time-to-relapse faster with increasing number of risk factors (RFs). Relapse rates (%) and median time-to-relapse (months) were 25%/8.5 months, 41%/6.8 months and 78%/3.8 months for RF0, RF1 and RF2, respectively. We found a statistically significant difference between SGCT and patients with one or two RFs (P < 0.001) but not between SGCT and NSGCT RF0 (P = 0.108)., Conclusion: NSGCT patients grouped by a risk score system based on EmbP and LVI yielded three groups with distinct relapse patterns -and patients with neither EmbP nor LVI appear to behave similar to SGCT., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The aim of our study was to identify factors which influence survival in patients with disseminated seminoma in the good prognostic group according to IGCCCG, as well as to evaluate the impact of treatment intensification in patients with negative prognostic factors., Methods: We analyzed the database of the patients with metastatic seminoma who had received treatment at our department from 1986 to 2005. Inclusion criteria were as follows: morphologically verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy regimen (EP ± bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The primary endpoint was overall survival (OS)., Results: With median follow-up 83 months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01), pulmonary metastases (p < 0.01) and LDH level ≥ 2.25 × ULN (p = 0.01). In view of the obtained data, we have changed our treatment approach since 2005. In case of any negative prognostic factors, we administered an intensified CT regimen--4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with unfavorable prognosis. We observed an increase of 5-year OS rate in the intensified CT group in comparison with the standard CT group in patients with unfavorable prognostic from 85 to 100%., Conclusion: Administration of 4 cycles of induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have LDH level ≥ 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary metastases results in decreased disease progression rate and significant gain in OS.

Purpose: Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT), and adjuvant chemotherapy has been accepted in high-risk CSI NSGCTT. Because of the late toxicity of standard radiotherapy in CSI testicular seminoma (SGCTT), this therapeutic approach has been accepted also in the management of CSI SGCTT. In the current study, we analyzed single-center experience with risk-adapted therapeutic approaches (active surveillance and adjuvant chemotherapy) in patients with CSI SGCTT., Patients and Methods: The study analyzed a total of 90 patients collected at a single center from April 2008 to March 2015 with CSI SGCTT who were stratified into two groups according to risk-adapted therapeutic approaches., Results: In the group A (low-risk CSI SGCTT-no rete testis invasion, tumor size <4 cm, pT1 stage), which consisted of 74 patients who underwent surveillance, relapse occurred in seven (9.5 %) patients after a mean follow-up of 14.5 months. In the group B (high-risk CSI SGCTT-rete testis invasion, tumor size >4 cm or pT ≥ 2 stage), which consisted of 16 patients who were treated with adjuvant chemotherapy, relapse occurred in two (12.5 %) patients after a mean follow-up of 13.8 months. Overall survival of patients in both groups was 100 %. The statistically significant difference in progression-free survival between these two groups was not found., Conclusions: Radiotherapy is currently not recommended as an adjuvant treatment in CSI SGCTT patients. The benefit of using risk-adapted therapeutic approaches in CSI SGCTTs patients is evident.

Introduction and Objective: The objective of this study was to assess the oncological results of a population of patients which undergo surveillance after diagnosis of stage I testicular seminoma (2, 5 and 8 years overall, specific and recurrence free survival). We also research recurrence risk factors., Patients and Methods: We have looked at the data of all patients treated in our center since 1993 for a grade I testicular seminoma. We focused on age at diagnosis, biological (tumoral markers) and pathological (tumor size, rete testis, lymphovascular, tunica albuginea or spermatic cord invasion) data. During surveillance, we noted the number, the localization and the interval until recurrence and death. We calculated 2, 5 and 8 years overall, specific and recurrence-free survival and searched recurrence risk factors., Results: Sixty-nine patients (mean age: 37) were followed during a mean time of 97 months. Sixty-three per cent of the tumours were less than 4 cm (50 lesions). Lymphovascular, rete testis, spermatic cord and tunica albuginea invasion were present in respectively 21%, 33%, 4% and 29% of the cases. LDH and HCG were above normal rate in respectively 44 and 27% of the cases. Eighteen patients (23%) relapsed at a mean time of 12 months. Recurrence-free survival was respectively 81%, 77% and 77% at 2, 5 and 8 years. Tumor size<4 cm (P = 0.002), rete testis invasion (P = 0.03) and stage ≥ pT2 (P = 0.012) were associated with recurrence in univariate analysis. Using multivariate analysis, only tumor size >4 cm was a recurrence risk factor (risk multiplied by 3). At the end of the study, 77 patients are alive (97.5%). Overall and specific survival was 97.5% at 2, 5 and 8 years., Conclusion: We show here the interest of surveillance in case of stage 1 testicular seminoma. The overall and specific survivals are the same as after chemotherapy or radiotherapy. Furthermore, we confirm the role of tumor size to stratify recurrence risk., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma., Materials and Methods: Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy., Results: The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042)., Conclusion: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.

A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1-10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To evaluate post-orchiectomy utilization of radiation therapy (RT) versus other management approaches in stage IIA and IIB testicular seminoma patients., Materials and Methods: Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER) database., Results: Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72 % vs. 46 %, respectively; P < 0.001). There was no significant change in RT utilization for stage IIA or IIB disease between 1988 and 2003 (P = 0.89)., Conclusions: Between 1988 and 2003, stage IIA patients underwent RT more often than stage IIB patients in the United States. There was no significant change in RT utilization for stage IIA or IIB disease during this time period. Based on reports describing excellent progression-free survival with cisplatin-based chemotherapy, this approach has increased in popularity since 2003 and may eventually become the most popular treatment approach for both stage IIA and IIB testicular seminoma.

Objective: To determine if utilization of surveillance or adjuvant chemotherapy has increased compared with that of adjuvant radiotherapy (ART) in clinical stage I seminoma (CSIS) and to estimate the impact of this utilization trend on secondary malignancies., Methods: The National Cancer Data Base, a web-based data analysis tool was examined for first-course adjuvant therapy management in CSIS from 2000 to 2008. We assessed the utilization in academic vs community practice settings and changes in tumor stage. We also estimated the number of secondary malignancies based on the change in practice., Results: There were 52,672 patients of testicular cancer diagnosed. Of those, 28,974 (55.0%) patients had seminoma with 22,210 (84.2%) patients classified as CSIS. Overall, 14,005 (65.4%), 6430 (30.1%), and 951 (4.4%) patients received ART, surveillance, and adjuvant chemotherapy (AC), respectively. In 2000, most patients received ART (71.7%), followed by surveillance (26.5%), and AC (1.9%). In 2008, the majority of patients still received ART (47.7%) but surveillance (39.6%) and AC (12.6%) totaled a larger proportion. We calculated that this ART utilization rate would lead to an additional 372 solid tumor cases per year, 40 years later, whereas the current surveillance rate would lead to 34 cases of secondary malignancy annually in the United States., Conclusion: ART was the leading adjuvant management strategy for CSIS, but its share drastically decreased with a concomitant increase in surveillance and AC, particularly after 2004. These trends were similar in both academic and community settings. The current level of ART, although decreasing, may nevertheless lead to additional cases of solid cancer comparable with testicular cancer deaths., (Published by Elsevier Inc.)

Unlabelled: The aim of this study is to report treatments results of patients with primary germ cell tumors (GCTs) of mediastinum., Methods: A retrospective review was done of 19 consecutive patients with mediastinal GCTs treated in "Institut de cancérologie de Lorraine" between 1990 and 2012., Results: A total of 19 patients were enrolled in this study. Three patients had pure seminoma and 16 patients had non-seminomatous germ cell tumors. All patients were treated with cisplatinum based chemotherapy at a dose of 33.48 mg/m(2)/week. At the end of chemotherapy, three patients (15.8%) had complete response and negative marker, seven of them (36.8%) had partial response and negative marker, five of them (26.32%) had partial response and positive marker, three of them (15.8%) had progressive disease (refractory disease) and one patient died because of the disease during treatment. The 1-year and 5-year overall survival rates were respectively 78 and 36% and the progression-free survival rate was 43%. When relapse occurred, this happened within a 13 month period., Conclusion: Our study confirmed the good management of mediastinal GCTs in our institute with similar results compared to literature.

Purpose: Viable seminoma encountered at post-chemotherapy retroperitoneal lymph node dissection for pure testicular seminoma is rare due to the chemosensitivity of this germ cell tumor. In this study we define the natural history of viable seminoma at post-chemotherapy retroperitoneal lymph node dissection., Materials and Methods: The Indiana University testis cancer database was queried from 1988 to 2011 to identify all patients with primary testicular or retroperitoneal pure seminoma and who were found to have pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. Clinical characteristics were reviewed and survival analysis was performed., Results: A total of 36 patients met the study inclusion criteria. All patients received standard first line cisplatin based chemotherapy and 17 received salvage chemotherapy. The decision to proceed to retroperitoneal lymph node dissection was based on enlarging retroperitoneal mass and/or positron emission positivity in the majority of cases. Seven patients had undergone previous retroperitoneal lymph node dissection. Additional surgical procedures were required in 19 patients to achieve a complete resection. The 5-year cancer specific survival rate was 54%. However, only 9 of 36 patients remained continuously free of disease and of these patients 4 received adjuvant chemotherapy. Mean time from post-chemotherapy retroperitoneal lymph node dissection to death was 6.9 months. Second line chemotherapy, reoperative retroperitoneal lymph node dissection and earlier era of treatment were associated with poorer cancer specific survival., Conclusions: A total of 36 patients with pure seminoma were found to have viable pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. While 5-year cancer specific survival was 54%, these surgeries are technically demanding and only a minority of patients achieves a durable cure from surgery alone., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)