Cardiovascular Risk Factors and Disease After Male Germ Cell Cancer.

PURPOSE: To analyze the risk of cardiovascular disease (CVD) after treatment of male germ cell cancer (GCC). METHODS: Clinical data were extracted from the Danish Testicular Cancer database. For each patient, 10 men matched on date of birth were identified in the Danish normal population by risk-set sampling. Cardiovascular risk factors, CVD, and associated deaths were identified in Danish registries. The association between treatment and outcomes was analyzed by separate Cox models for each outcome. Cancer treatment was included as a time-varying covariate. RESULTS: We included 5,185 patients with GCC and 51,850 men in the normal population. Median follow-up was 15.8 years. Treatment with bleomycin-etoposide-cisplatin (BEP; n = 1,819) was associated with increased risks of hypertension and hypercholesterolemia. Hazard ratios (HRs) of CVD < 1 year after initiation of BEP treatment were as follows: myocardial infarction (HR, 6.3; 95% CI, 2.9 to 13.9), cerebrovascular accident (HR, 6.0; 95% CI, 2.6 to 14.1), and venous thromboembolism (HR, 24.7; 95% CI, 14.0 to 43.6). One year after BEP treatment, the risk of CVD decreased to normal levels, but after 10 years, increasing risks were found for myocardial infarction (HR, 1.4; 95% CI, 1.0 to 2.0) and cardiovascular death (HR, 1.6; 95% CI, 1.0 to 2.5). Radiotherapy (n = 780) increased the risk of diabetes at long-term follow-up (HR, 1.4; 95% CI, 1.0 to 2.0) but not that of other outcomes. With surveillance (n = 3,332), cardiovascular risk factors, CVD, and cardiovascular death data were comparable to that of the normal population. CONCLUSION: Treatment with BEP was associated with highly increased risks of CVD < 1 year after treatment start and mildly increased risks after 10 years of follow-up. Radiotherapy increased the risk of diabetes but not incident CVD. The risk of CVD in patients followed in a surveillance program was comparable to that of the normal population.

Understanding Differences in Cancer Survival between Populations: A New Approach and Application to Breast Cancer Survival Differentials between Danish Regions.

Large variations in cancer survival have been recorded between populations, e.g., between countries or between regions in a country. To understand the determinants of cancer survival differentials between populations, researchers have often applied regression analysis. We here propose the use of a non-parametric decomposition method to quantify the exact contribution of specific components to the absolute difference in cancer survival between two populations. Survival differences are here decomposed into the contributions of differences in stage at diagnosis, population age structure, and stage-and-age-specific survival. We demonstrate the method with the example of differences in one-year and five-year breast cancer survival between Denmark's five regions. Differences in stage at diagnosis explained 45% and 27%, respectively, of the one- and five-year survival differences between Zealand and Central Denmark for patients diagnosed between 2008 and 2010. We find that the introduced decomposition method provides a powerful complementary analysis and has several advantages compared with regression models: No structural or distributional assumptions are required; aggregated data can be used; and the use of absolute differences allows quantification of the survival that could be gained by improving, for example, stage at diagnosis relative to a reference population, thus feeding directly into health policy evaluation.

Cohort Profile: The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE).

The cohort was set up in order to analyze late effects in long-term testicular cancer survivors (TCS) and to contribute to the design of future follow-up programs addressing and potentially preventing late effects. Data for this cross-sectional study were collected between January 1, 2014, and December 31, 2016, among living Danish TCS and 60% agreed to participate in the cohort (N = 2,572). Mean time since testicular cancer (TC) diagnosis was 18 years (range 7-33) and mean age of participants was 53 years (range 25-95). Data consist of results of a questionnaire with patient reported outcomes which covers a broad range of items on late-effects. The study also included data obtained through linkages to Danish registries, a biobank, and clinical data from hospital files and pathology reports originating from the Danish Testicular Cancer Database (DaTeCa). The treatment during the observation period has been nearly the same for all stages of TC and is in agreement with today's standard treatment, this allows for interesting analysis with a wide timespan. We have extensive data on non-responders and are able to validate our study findings. Data from a Danish reference population (N = 162,283) allow us to compare our findings with a Danish background population. The cohort can easily be extended to access more outcomes, or include new TCS. A limitation of the present study is the cross-sectional design and despite the large sample size, The Danish Testicular Cancer Late Treatment Effects Cohort (DaTeCa-LATE) lacks statistical power to study very rare late effects. Since it was voluntary to participate in the study we have some selection bias, for instance, we lack responders who were not in a paired relationship, but we would still argue that this cohort of TCSs is representative for TCSs in Denmark. COLLABORATION AND DATA ACCESS: Researches interested in collaboration with the DaTeCa-LATE study group please contact Professor Gedske Daugaard kirsten.gedske.daugaard@regionh.dk.

The Danish Testicular Cancer database.

AIM: The nationwide Danish Testicular Cancer database consists of a retrospective research database (DaTeCa database) and a prospective clinical database (Danish Multidisciplinary Cancer Group [DMCG] DaTeCa database). The aim is to improve the quality of care for patients with testicular cancer (TC) in Denmark, that is, by identifying risk factors for relapse, toxicity related to treatment, and focusing on late effects. STUDY POPULATION: All Danish male patients with a histologically verified germ cell cancer diagnosis in the Danish Pathology Registry are included in the DaTeCa databases. Data collection has been performed from 1984 to 2007 and from 2013 onward, respectively. MAIN VARIABLES AND DESCRIPTIVE DATA: The retrospective DaTeCa database contains detailed information with more than 300 variables related to histology, stage, treatment, relapses, pathology, tumor markers, kidney function, lung function, etc. A questionnaire related to late effects has been conducted, which includes questions regarding social relationships, life situation, general health status, family background, diseases, symptoms, use of medication, marital status, psychosocial issues, fertility, and sexuality. TC survivors alive on October 2014 were invited to fill in this questionnaire including 160 validated questions. Collection of questionnaires is still ongoing. A biobank including blood/sputum samples for future genetic analyses has been established. Both samples related to DaTeCa and DMCG DaTeCa database are included. The prospective DMCG DaTeCa database includes variables regarding histology, stage, prognostic group, and treatment. CONCLUSION: The DMCG DaTeCa database has existed since 2013 and is a young clinical database. It is necessary to extend the data collection in the prospective database in order to answer quality-related questions. Data from the retrospective database will be added to the prospective data. This will result in a large and very comprehensive database for future studies on TC patients.

Late Relapses in Stage I Testicular Cancer Patients on Surveillance.

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.

Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort.

PURPOSE: To describe treatment results in a large cohort with stage I nonseminoma germ cell cancer (NSGCC) treated in a surveillance program. PATIENTS AND METHODS: From January 1, 1984, to December 31, 2007, 1,226 patients with stage I NSGCC, including high-risk patients with vascular invasion, were observed in a surveillance program. RESULTS: The relapse rate after orchiectomy alone was 30.6% at 5 years. Presence of vascular invasion together with embryonal carcinoma and rete testis invasion in the testicular primary identified a group with a relapse risk of 50%. Without risk factors, the relapse risk was 12%. Eighty percent of relapses were diagnosed within the first year after orchiectomy. The median time to relapse was 5 months (range, 1 to 308 months). Early relapses were mainly detected by increase in tumor markers, and late relapses were detected by computed tomography scans. Relapses after 5 years were seen in 0.5% of the whole cohort or in 1.6% of relapsing patients. The majority of relapses (94.4%) belonged to the good prognostic group according to the International Germ Cell Cancer Collaborative Group classification. The disease-specific survival at 15 years was 99.1%. CONCLUSION: A surveillance policy for patients with stage I NSGCC is a safe approach associated with an excellent cure rate and an overall low treatment burden despite a high relapse rate in a small group of patients. We recommend surveillance for patients with stage I NSGCC with immediate systemic treatment at relapse. Clearly defined risk factors for relapse are presented if an option of risk-adapted treatment is preferred.

A nationwide cohort study of stage I seminoma patients followed on a surveillance program.

BACKGROUND: Increasing concerns about late effects after adjuvant treatment for stage I seminoma have made surveillance an attractive alternative. OBJECTIVE: To evaluate the surveillance strategy in a nationwide cohort study. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, population-based study of Danish patients diagnosed with stage I seminoma between 1984 and 2008 and followed for 5 yr (n=1954). Patient data were linked with national registries on November 30, 2012, to obtain information on late relapse, vital status, and cause of death. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disease-specific survival (DSS), overall survival, relapse rates, time to relapse, detection of relapse, and prognostic factors for relapse were described for the cohort. The Kaplan-Meier method was used to determine survival probabilities. A Cox proportional hazards model was used for multivariate analysis of prognostic factors. RESULTS AND LIMITATIONS: Median follow-up time was 15.1 yr. In total, 369 patients relapsed after a median 13.7 mo. DSS after 15 yr was 99.3%. Tumor size was a significant factor for relapse. Either vascular invasion or invasion of epididymis was significant if the other factor was excluded from analysis. Limitations include the retrospective nature of the study and the number of missing values in analysis. CONCLUSIONS: In the world's largest study of stage I seminoma patients, we found surveillance to be a safe alternative to adjuvant therapies. Tumor size was a significant factor for relapse, together with either invasion of epididymis or vascular invasion. PATIENT SUMMARY: In this nationwide study, we looked at the outcomes of patients with stage I seminoma followed for 5 yr. We found that surveillance is a safe alternative to adjuvant treatment.

The Danish Twin Registry.

INTRODUCTION: The Danish Twin Registry is a unique source for studies of genetic, familial and environmental factors on life events, health conditions and diseases. CONTENT: More than 85,000 twin pairs born 1870-2008 in Denmark. VALIDITY AND COVERAGE: Four main ascertainment methods have been employed. Completeness of ascertainment varies according to birth cohorts. For birth cohorts 1870-1930 both twins should survive to age 6 years. From 1931-1968 72% of all twin pairs has been ascertained, with complete ascertainment of all live born twins since 1968. CONCLUSION: Because twins have been identified independent of traits and on a population basis, the Danish Twin Registry is well suited for studies to understand the influence of genetic and environmental factors for a wide variety of diseases and traits.