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The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 [1·58–1·69] including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Each centre had its own funding responsibility.

PurposeOur purpose was to explore the prognosis of aggressive breast cancers of the HER2 oncogene amplification (HER2 +) and triple-negative (TN) subtypes detected by screening, as well as the prognosis of interval cancers (clinically due to symptoms between screening rounds) and cancers in screening nonparticipants.MethodsThe study population comprised of 823 breast cancers in women aged 50–69 years from 2006–2014. Of these, 572 were found by screening mammography (69%), 170 were diagnosed between the screening rounds (21%), and 81 were diagnosed in women who did not participate in the screening program (10%).ResultsThe majority of all HER2 + (59%) and TN cancers (57%) in this age group were detected by screening. Screen-detected HER2 + tumors were small (median 12 mm), and node-negative (84%). During a median follow-up of eight years, the distant disease-free survival of screen-detected HER2 + and TN cancers was better than that of interval and nonparticipant cancers (age-adjusted HR = 0.16, 95% CI 0.03–0.81 and HR = 0.09, 95% CI 0.01–0.79, respectively). In nonparticipants, the distant disease-free survival of these cancers was worse than in participants (age-adjusted HR = 2.52, 95% CI 0.63–10.11 and HR = 5.30, 95% 1.16–24.29, respectively).ConclusionIn the 50–69 age group, the majority of HER2 + and TN cancers can be found by a quality assured population-based mammography screening. Despite their generally aggressive behavior, after a median follow-up of 8 years, distant disease-free survival was over 90% of these cancers detected by screening. The worst prognosis of these cancers was in women who did not participate in screening.

The European Randomized Study of Screening for Prostate Cancer continues to show a 21% reduction in prostate-cancer mortality in the screening group, after 11 years of follow-up. The number of cancers that would need to be detected to prevent one prostate-cancer death is 37. Screening does not affect all-cause mortality. Screening for prostate cancer has remained controversial, despite results showing a significant reduction in the rate of death from prostate cancer (relative reduction, 20%) among men offered screening for prostate-specific antigen (PSA). 1 The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a multicenter trial initiated in 1991 in the Netherlands and in Belgium, with five more European countries (Sweden, Finland, Italy, Spain, and Switzerland) joining between 1994 and 1998. Recruitment was completed in these centers between 1995 and 2003. Later, France also joined, with enrollment in 2000–2005, but data from the French cohort were not included in the . . .

Background Nowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies. Methods A systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999–2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study. Results Currently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time. Conclusions Our findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.

To evaluate the performance of Charlson Comorbidity Index (CCI) calculated using hospitalization and medication reimbursement databases in predicting mortality. Information on hospitalizations was obtained from the national Care Register for Health Care (HILMO) and on medication reimbursements and entitlements for special reimbursements for medications from the Social Insurance Institution for 77,440 men aged 56-71 years at baseline. The subjects were followed up for mortality via Statistics Finland with 20,562 deaths during a 13-year follow-up. Compared to a CCI score of 0, the age-adjusted hazard ratio for all-cause mortality associated with HILMO-based CCI scores of 1, 2 and 3 or more were 2.39 (95% CI 2.29-2.49), 2.96 (95% CI 2.81-3.13) and 6.42 (95% CI 5.95-6.93) at 13 years. The C-statistic was 0.72 at 1, 0.68 at 5 and 0.66 at 13 years, with only minor improvement over age alone (0.10, 0.06 and 0.04 accordingly). Addition of medication data did not improve predictive abilities and medication-based CCI performed poorly on its own. The hospitalization-based CCI, as well as that based on both databases, predicts relative mortality adequately, but its discriminative ability diminishes over time. Conditions related to hospitalizations affect survival more than medications.

These risks should now be considered in radiation protection measures and policies

Purpose Screening for prostate cancer may have limited impact on decreasing prostate cancer-related mortality. A major disadvantage is overdiagnosis, whereby lesions are identified that would not have become evident during the man’s lifetime if screening had not taken place. The present study aims to estimate the rate of overdiagnosis using Finnish data from the European randomized trial of prostate cancer screening. Methods We used data from 80,149 men randomized to a screening or a control group, distinguishing four birth cohorts. We used the “catch-up method” to identify when the difference in the cumulative incidence of prostate cancer between the screening and control groups had stabilized, implying that the screening has no further effect. We define the overdiagnosis rate to be the relative excess cumulative incidence in the screened group at that point. As an independent method, we also examined the diagnosis rates of T1c tumors as an indicator of early tumors detected by PSA. Results The estimates of overdiagnosis rates from the catch-up method using the full period of available follow-up ranged between cohorts from 2.3% to 15.4%, and the T1c analysis gave very similar results. Conclusion Some overdiagnosis has occurred, but there is uncertainty about its extent. A long follow-up is required to demonstrate the full impact of screening. We evaluated the overdiagnosis rates at a population level, associated with being offered screening, taking account of contamination (screening among the controls). The overall evaluation of screening should incorporate mortality benefit, cost-effectiveness, and quality of life.

The coagulation cascade is thought to contribute to cancer progression. Although in vitro studies suggest that anticoagulants, such as warfarin, might reduce cancer progression, epidemiological data indicate that warfarin users may have a higher risk of cancer mortality. However, single nucleotide polymorphisms (SNPs) that influence warfarin dosing might affect this association. We investigated the risk associations between warfarin use and prostate cancer (PCa) survival, considering the SNP genotypes of CYP2C9 and VKORC1 , which are known to impact both warfarin pharmacokinetics and pharmacodynamics, resulting in lower warfarin dose requirement. We genotyped 2,246 Finnish men with PCa from two different cohorts for SNPs rs1057910, rs1799853, and rs9923231. Genotyping was done using a custom Illumina iSelect genotyping array (iCOGs). Using Cox regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for the risk of overall death, cancer deaths overall, and PCa-specific death after PCa diagnosis based on SNP genotypes. Data on warfarin purchases was obtained from a national registry. Our findings revealed that the SNPs did not alter the risk of cancer or PCa death in either cohort, nor did they modify the risk among warfarin users. However, overall mortality was higher among warfarin users compared to non-users, particularly in carriers of all three SNPs. Even though the increased mortality is likely due to confounding by indication, warfarin use may increase overall mortality especially in men with lower warfarin dose requirements due to SNP carrier status. However, we need further studies with larger populations to confirm these findings.

Quality-of-Life Effects of PSA Screening PSA screening of men between the ages of 55 and 69 years resulted in a reduction in deaths from prostate cancer. However, when overdiagnosis and treatment sequelae were considered, the number of quality-adjusted life-years gained through screening was also reduced. After a median follow-up of 9 years, the initial results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) showed a significant relative reduction of 20% in prostate-cancer mortality among men undergoing prostate-specific antigen (PSA) screening, with a reduction of 27% after adjustment for selection bias. 1 In recently updated results at 11 years, the relative reduction in prostate-cancer mortality in the screening group was 29% after adjustment for selection bias. 2 At the Gothenburg center in the ERSPC, there was a reduction of 44% in prostate-cancer mortality after a median follow-up of 14 years among all men (including those . . .

Objectives Inhaled radon gas is a known alpha-emitting carcinogen linked especially to lung cancer. Studies on higher concentrations of indoor radon and childhood leukemia have conflicting but largely negative results. In this study, we aimed to create a sophisticated statistical model to predict indoor radon concentrations and apply it to a Finnish childhood leukemia case-control dataset. Methods Prediction was based on ~80 000 indoor radon measurements, which were linked to national registries for potential indoor radon predictors based on the literature. In modelling, we used classical methods, random forests and deep neural networks. We had 1093 cases and 3279 controls from a nationwide case-control study. We estimated odds ratio (OR) for childhood leukemia using conditional logistic regression adjusted for potential confounders. Results The r of the final log-linear model was 0.21 for houses and 0.20 for apartments. Using random forest method, we were able to obtain slightly better fit for both houses (r = 0.28) and apartments (r = 0.23). In a risk analysis based on the case-control data with log-linear model, we observed a non-significant (P=0.54) increase with predicted radon concentrations [OR for the 2 quartile 1.08, 95% confidence interval (CI) 0.77-1.50, OR 1.10 with 95% CI 0.79-1.53 for the 3 , and 1.29 with 95% CI 0.93-1.77 for the highest quartile]. Conclusions Our modelling and the previously published models performed similarly but involves major uncertainties, and the results should be interpreted with caution. We observed a slight non-significant increase in risk of childhood leukemia related to higher average indoor radon concentrations.