Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012).

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Testicular cancer follow-up costs in Germany from 2000 to 2015.

PURPOSE: Advances in testicular cancer screening and therapy increased 10-year survival to 97% despite a rising incidence; eventually expanding the population of survivors requiring follow-up. We analyzed 10-year follow-up costs after testicular cancer treatment in Germany during 2000, 2008, and 2015. METHODS: Testicular cancer follow-up guidelines were extracted from the European Association of Urology. Per patient costs were estimated with a micro-costing approach considering direct and indirect medical expenses derived from expert interviews, literature research, and official scales of tariffs. Three perspectives covering costs for patients, providers, and insurers were included to estimate societal costs. Cost progression was compared across cancer histology, stage, stakeholders, resource use, and follow-up years. RESULTS: Mean 10-year follow-up costs per patient for stage I seminomatous germ-cell tumors (SGCT) on surveillance declined from EUR 11,995 in 2000 to EUR 4,430 in 2015 (p < 0.001). Advanced SGCT spending shrank from EUR 13,866 to EUR 9,724 (p < 0.001). In contrast, expenditure for stage II SGCT increased from EUR 7,159 to EUR 9,724 (p < 0.001). While insurers covered 32% of costs in 2000, only 13% of costs were reimbursed in 2015 (p < 0.001). 70% of SGCT follow-up resources were consumed by medical imaging (x-ray, CT, ultrasound, FDG-PET). Spending was unevenly distributed across follow-up years (years 1-2: 50%, years 3-5: 39%, years 5-10: 11%). CONCLUSIONS: The increasing prevalence of testicular cancer survivors caused German statutory insurers to cut per patient cost by up to 80% by budgeting services and decreasing reimbursement rates. The economic burden was gradually redistributed to patients and providers.

Evidence-based benchmarks for use of cancer surgery in high-income countries: a population-based analysis.

BACKGROUND: Estimating a population-level benchmark rate for use of surgery in the management of cancer helps to identify treatment gaps, estimate the survival impact of such gaps, and benchmark the workforce and other resources, including budgets, required to meet service needs. A population-based benchmark for use of surgery in high-income settings to inform policy makers and service provision has not been developed but was recommended by the Lancet Oncology Commission on Global Cancer Surgery. We aimed to develop and validate a cancer surgery benchmarking model. METHODS: We examined the latest clinical guidelines from high-income countries (Australia, the UK, the EU, the USA, and Canada) and mapped surgical treatment pathways for 30 malignant cancer sites (19 individual sites and 11 grouped as other cancers) that were notifiable in Australia in 2014, broadly reflecting contemporary high-income models of care. The optimal use of surgery was considered as an indication for surgery where surgery is the treatment of choice for a given clinical scenario. Population-based epidemiological data, such as cancer stage, tumour characteristics, and fitness for surgery, were derived from Australia and other similar high-income settings for 2017. The probabilities across the clinical pathways of each cancer were multiplied and added together to estimate the population-level benchmark rates of cancer surgery, and further validated with the comparisons of observed rates of cancer surgery in the South Western Sydney Local Health District in 2006-12. Univariable and multivariable sensitivity analyses were done to explore uncertainty around model inputs, with mean (95% CI) benchmark surgery rates estimated on the basis of 10 000 Monte Carlo simulations. FINDINGS: Surgical treatment was indicated in 58% (95% CI 57-59) of newly diagnosed patients with cancer in Australia in 2014 at least once during the course of their treatment, but varied by site from 23% (17-27) for prostate cancer to 99% (96-99) for testicular cancer. Observed cancer surgery rates in South Western Sydney were comparable to the benchmarks for most cancers, but were higher for some cancers, such as prostate (absolute increase of 29%) and lower for others, such as lung (-14%). INTERPRETATION: The model provides a new template for high-income and emerging economies to rationally plan and assess their cancer surgery provision. There are differences in modelled versus observed surgery rates for some cancers, requiring more in-depth analysis of the observed differences. FUNDING: University of New South Wales Scientia Scholarship, UK Research and Innovation-Global Challenges Research Fund.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

National burden of cancer in Italy, 1990-2017: a systematic analysis for the global burden of disease study 2017.

We monitored the burden of cancer in Italy and its trends over the last three decades, providing estimates of cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs), for cancer overall and 30 cancer sites using data from the Global Burden of Disease study 2017. An overview of mortality trends between 1990 and 2017 was also provided. In 2017, there were 254,336 new cancer cases in men and 214,994 in women, corresponding to an age-standardized incidence rate (ASIR) of 438 and 330/100,000, respectively. Between 1990 and 2017, incident cancer cases, and, to a lesser extent, ASIRs significantly increased overall and for almost all cancer sites, but ASIRs significantly declined for lung and other tobacco-related neoplasms. In 2017, there were 101,659 cancer deaths in men (age-standardized death rate, ASDR, 158.5/100,000) and 78,918 in women (ASDR 93.9/100,000). Cancer deaths significantly increased between 1990 and 2017 (+ 18%), but ASDR significantly decreased (- 28%). Deaths significantly increased for many cancer sites, but decreased for stomach, esophageal, laryngeal, Hodgkin lymphoma, and testicular cancer. ASDRs significantly decreased for most neoplasms, with the main exceptions of cancer of the pancreas and uterus, and multiple myeloma. In 2017, cancer caused 3,204,000 DALYs. Between 1990 and 2017, DALYs and age-standardized DALY rates significantly declined (-3.4% and -33%, respectively). Age-standardized mortality rates in Italy showed favorable patterns over the last few decades. However, the absolute number of cancer cases and, to a lower extent, of cancer deaths increased likely due to the progressive ageing of the population, this calling for a continuous effort in cancer prevention, early diagnosis, and treatment.

Race, ethnicity, and socioeconomic differences in incidence of pediatric embryonal tumors in the United States.

BACKGROUND: The etiology of childhood cancers and its social patterning remains largely unknown. Accounting for socioeconomic status (SES) when exploring the association between race/ethnicity and cancer incidence is necessary to better understand such etiology. We aimed to investigate differences in the incidence of embryonal tumors (ETs) by SES and race/ethnicity in the United States using population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program. PROCEDURE: Children with ETs aged 0-19 years diagnosed between 2000 and 2015 were ascertained from the census tract-level SEER database. SES was measured using a tract-level composite index. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) by SES quintile and race/ethnicity were estimated using multivariable Poisson regression models. RESULTS: The majority of tumors had lower incidence among nonwhite children compared with non-Hispanic (NH) white children, after controlling for SES. NH blacks had a higher incidence of Wilms tumor than NH whites (IRR: 1.26; 95% CI, 1.13-1.39). There was an increasing linear trend (P = 0.0001) across increasing SES quintile for embryonal rhabdomyosarcoma after controlling for race/ethnicity. Effect modification by race/ethnicity of the relationship between SES and tumor incidence was observed for several groups. Hispanics had a significant, linear trend (P = 0.0005) in the incidence of Wilms tumor, while Asian/Pacific Islanders experienced a significant inverse trend (P = 0.0002). CONCLUSIONS: Results from this study suggest differences in the incidence of several ETs by race/ethnicity and that these differences may be modified by SES. Investigation of potential risk factors that are socially patterned is warranted.

Racial and Ethnic Disparities in the Incidence of Pediatric Extracranial Embryonal Tumors.

Background: Few studies have comparatively assessed differences in the incidence of childhood cancer by race and ethnicity that could inform etiologic research. We aimed to identify disparities in the incidence of pediatric extracranial embryonal tumors by race and ethnicity in the United States using a population-based cancer registry. Methods: Cases of extracranial embryonal tumors among children age 0 to 19 years diagnosed between 2000 and 2010 were retrieved from the Surveillance, Epidemiology, and End Results Program 18 (n = 8188). Age-standardized incidence rates and incidence rate ratios (IRRs) were obtained by race/ethnicity. Whites were the reference group. The percentage of families living below the poverty line by county was used to stratify by socioeconomic status (SES). Results: All minority groups had a lower incidence of neuroblastoma (Hispanics: IRR = 0.53, 95% confidence interval [CI] = 0.47 to 0.59; blacks: IRR = 0.70, 95% CI = 0.61 to 0.81; Native-Hawaiian/Asian-Pacific-Islander (API): IRR = 0.56, 95% CI = 0.46 to 0.67; and American Indian/Alaska Native (AI/AN): IRR = 0.28, 95% CI = 0.15 to 0.48) while Hispanics had a higher incidence of retinoblastoma (IRR = 1.26, 95% CI = 1.07 to 1.48). Incidence of nephroblastoma was lower among Hispanics (IRR = 0.80, 95% CI = 0.71 to 0.91) and API (IRR = 0.43, 95% CI = 0.33 to 0.56) while equivalent for blacks. Similarly, incidence of rhabdomyosarcoma was low among Hispanics (IRR = 0.85, 95% CI = 0.74 to 0.98) and API (IRR = 0.61, 95% CI = 0.47 to 0.79) while equivalent for blacks. However, incidence of hepatoblastoma was low among blacks (IRR = 0.44, 95% CI = 0.28 to 0.68) while equivalent for Hispanics and API. Incidence of germ cell tumors was higher among Hispanics (IRR = 1.30, 95% CI = 1.19 to 1.42) and lower among blacks (IRR = 0.52, 95% CI = 0.44 to 0.61) and API (IRR = 0.79, 95% CI = 0.67 to 0.93). No effect modification by SES was observed. Conclusions: Unique incidence patterns of childhood extracranial embryonal tumors exist by race and ethnicity in the United States. The interplay between race/ethnicity and genetics, epigenetics, and gene-environment interactions in the causation of these cancers deserves further investigation.

Small Numbers, Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand.

PURPOSE: This study was undertaken to determine cancer survival and describe the unique spectrum of cancers diagnosed among New Zealand's adolescents and young adult (AYA) population. METHODS: Registrations for 1606 15-24 year olds diagnosed with a new primary malignant tumor between 2000 and 2009 were obtained from the New Zealand Cancer Registry and classified according to AYA diagnostic group and subgroup, age, sex, and prioritized ethnicity. Age-standardized incidence rates (IRs) per million person years and 5-year relative survival ratios were calculated. RESULTS: Cancer incidence was 228.6 per million for adolescents aged 15-19 years and 325.7 per million for young adults aged 20-24 years. Overall IRs were consistent across all ethnic groups but there were unique ethnic differences by tumor group including a higher incidence of bone tumors, carcinoma of the gastrointestinal tract, and gonadal germ cell tumors among Maori, a higher incidence of leukemia among Pacific peoples, and a higher incidence of melanoma among non-Maori/non-Pacific peoples. Five-year relative survival for adolescents (75.1%) and AYA overall (80.6%) appeared poorer than had been achieved in other high-income countries. Maori (69.5%) and Pacific (71.3%) AYA had lower 5-year survival compared to non-Maori/non-Pacific peoples (84.2%). CONCLUSION: The survival disparities observed require further investigation to identify and address the causes of these inferior outcomes. The newly established AYA Cancer Network Aotearoa has been tasked with improving cancer survival and care and ensuring equality of access for New Zealand AYAs with cancer.

A novel rapid access testicular cancer clinic: prospective evaluation after one year.

BACKGROUND: Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). AIMS: To present our experience after 12 months. METHODS: All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. RESULTS: Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. CONCLUSION: The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

Socioeconomic patterning in the incidence and survival of teenage and young adult men aged between 15 and 24 years diagnosed with non-seminoma testicular cancer in northern england.

PURPOSE: Previous research from developed countries has shown a marked increase in the incidence of testicular cancer in the past 50 years. This has also been demonstrated in northern England, along with improving 5-year survival. The present study aims to determine if socioeconomic factors may play a role in both etiology and survival from non-seminoma testicular cancer. MATERIALS AND METHODS: We extracted all 214 cases of non-seminoma testicular cancer diagnosed in teenage and young adult men aged between 15 and 24 years during 1968 to 2006 from the Northern Region Young Persons' Malignant Disease Registry, which is a population-based specialist regional registry. Negative binomial regression was used to examine the relationship between incidence and both the Townsend deprivation score (and component variables) and small-area population density. Cox regression was used to analyze the relationship between survival and both deprivation and population density. RESULTS: Decreased incidence was associated with living in areas of higher household overcrowding for young adults aged between 20 and 24 years (relative risk per 1% increase in household overcrowding = 0.79; 95% CI: 0.66-0.94) but no association was detected for young people aged between 15 and 19 years. Community-level household unemployment was associated with worse survival (hazard ratio per 1% increase in household unemployment = 1.04; 95% CI: 1.00-1.08). CONCLUSIONS: This study has shown that increased risk of non-seminoma testicular cancer in teenage and young adult men may be associated with some aspect of more advantaged living. In contrast, greater deprivation is linked with worse survival prospects. The study was ecological by design and so these area-based results may not necessarily apply to individuals.

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

INTRODUCTION: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. PURPOSE: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). METHODS: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. RESULTS: The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. CONCLUSIONS: EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.

Disparities in stage at diagnosis among adults with testicular germ cell tumors in the National Cancer Data Base.

BACKGROUND: Testicular germ cell tumors (TGCTs) are the most common malignancies among US men between the ages of 20 and 34. Five-year survival has increased since 1970s (95%), but remains below 75% for patients with late-stage disease. Few studies have examined the sociodemographic predictors of late-stage diagnosis, and none have examined the relationship between stage at diagnosis and health insurance among TGCTs. METHODS AND MATERIALS: A total of 48,151 men between the age of 15 and 64 years who were diagnosed with first primary invasive TGCTs from 1998 to 2008 were selected from the National Cancer Data Base. The effect of health insurance, race/ethnicity, ZIP code-based socioeconomic status, and other factors on late-stage diagnosis was examined using histology-stratified multivariate log binomial models to measure relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Overall, 6.6% and 21.2% of seminomas and nonseminomas were diagnosed at late stage, respectively. Uninsured men (seminomas: RR, 1.88, 95% CI, 1.65-2.13; nonseminomas: RR,1.42, 95% CI, 1.32-1.54), Medicaid-insured men (seminomas: RR, 2.99, 95% CI, 2.64-3.38; nonseminomas: RR 2.82, 95% CI, 2.48-3.22), and Medicare-insured men (seminomas: RR, 2.30, 95% CI, 1.91-2.77; nonseminomas: RR 2.02 95% CI, 1.67-2.44) were more likely to be diagnosed at late stage compared with privately insured men. Black men (nonseminomas: RR, 1.43, 95% CI, 1.25-1.64) and Hispanic men (seminomas: RR, 1.34, 95% CI, 1.16-1.55; nonseminomas: RR, 1.22, 95% CI, 1.12-1.33) were significantly more likely to be diagnosed at late stage. Lower socioeconomic status was associated with an increased risk of late-stage diagnosis among both seminomas and nonseminomas. CONCLUSIONS: Sociodemographic covariates, particularly health insurance, race/ethnicity, and socioeconomic status, were predictors of late-stage diagnosis. TGCTs are typically diagnosed among younger men who are less likely to have health insurance. Future efforts should aim to increase health insurance coverage and access to primary care, reduce barriers to care, and promote informed decision making for underserved populations.

Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe.

We provide updated estimates of survival, incidence, complete prevalence, and proportion cured for patients with testicular/paratesticular and extragonadal germ cell cancers in Europe, grouped according to the new list of cancer types developed by RARECARE. We collected data, archived in European cancer registries, with vital status information available to 31st December 2003. We analysed 26,000 cases of testicular, paratesticular and extragonadal germ cell cancers diagnosed 1995-2002, estimating that about 15,600 new testicular/paratesticular and 630 new extragonadal cancer cases occurred per year in EU27, with annual incidence rates of 31.5/1,000,000 and 1.27/1,000,000, respectively. Slightly more than 436,000 persons were alive at the beginning of 2008 with a diagnosis of testicular/paratesticular cancer, and about 17,000 with a diagnosis of extragonadal germ cell cancer. Five-year relative survival was 96% for testicular/paratesticular cancer and 71% for extragonadal germ cell cancer; the proportions cured were 95% and 69%, respectively. We found limited variation in survival between European regions except for non-seminomatous testicular cancer, for which five-year relative survival ranged from 86% in Eastern Europe to 96% in Northern Europe. Survival for all cancer types considered decreased with increasing age at diagnosis. Further investigation is required to establish the real reasons for the lower survival in Eastern Europe. Considering the high prevalence of these highly curable cancers, it is important to monitor patients long-term, so as to quantify treatment-related risks and develop treatments having limited impact on quality of life.

The incidence and management of metachronous testicular germ cell tumors in patients with extragonadal germ cell tumors.

OBJECTIVES: The optimal management of extragonadal germ cell tumor (EGGCT) and metachronous testicular germ cell tumor (MTGCT) has not been determined. PATIENTS AND METHODS: Fifty-one consecutive patients with EGGCT were identified. Testicular palpation or ultrasonography to rule out a primary testicular tumor was performed. Pretreatment testicular biopsies were not performed. The incidence and outcome of MTGCT, and the prognosis of EGGCT were evaluated. RESULTS: Twenty-five and 26 patients, respectively, had mediastinal and retroperitoneal EGGCT. Fourteen and 37 patients, respectively, had seminoma and nonseminoma. Five patients developed MTGCT in patients with retroperitoneal EGGCT. The median interval from the primary treatment for EGGCT to MTGCT diagnosis was 64 months (range 15-120). The cumulative risk of developing MTGCT was 8.3% at 6 y. Five patients underwent an orchiectomy and have survived in the 16-months median follow-up period (range 4-30). Among the patients with seminomatous and nonseminomatous EGGCT, the 5-year survival rate was 84.6% and 78.3%, respectively. Among the patients with retroperitoneal and mediastinal nonseminomatous EGGCT, the 5-year survival rate was 94.7% and 58.8%, respectively. CONCLUSIONS: The prognosis of EGGCT without testicular biopsies was sufficient. EGGCT patients, especially retroperitoneal EGGCT, need long-term follow-up for MTGCT.

A stratified genetic risk assessment for testicular cancer.

Three genome-wide association studies of testicular cancer have uncovered predisposition alleles in or near KITLG, BAK1, SPRY4, TERT, ATF7IP and DMRT1. We investigated whether testicular cancer-risk alleles can be utilized in the clinical setting. We employed the receiver operating characteristic curves for genetic risk models to measure the discriminatory power of a risk variant-based risk model, and found that the newly discovered variants provided a discriminatory power of 69.2%. This suggested that about 69.2% of the time, a randomly selected patient with testicular cancer had a higher estimated risk than the risk for a randomly selected control subject. Using a multiplicative model, we estimated that white men in the top 1% of genetic risk as defined by eight risk variants had a relative risk that was 10.5-fold greater than that for the general white male population. This risk differential does not appear to be clinically useful, given the relative rarity and highly curable nature of testicular germ cell tumour (TGCT). In the authors' view, a stratified genetic risk assessment strategy might be useful, theoretically, for men who also have independent clinical risk factors for testicular cancer. Several established TGCT risk factors, such as cryptorchidism (RR=4.8) and male infertility (SIR=2.8) might prove useful in that context, but we currently do not know whether these testicular cancer-risk loci are associated with, or independent of, such clinical risk factors. More research is required before we can utilize testicular cancer-risk loci for clinically meaningful risk prediction.

Laparoscopic retroperitoneal lymph node dissection for nonseminomatous germ-cell tumors: current status.

We review the published literature regarding the technical feasibility, oncologic outcomes, morbidity, and cost-effectiveness of laparoscopic retroperitoneal lymph node dissection (LRPLND). With proof that it is feasible, several centers have become expert in LRPLND and morbidity appears to be less than that of open RPLND. As the technique improves, it is likely that LRPLND will become equally if not more cost-effective than conventional RPLND. However, the oncologic outcomes, while on par with open RPLND series, are difficult to attribute to successful LRPLND alone when nearly all patients with positive lymph nodes received chemotherapy postoperatively. Although uncertainties exist, LRPLND holds much future promise.

[Structure, use, and risks of biomaterial repositories of embryonal tumors]. / Biomaterialbanken für embryonale Tumoren: Struktur, Nutzen und Risiken.

Availability of statistically sufficient numbers of tumor samples and other biomaterials in high quality together with corresponding clinical data is crucial for biomedical research. Tumor repositories from individual scientists are mostly not sufficient to satisfy these criteria, especially since pediatric tumors are rare. In 2000 three centralized tumor repositories (neuroblastoma in Cologne, nephroblastoma in Würzburg, hepatoblastoma, brain tumors in Bonn) have been established by the "German Competence Net Pediatric Oncology und Hematology". The aim was to collect biomaterial including tumor samples, normal tissue, and blood in high quality for research and diagnostic purposes at a central institution. Informed consent of the parents or patients is a prerequisite for scientific use of the samples and is requested by the therapy trial. The samples are collected according to accepted standards and shipped in the specially designed Tumorbox. The tumor repository organizes the distribution of the samples to the cooperating diagnostic laboratories. The number of collected tumor samples has increased over the years. In 2000, samples from 200 patients were collected while the patient number increased to 321 in 2005. Over the years the tumor repositories collected more than 7,150 samples (fresh frozen tumor, fresh frozen normal tissue, and blood). Through links with clinical trial databases the samples can be connected with clinical data. 12 of 14 applications for tumor material to be used in specific scientific projects have been approved by an independent supervisory board. The establishment of central tumor repositories represents a major step for biomedical research activities and quality control in pediatric oncology.

Early detection of relapse after treatment for metastatic germ cell tumour of the testis: an exercise in medical audit.

The relapse patterns of 29 patients who recurred following treatment for metastatic germ cell tumours of the testis (seminoma n = 7, non-seminomatous germ cell tumour n = 22) have been analysed and the relative effectiveness of clinical follow-up and routine investigations in detecting relapse at an early stage have been examined. The analysis shows that routine estimation of the serum tumour markers human chorionic gonadotrophin and alpha-foetoprotein (HCG and AFP) is the single most important follow-up procedure. This is so, even in patients who were previously marker negative; it was the first indicator of relapse in 55% of the patients. Regular clinical examination and chest radiograph in asymptomatic patients was of little value. Chest radiograph gave the first evidence of relapse in only 2 cases (7%). The optimum frequency for follow-up computed tomographic scanning of the chest and abdomen remains debatable. In this series, it was the first abnormal investigation in 7 patients (24%) and proved to be particularly important in patients who had residual radiological abnormalities at the end of initial therapy. Cost analysis shows that intensive follow-up produces a total expenditure on investigations of approximately 4,500 pounds per relapse detected. Regular computed tomographic scanning is especially demanding on resources and costs approximately 12,880 pounds per relapse detected if the recommended protocol is followed.