Incidence Of Testicular Germ Cell Tumors Research Articles

Effect of 900 MHz radiofrequency electromagnetic radiation emitted from mobile phone on testicular immunity and the associated risk of testicular germ cell tumor

The emission of radiofrequency electromagnetic radiation (RF-EMR) from mobile phones has been implicated in causing inflammatory changes in the testis. Nevertheless, the direct association of these changes with the development of testicular germ cell tumors (TGCT) remains unclear. Therefore, we purposed to investigate the effect of RF-EMR exposure on inflammatory changes in the testis, cytokine gene expression levels, and the incidence of TGCT. Twenty male Wistar albino rats were randomly assigned to either the study or control groups. The study group was exposed to RF-EMR at 900 MHz, 26 V/m, and a specific absorption rate (SAR) of 0.14 W/kg for 4 h/day over 8 weeks. Histopathological analysis, vitality analysis using Annexin V, and real-time polymerase chain reaction for the analysis of interleukin 1 (IL-1), IL-4, IL-10, tumor necrosis factor-alpha, and interferon-gamma (IFN-γ) cytokine gene expressions were performed on the testicular tissue. The median testis weight (163.0 g [133.0 – 183.0] vs. 179.0 g [134.0 – 195.0], P = 0.012) and volume (0.95 cm3 [0.800 – 1.400] vs. 1.100 cm3 [1.050 – 1.500], P = 0.031) of the study group were significantly lower compared to the control group. The seminiferous tubule damage (P < 0.001) and interstitial edema (P = 0.042) were significantly higher in the study group. The tunica albuginea thickness was significantly reduced in the study group (P < 0.001). The fold changes in the expression levels of IL-4 and IFN-γ increased significantly in the study group. Our findings indicate that RF-EMR exposure causes structural, histopathological, and inflammatory toxic effects on the testis. The observed elevation in gene expression levels of IL-4 and IFN-γ cytokines following RF-EMR exposure suggests their potential role as regulators of TGCT initiation, thereby offering a viable potential therapeutic target in combination with current treatments. Nonetheless, future well-designed studies are necessary to validate our findings.

A Retrospective Analysis of 83 Patients with Testicular Mass Who Underwent Testis-Sparing Surgery: The Eurasian Uro-oncology Association Multicenter Study

Introduction: Herein, we analyzed the histopathological, oncological and functional outcomes of testis-sparing surgery (TSS) in patients with distinct risk for testicular cancer. Methods: This is a multicenter retrospective study on consecutive patients who underwent TSS. Patients were categorized in high- or low-risk testicular germ cell tumor (TGCT) according to the presence/absence of features compatible with testicular dysgenesis syndrome. Histology was categorized per size and risk groups. Results: TSS was performed in 83 patients (86 tumors) of them, 27 in the high-risk group. Fifty-nine patients had a non-tumoral contralateral testis present. Sixty masses and 26 masses were benign and TGCTs, respectively. No statistical differences were observed in mean age (30.9 ± 10.32 years), pathological tumor size (14.67 ± 6.7 mm) between risk groups or between benign and malignant tumors (p = 0.608). When categorized per risk groups, 22 (73.3%) and 4 (7.1%) of the TSS specimens were malignant in the high- and low-risk patient groups, respectively. Univariate analysis showed that the only independent variable significantly related to malignant outcome was previous history of TGCT. During a mean follow-up of 25.5 ± 22.7 months, no patient developed systemic disease. Local recurrence was detected in 5 patients and received radical orchiectomy. Postoperative testosterone levels remained normal in 88% of those patients with normal preoperative level. No erectile dysfunction was reported in patients with benign lesions. Conclusion: TSS is a safe and feasible approach with adequate cancer control, and preservation of sexual function is possible in 2/3 of patients harboring malignancy. Incidence of TGCT varies extremely between patients at high and low risk for TGCT requiring a careful consideration and counseling.

Testicular GERM cell tumors treatment outcome in a national cancer institution in Peru.

e17031 Background: Testicular germ cell tumor (TGCT) is the most common neoplasm in young men and the incidence has been increasing over the last few decades, especially among Hispanic men. Multidisciplinary management is associated with excellent oncological outcomes. Here, we describe the treatment outcome of TGCT patients treated in single institution in Peru. Methods: We conducted a retrospective study of TGCT treated at Instituto Nacional de Enfermedades Neoplasicas from 2016 to 2019. Clinical and pathological data were collected from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and compared with long-rank test. A level of p < 0.05 was considered significant. The statistical package SPSS v19 was used for the data analysis. Results: 221 patients were identified, 56% were non-seminomatous (NS) and 44% were seminomatous (S). Orchiectomy was performed in 94% of patients, only 6% underwent orchiectomy after chemotherapy. In both groups, the treatment regimens were: BEP (Bleomycin/Etoposide/cisplatin) 90%, Carboplatin 8.1% and EP (Etoposide/Cisplatin) 1.8%. 42 (21%) of patients receive rescue therapy, being the most frequent TIP (paclitaxel/ifosfamide/cisplatin). In NS patients, 5-year PFS was superior in good risk compared with poor risk (100% vs. 86%, p = 0.028) and for tumor markers level, S0 was superior to S3 (100% vs. 82%, p = 0.008). In S, 5-year PFS was no significant in any of groups of analysis. With a median follow-up of 57 months, OS in NS was 91%, 83% and 81% in 12, 36 and 60 months, respectively and OS in S was 96%, 87% and 87% in 12, 36 and 60 months, respectively. The analysis of 5-year OS according to clinical stage and risk stratification are shown in the Table 1. Only 2 patients received high-dose chemotherapy and still in complete response. Conclusions: Despite the high incidence of advanced TGCT, our patients had excellent survival results; being lower in those with CS III (both NS and S groups), poor risk and S3 for NS, and intermediate risk for S. Multidisciplinary management in a high volume institution is important for better outcomes in our patients. [Table: see text]

Chemotherapy‐induced toxicity in patients with testicular germ cell tumors: The impact of physical fitness and regular exercise

Testicular germ cell tumors (TGCTs) represent ∼95% of testicular malignancies and are the most common type of malignancy in young male adults. While the incidence of TGCTs has increased during the last decades, the advances in treatment, namely introducing cisplatin into the chemotherapy regimen, have made TGCTs highly curable with the 10-year survival rate exceeding 95%. However, in parallel with increased cure rates, survivors may experience acute and late adverse effects of treatment, which increase morbidity, reduce the quality of life, and can be potentially life-threatening. Chemotherapy-related toxicities include cardiovascular and metabolic diseases, secondary cancer, avascular necrosis, cognitive impairment, cancer-related fatigue, poor mental health-related quality of life, nephrotoxicity, hypogonadism, neurotoxicity, pulmonary toxicity, anxiety, and depression. These treatment-related adverse effects have emerged as important survivorship dilemmas in TGCT cancer survivors. Recently, regular physical exercise has increasingly attracted research and clinical attention as an adjunct therapy for cancer patients. Herein, we review the most common chemotherapy-related adverse effects in TGCT survivors and clinical relevance of exercise and increased cardio-respiratory fitness in modulating chemotherapy-related toxicity and quality of life in this population. Exercise has positive effects on a spectrum of physical and psychosocial outcomes during and after cancer treatment, and current guidelines on exercise prescription in chronic diseases define the recommended dose (volume and intensity) of regular exercise for cancer survivors, highlighting regular, sufficiently intensive physical activity as an essential part of patients' care.

Le cancer des organes génitaux externes de l’homme dans le département de l’Hérault: résultats de 30 ans d’enregistrement du registre des tumeurs de l’Hérault (1987–2016)

The objective of this study is to present the history of cancers of the external genital organs of male in Hérault using data from the Hérault tumor register (RTH) over a period of 30 years. Using the RTH database, we studied the development of testicular germ cell tumors (TGCT) and penile cancer (PC) over 30 years, from 1987 to 2016. We analyzed the incidence and mortality data for these tumors. We compared these results to French, European and global data. In 30 years of registration we have recorded 725 cases of TGCT and 175 cases of PC. The age standardized incidence rate (ASR) of TGCT has doubled between 1987 and 2016 (4.2 per 100,000 in 1987 and 9.3 per 100,000 in 2016). It was multiplied by 2.63 in the population of patients aged 30 to 44. There is a decrease of the mortality rate with a ASR of 0.8 deaths per 100,000 in 1987, and 0.4/100 000 in 2016. The PC incidence ASR was stable between 1987 and 2016 (0.4-0.9/100,000). Mortality is stable with a ASR between 0.1 and 0.3 deaths per 100,000 between 1987 and 2016. The incidence of TGCT has increased sharply in the Hérault over the past 30years, while a decrease in mortality has been observed. The proportion of seminomas is increasing; it has gone from 53% to 60% in 30years in the Hérault. The incidence and mortality of PC shows a stability in the Hérault over the past 30years.

Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer.

Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

Abstract 1203: Identification of 22 novel loci associated with susceptibility to testicular germ cell tumors

Abstract Background: Testicular germ cell tumors (TGCT) are the most common cancers in young men of European ancestry aged 20 to 39 years. The incidence of TGCT has doubled over the past 20 years, yet no robust environmental risk factors for disease have been identified. Although TGCTs are treatable by surgery, radiation, and platinum-based chemotherapy, multiple long-term toxicities of treatment often occur impacting morbidity and mortality. Due to their high heritability and homogenous cell of origin, TGCTs are well suited to genome-wide association methods. The Testicular Cancer Consortium (TECAC) has brought together the largest genome-wise association study (GWAS) study of TGCT to date. Methods: We conducted a GWAS of 5,602 cases and 5,006 controls aggregated from 12 locations in the US and Europe. Logistic regression models adjusted for study center and genomic ancestry. Genotypes were imputed against the Human Haplotype Reference Consortium. Meta-analysis was performed to combine GWAS results with summary statistics from five previously published TGCT studies, UK Biobank, deCODE Genetics, and an independent set of cases and controls, for a total of 10,156 cases and 179,683 controls. Biologic function of loci was explored using PAINTOR annotated with ATAC-seq data of four TGCT cell lines, SPATIAL-seq data of the NTERA2 TGCT cell-line, and publicly available data from ENCODE. Polygenic risk scores (PRS) were computed using subject-level data from the 5,602 cases and 5,006 controls, and effect sizes of the novel hits derived from the meta-analysis. Results: 22 novel and 45 previously reported loci associated with TGCT surpassed genome-wide significance (p < 5e-08). We discovered additional markers in known susceptibility loci and identified novel regions associated with germ cell development and sex determination (e.g., BCL11, AR), immune function (e.g., TNXB, ITIH5), and for the first time identified genes associated with kinetochore activity (e.g., PPP2R5A, ANAPC2). All identified risk SNPs to date account for 42.3% of heritability. Men in the highest 1% of PRS had over a 15-fold increased risk of TGCT compared to those at the median PRS, and PRS overall had an AUC of 74.29%. Conclusions: Results from our TGCT meta-analysis continue to provide insights into biological pathways affecting germ cell specification, expression, and epigenetic reprogramming, and sex determination. Our results also uniquely place TGCT as the only cancer type in which inherited variants implicating kinetochore activity, critical for chromosomal segregation, have been identified. Citation Format: John Pluta, Louisa Pyle, Timothy Bishop, Javier Benitez, Victoria Cortessis, Alberto Ferlin, Jourik Gietema, Mark Greene, Thomas Grotmol, Ramneek Gupta, Robert Hamilton, Michelle Hildebrandt, Lambertus Kiemeney, Davor Lessel, Thorunn Rafnar, Lorenzo Richiardi, Rolf Skotheim, Clare Turnbull, Fredrik Wiklund, Tongzhang Zheng, Ewa Rajpert- De Meyts, Stephen Schwartz, Katherine McGlynn, Peter Kanetsky, Katherine Nathanson. Identification of 22 novel loci associated with susceptibility to testicular germ cell tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1203.

Increasing Incidence of Testicular Germ Cell Tumors among Racial/Ethnic Minorities in the United States

The incidence of testicular germ cell tumors (TGCT) has been rising in the United States and is notably higher among white men. Previously, our group reported that rates were rising among Hispanic men in certain areas. This study sought to determine whether the patterns noted in our prior publication remained evident in more recent years and to determine whether any new patterns have emerged. Data from 51 U.S. cancer registries were examined. Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region. Annual percent changes (APC) were estimated, and joinpoint models were fit. Differences in regional incidence were examined using the Wald test. During the time period 2001 to 2016, 126,575 TGCTs were recorded. TGCT incidence was highest among non-Hispanic whites (NHW; 6.63/100,000), followed by Hispanics (4.20), American Indian/Alaska Natives (AI/AN; 3.27), Asian/Pacific Islanders (A/PI; 1.72), and non-Hispanic blacks (NHB; 1.27). TGCT incidence increased significantly among all men; the greatest increase was experienced by A/PIs (APC: 2.47), followed in order by Hispanics (2.10), AI/ANs (1.71), NHBs (1.28), and NHWs (0.41). Significant differences in rates by region were seen for all men except NHBs, with the highest rates among Hispanics (5.38/100,000), AI/ANs (4.47), and A/PIs (2.37) found in the West, and among NHWs (7.60) and NHBs (1.51) found in the Northeast. Although TGCT incidence remained highest among NHWs between 2001 and 2016, the greatest increase was experienced by A/PI men. Rising rates of TGCTs among men of all racial/ethnic backgrounds in the United States suggest that future attention is warranted.

Testicular cancer in Hispanics: incidence of subtypes over time according to neighborhood sociodemographic factors in California.

Hispanic men in the USA experience the second-highest incidence rate of testicular germ cell tumors (TGCTs), behind non-Hispanic (NH) White men, and have experienced steep increases in TGCT in recent decades. It is unknown whether increases in incidence differ according to neighborhood sociodemographic factors. We conducted a population-based study of n = 3759 Hispanic and n = 8469 NH White men (n = 12,228 total) diagnosed with TGCT in California during the three most recent pericensal periods. We calculated incidence rates according to neighborhood socioeconomic status (nSES) and among Hispanics, according to ethnic enclave. We calculated incidence rate ratios to compare rates across nSES and ethnic enclave and to examine changes in rates over pericensal time periods according to these neighborhood factors for major histologic types (i.e., seminoma and nonseminoma). Hispanic men residing in high SES, compared to low SES, neighborhoods had greater incidence of seminoma and nonseminoma testicular cancer across pericensal periods, as did Hispanic men in low enclave (less ethnic), compared to high enclave, neighborhoods. Between the periods 1998-2002 and 2008-2012, Hispanic men residing in low SES neighborhoods experienced a 39% increased incidence of seminoma, while those residing in low and middle SES neighborhoods experienced 87% and 48% increased incidence of nonseminoma, respectively. While TGCT incidence has increased among all Hispanic men, incidence increases appear to be driven disproportionately by those residing in lower SES and lower enclave neighborhoods, particularly for nonseminoma.

MP11-15 INCIDENCE OF METACHRONOUS CONTRALATERAL TESTICULAR CANCER AND ASSOCIATION WITH CHEMOTHERAPY

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer I (MP11)1 Apr 2020MP11-15 INCIDENCE OF METACHRONOUS CONTRALATERAL TESTICULAR CANCER AND ASSOCIATION WITH CHEMOTHERAPY Joost Blok*, Harmke Groot, Ronald De Wit, Jourik Gietema, Gerard Groenewegen, Alfred Witjes, Hetty Van den Berg, Jacqueline Tromp, Peter De Brouwer, Tineke Smilde, Maureen Aarts, Janine Nuver, Ben Vanneste, Ruud Bosch, Simon Horenblas, Richard Meijer, and Michael Schaapveld Joost Blok*Joost Blok* More articles by this author , Harmke GrootHarmke Groot More articles by this author , Ronald De WitRonald De Wit More articles by this author , Jourik GietemaJourik Gietema More articles by this author , Gerard GroenewegenGerard Groenewegen More articles by this author , Alfred WitjesAlfred Witjes More articles by this author , Hetty Van den BergHetty Van den Berg More articles by this author , Jacqueline TrompJacqueline Tromp More articles by this author , Peter De BrouwerPeter De Brouwer More articles by this author , Tineke SmildeTineke Smilde More articles by this author , Maureen AartsMaureen Aarts More articles by this author , Janine NuverJanine Nuver More articles by this author , Ben VannesteBen Vanneste More articles by this author , Ruud BoschRuud Bosch More articles by this author , Simon HorenblasSimon Horenblas More articles by this author , Richard MeijerRichard Meijer More articles by this author , and Michael SchaapveldMichael Schaapveld More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000831.015AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a metachronous contralateral testicular germ cell tumor (CTGCT). It is unclear whether treatment with platinum-based chemotherapy is associated with the risk of CTGCT. The primary aim was to evaluate the incidence of CTGCT in a large population-based cohort. Secondary aims were to analyze whether CTGCT is associated with number of chemotherapy cycles or histology of the primary tumor. METHODS: The incidence of metachronous CTGCT (≥2 months after diagnosis of primary TGCT) was evaluated in a nationwide cohort including patients diagnosed with TGCT between 1989-2007. Institutional review board approval was obtained from all centers. Standardized incidence ratios (SIRs) were computed to compare the incidence of CTGCT with the incidence of TGCT in the general population. The cumulative incidence of CTGCT was estimated. The association between treatment with chemotherapy and risk of CTGCT was analyzed in a multivariate Cox-model. RESULTS: The cohort consisted of 4,755 patients (seminoma: n=2,612; 54.9%). Median age at diagnosis was 33 years (IQR 26-40). A total of 1,047 patients (22.0%) were treated with platinum-based chemotherapy for their primary TGCT. Median follow-up was 17.0 years (IQR 12.7-22.0). A CTGCT was diagnosed in 136 patients with a median interval of 6.1 years (range 0.8-19.7).The overall 20-year cumulative incidence was 3.4% (95% CI 2.8-4.0) and was higher after seminoma (4.0%; 95% CI 3.3-4.9), compared to NSGCT (2.6%; 95% CI 1.9-3.4). The incidence was highest in patients diagnosed with a seminoma before the age of 25 (8.7%; 95% CI 4.2-15.2). The cumulative incidence did not increase after 20 years of follow-up. The SIRs were for seminoma: 22.1 (95% CI 17.8-27.1), for NSGCT: 8.6 (95% CI 6.3-11.6) and for the entire cohort: 14.6 (95% CI 12.2-17.2). In multivariate analysis, the risk of developing a CTGCT decreased with age (HR 0.93; 95% CI 0.90-0.96), was lower after NSGCT (HR 0.58; 95% CI 0.35-0.96), and decreased with every additional cycle of chemotherapy (HR 0.74; 0.64-0.85). This corresponds to a 26% lower risk of CTGCT for every extra chemotherapy cycle. CONCLUSIONS: TGCT patients have a 15 times higher risk of developing a CTGCT, compared to the general population. Patients diagnosed with a seminoma before the age of 25 have the highest risk. Treatment with platinum-based chemotherapy shows a dose-dependent association with lower risk of CTGCT. Long-term self-examination is advised in all TGCT patients. Source of Funding: Dutch Cancer Society and Dutch Uro-Oncology Studygroup © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e141-e141 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joost Blok* More articles by this author Harmke Groot More articles by this author Ronald De Wit More articles by this author Jourik Gietema More articles by this author Gerard Groenewegen More articles by this author Alfred Witjes More articles by this author Hetty Van den Berg More articles by this author Jacqueline Tromp More articles by this author Peter De Brouwer More articles by this author Tineke Smilde More articles by this author Maureen Aarts More articles by this author Janine Nuver More articles by this author Ben Vanneste More articles by this author Ruud Bosch More articles by this author Simon Horenblas More articles by this author Richard Meijer More articles by this author Michael Schaapveld More articles by this author Expand All Advertisement PDF downloadLoading ...

Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014.

Testicular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1-1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends. To analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany. TGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert-Koch-Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non-seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend-analysis in order to evaluate age-adjusted incidence trends in Germany. Tests were two-sided with a level of significance of α=0.05. In total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non-seminoma. Maximum incidence of seminoma and non-seminoma was observed for age-group 38-40 years and 26-28 years, respectively. No second peak for the incidences of seminoma and non-seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age-adjusted incidence rates over the reviewed time period in both cohorts. In this study differences in reginal tumor incidence rates for seminoma and non-seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany. In this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non-seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.

Incidence of testicular tumor subtypes according to the updatedWHO classification, North Rhine-Westphalia, Germany, 2008-2013.

In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors. The aim of this study was to provide up-to-date population-based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification. We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine-Westphalia for the years 2008-2013. We used population counts to estimate age-standardized incidence rates per million person-years (EUROSTAT revised European Standard Population). The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non-seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non-seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age-standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person-years) and embryonal carcinoma plus teratoma (4.9 per million person-years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31years) than those that did not include seminoma (28years). Population-based incidence time trends for seminomatous and non-seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non-seminomatous TGCTs are examined.

Update on epidemiologic considerations and treatment trends in testicular cancer

We aim to give an overview of the epidemiology and treatment trends of testicular germ cell tumors (TGCTs), with an emphasis on recent trends. The incidence of TGCT appears to be increasing, particularly in developed countries, although the reasons are not well understood. There is evidence of racial differences in predisposition to TGCT, with white men having highest risk and men of African or Asian descent having lower risk. In the United States, the incidence of TGCT among Hispanics appears to be rising most quickly. A recent genomic analysis indicates there is no highly penetrant major TGCT susceptibility gene. Incorporation of multidisciplinary care has led to excellent long-term cure rates; however, access to care and insurance remains barriers in young men. Recent treatment trends have centered on maximizing oncologic outcomes while minimizing long-term morbidity. Emerging population-level data provide critical insight into the evolving demographics of TGCT, which may allow for elucidation of biologic and environmental determinants of TGCT. Further, identification of socioeconomic barriers to excellent clinical outcomes will allow for targeted interventions to patients with unique demographic and socioeconomic considerations. Treatment trend analyses suggest that the field is moving toward minimizing treatment-related morbidity.

Malignant testicular germ cell tumors in postpubertal individuals with androgen insensitivity: prevalence, pathology and relevance of single nucleotide polymorphism-based susceptibility profiling.

What is the prevalence of malignant testicular germ cell tumors (TGCT) and its precursors, (pre-) germ cell neoplasia in situ (GCNIS), in late teenagers and adults who have androgen insensitivity syndrome (AIS) and the impact of an individual's genetic susceptibility to development of TGCT? No GCNIS or TGCT was diagnosed, but pre-GCNIS was identified in 14 and 10% of complete and partial AIS patients, respectively, and was associated with a higher genetic susceptibility score (GSS), with special attention for KITLG (rs995030) and ATFZIP (rs2900333). Many adult women with AIS decline prophylactic gonadectomy, while data regarding the incidence, pathophysiology and outcomes of TGCT in postpubertal individuals with AIS are lacking. The relevance of genetic factors, such as single nucleotide polymorphisms (SNPs), in predisposing AIS individuals to TGCT is unknown. This multicenter collaborative study on prophylactically removed gonadal tissue was conducted in a pathology lab specialized in germ cell tumor biology. Material from 52 postpubertal individuals with molecularly confirmed AIS (97 gonadal samples) was included; the median age at surgery was 17.5 (14-54) years. Immunohistochemical studies and high-throughput profiling of 14 TGCT-associated SNPs were performed. The main outcome measures were the prevalence of pre-GCNIS, GCNIS and TGCT, and its correlation with a GSS, developed based on the results of recent genome-wide association studies. The earliest recognizable change preceding GCNIS, referred to as pre-GCNIS, was present in 14% of individuals with complete and 10% of those with partial AIS at a median age of 16 years. No GCNIS or invasive TGCT were found. The median GSS was significantly greater for those with, compared to those without, pre-GCNIS (P = 0.01), with an overlap between groups. Our data suggest important roles for risk alleles G at KITLG (rs995030) and C at ATFZIP (rs2900333), among the 14 studied TGCT-associated SNPs. N/A. A limited number of cases were included. Our data suggest that the prevalence of pre-GCNIS in individuals with AIS beyond puberty is around 15%. Genetic susceptibility likely contributes to pre-GCNIS development in AIS but factors related to malignant progression remain unclear. Although data in older patients remain scarce, malignant progression appears to be a rare event, although the natural history of the premalignant lesion remains unknown. Therefore, the practice of routine prophylactic gonadectomy in adults with AIS appears questionable and the patient's preference, after having been fully informed, should be decisive in this matter. This study was supported by research grants from the Research Foundation Flanders (FWO) (to M.C.), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq G0D6713N) (to B.B.M. and M.C.) and the European Society for Pediatric Endocrinology (ESPE), granted by Novo Nordisk AB (to J.K.). There are no competing interests.

Differences at Presentation and Treatment of Testicular Cancer in Hispanic Men: Institutional and National Hospital-based Analyses

To describe epidemiologic patterns, stage at presentation, histology, and treatment differences associated with Hispanic men diagnosed with testicular germ cell tumor (TGCT). Hispanics are the fastest growing demographic in the United States and reports suggest that the incidence of TGCT is rising most rapidly in this demographic, yet little is known about TGCTs in Hispanic patients. We compared patient factors, tumor characteristics, treatment patterns, and outcomes of non-Hispanic white (NHW) vs Hispanic patients at our own institution in North Texas from 2010 to 2016. The findings were corroborated by analyzing the National Cancer Database testicular cancer registry from 2004 to 2014. We identified 154 patients with TGCT at our institution, of which 89 were NHW (56.0%) and 65 were Hispanic (40.9%). A review of the National Cancer Database identified 49,607 NHW patients (81.5%) and 6724 Hispanic patients (11.0%) diagnosed with TGCT. At presentation, Hispanic patients were approximately 5 years younger than NHW patients, delay seeking care for testicular cancer, were more likely to have nonseminomatous histology, had a larger tumor size, and had a higher disease burden at presentation. Additionally, we identified differences in treatment patterns at the national level. Differences in outcomes and treatment patterns of Hispanic and NHW patients with TGCT may represent underlying socioeconomic issues and access to care; however, discrepancies in age of onset and histology of TGCT between Hispanic and NHW patients may signify differences in tumor biology or risk factors. We suggest that this possibility be explored further as we embark upon the genomic classification of TGCT.

Future of testicular germ cell tumor incidence in the United States: Forecast through 2026.

Testicular germ cell tumors (TGCTs) are rare tumors in the general population but are the most commonly occurring malignancy among males between ages 15 and 44 years in the United States (US). Although non-Hispanic whites (NHWs) have the highest incidence in the US, rates among Hispanics have increased the most in recent years. To forecast what these incidence rates may be in the future, an analysis of TGCT incidence in the Surveillance, Epidemiology, and End Results program and the National Program of Cancer Registries was conducted. TGCT incidence data among males ages 15 to 59 years for the years 1999 to 2012 were obtained from 39 US cancer registries. Incidence rates through 2026 were forecast using age-period-cohort models stratified by race/ethnicity, histology (seminoma, nonseminoma), and age. Between 1999 and 2012, TGCT incidence rates, both overall and by histology, were highest among NHWs, followed by Hispanics, Asian/Pacific Islanders, and non-Hispanic blacks. Between 2013 and 2026, rates among Hispanics were forecast to increase annually by 3.96% (95% confidence interval, 3.88%-4.03%), resulting in the highest rate of increase of any racial/ethnic group. By 2026, the highest TGCT rates in the US will be among Hispanics because of increases in both seminomas and nonseminomas. Rates among NHWs will slightly increase, whereas rates among other groups will slightly decrease. By 2026, Hispanics will have the highest rate of TGCT of any racial/ethnic group in the US because of the rising incidence among recent birth cohorts. Reasons for the increase in younger Hispanics merit further exploration. Cancer 2017;123:2320-2328. © 2017 American Cancer Society.

Bilateral Testicular Germ Cell Tumors in the Era of Multimodal Therapy

To characterize the incidence, presentation, management, and relapse of a large population of bilateral testicular germ cell tumors (TGCT) from a single institution. We identified bilateral TGCT diagnosed between January 1989 and February 2014. We categorized synchronous and metachronous TGCT, noting time between first and second TGCT, histology (seminoma vs nonseminoma [NSGCT]), stage, and treatments. Kaplan-Meier survival estimates characterized relapse. Of 5132 patients with TGCT, 128 (2.5%) had bilateral TGCT. Bilateral TGCT increased over time-1.7% in 1989-1994 up to 3.8% in 2010 to February 2014. The 35 (27%) synchronous cases of TGCT had 20 (57%) concordant seminoma, 5 (14%) concordant NSGCT, and 10 (29%) discordant NSGCT. The 93 (73%) metachronous cases had median time interval to second TGCT of 73 months (range: 5 months-28.6 years). Compared with first TGCT, 39 (42%) had discordant histology, 29 (31%) had concordant seminoma, and 25 (27%) had concordant NSGCT. Stage at first tumor was statistically similar to second TGCT (second stage I, II, II in 69%, 22%, 10%). Increasing duration between first and second TGCT was not associated with higher stage (II or III) at second TGCT (P = .09). Treatment at first tumor was not associated with stage at second tumor. Relapse following bilateral diagnosis was 16.8% (95% confidence interval 10.5%-26.2%) at 5 years. Incidence of bilateral TGCT increased with >25% of metachronous TGCT presenting ≥10 years after first TGCT; possible causes include increased survivorship and referral bias. Stage was statistically similar at first and second tumor; stage at second tumor was not associated with time interval between tumors or prior treatment modality at first tumor.

Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.

Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1-23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6). Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies.

Incidence of testicular germ cell tumors among US men by census region.

The incidence of testicular germ cell tumors (TGCTs) in the United States is notably higher among white men versus other men. Previously, however, it was reported that rates were rising among Hispanics in certain areas. To determine whether this finding was evident in a wider area of the United States, data from 39 US cancer registries were examined. Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region for the period of 1998-2011. Annual percentage changes (APCs) were estimated, and joinpoint models were fit. Differences in incidence by region were examined with the Wald test. From 1998 to 2011, 88,993 TGCTs were recorded. The TGCT incidence was highest among non-Hispanic whites (6.57 per 100,000), who were followed by Hispanics (3.88), American Indians/Alaska Natives (2.88), Asians/Pacific Islanders (A/PIs; 1.60), and non-Hispanic blacks (1.20). The incidence significantly increased among Hispanics (APC, 2.31; P < .0001), with rates rising in all regions except the South. Rates rose slightly among non-Hispanic whites (APC, 0.51; P = .0076). Significant differences in rates by region were seen for Hispanics (P = .0001), non-Hispanic whites (P < .0001), and A/PIs (P < .0001), with the highest rates among Hispanics in the West and with the highest rates among non-Hispanic whites and A/PIs in the Northeast. Although the incidence of TGCTs remained highest among non-Hispanic whites between 1998 and 2011, the greatest increase was experienced by Hispanics. Rising rates of TGCTs among Hispanics in the United States suggest that future attention is warranted. Reasons for the increase may include variability in birthplace, changing exposures, genetic susceptibility, and the length of US residence.

Testicular Cancer, Version 2.2015.

Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups--pure seminoma and nonseminoma--which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.