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Hereditary factors have a strong influence on prostate cancer (PC) risk and poorer outcomes, thus stratification by genetic factors addresses a critical need for targeted PC screening and risk-adapted follow-up. In this Finnish population-based retrospective study 2283 clinically diagnosed and 455 screen-detected patients from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), 2400 healthy individuals have been involved. Individual genetic risk through establishment of a polygenic risk score based on 55 PC risk SNPs identified through the Finnish subset of the Collaborative Oncological Gene-Environment Study was assessed. Men with PC had significantly higher median polygenic risk score compared to the controls (6.59 vs. 3.83, P  < 0.0001). The polygenic risk score above the control median was a significant predictor of PC (OR 2.13, 95% CI 1.90–2.39). The polygenic risk score predicted the risk of PC with an AUC of 0.618 (95% CI 0.60–0.63). Men in the highest polygenic risk score quartile were 2.8—fold (95% CI 2.4–3.30) more likely to develop PC compared with men in the lowest quartile. In the FinRSPC cohort, a significantly higher percentage of men had a PSA level of ≥ 4 ng/mL in polygenic risk score quartile four compared to quartile one (18.7% vs 8.3%, P  < 0.00001). Adding the PRS to a PSA-only model contributed additional information in predicting PC in the FinRSPC model. Results strongly suggest that use of the polygenic risk score would facilitate the identification of men at increased risk for PC.

The European Randomized Study of Screening for Prostate Cancer (ERSPC) was initiated in 1993 to assess the effect of prostate-specific antigen (PSA) testing on prostate cancer mortality. Because deaths from prostate cancer are expected to rise worldwide owing to increased life expectancy and population growth, a final analysis of the long-term outcomes of prostate cancer screening is essential to understanding the benefits and harms of PSA testing. We updated the findings from ERSPC, a multicenter, randomized study conducted across eight European countries with a focus on a predefined core age group of 162,236 men who were 55 to 69 years of age at the time of randomization. Participants were randomly assigned to the screening group and offered repeated PSA testing or to the control group and not invited for screening. The primary outcome was prostate cancer mortality. After a median follow-up of 23 years, prostate cancer mortality was 13% lower in the screening group (rate ratio, 0.87; 95% confidence interval [CI], 0.80 to 0.95), and the absolute risk reduction was 0.22% (95% CI, 0.10 to 0.34). The cumulative incidence of prostate cancer was higher in the screening group than in the control group (rate ratio, 1.30; 95% CI, 1.26 to 1.33). At a median of 23 years of follow-up, one death from prostate cancer was prevented for every 456 men (95% CI, 306 to 943) who were invited for screening, and one death from prostate cancer was averted for every 12 men (95% CI, 8 to 26) in whom prostate cancer was diagnosed, as compared with one death from prostate cancer prevented for every 628 men (95% CI, 419 to 1481) and one death averted for every 18 men (95% CI, 12 to 45) at 16 years of follow-up. Long-term follow-up confirms a sustained reduction in deaths from prostate cancer with PSA testing, alongside an improved harm-benefit ratio. Future screening strategies should adopt risk-based approaches to minimize overdiagnosis while maintaining clinical benefits. (Funded by the Dutch Cancer Society and others; ERSPC ISRCTN registry number, ISRCTN49127736.).

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.

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.

The aim of this study was to investigate pre- and post-diagnostic use of antihypertensive drugs on prostate cancer (PCa)-specific survival and the initiation of androgen deprivation therapy (ADT). The cohort investigated 8,253 PCa patients with 837 PCa-specific deaths during the median follow-up of 7.6 years after diagnosis. Information on drug use, cancer incidence, clinical features of PCa, and causes of death was collected from Finnish registries. Hazard ratios with 95% confidence intervals were calculated using Cox regression with antihypertensive drug use as a time-dependent variable. Separate analyses were performed on PCa survival related to pre- and post-diagnostic use of drugs and on the initiation of ADT. Antihypertensive drug use overall was associated with an increased risk of PCa-specific death (Pre-PCa: 1.21 (1.04-1.4), Post-PCa: 1.2 (1.02-1.41)). With respect to the separate drug groups, angiotensin II type 1 receptor (ATr) blockers, were associated with improved survival (Post-PCa: 0.81 (0.67-0.99)) and diuretics with an increased risk (Post-PCa: 1.25 (1.05-1.49)). The risk of ADT initiation was slightly higher among antihypertensive drug users as compared to non-users. In conclusion, this study supports anti-cancer effect of ATr blockers on PCa prognosis and this should be investigated further in controlled clinical trials.

Background Over the decades, global public health efforts have sought to reduce socio-economic health differences, including differences in mental health. Only a few studies have examined changes in socio-economic differences in psychological symptoms over time. The aim of this study was to assess trends in socio-economic differences in self-reported insomnia and stress over a 24-year time period in Finland. Methods The data source is a repeated cross-sectional survey “Health Behaviour and Health among the Finnish Adult Population” (AVTK), from the years 1979 to 2002, divided into five study periods. Indicators for socio-economic status included employment status from the survey, and educational level and household income from the Statistics Finland register data. We studied the age group of 25–64 years (N = 70115; average annual response rate 75%). Outcome measures were single questions of self-reported insomnia and stress. Results The overall prevalence of insomnia was 18-19% and that of stress 16-19%. Compared to the first study period, 1979–1982, the prevalence of stress increased until study period 1993–1997. The prevalence of insomnia increased during the last study period, 1998–2002. Respondents who were unemployed or had retired early reported more insomnia and stress over time among both men and women. Lower education was associated with more insomnia especially among men; and conversely, with less stress among both sexes. Compared to the highest household income level, those in the intermediate levels of income had less stress whereas those in the lowest income levels had more stress among both sexes. Income level differences in insomnia were less consistent. In general, socio-economic differences in self-reported insomnia and stress fluctuated some, but did not change substantially over the study period 1979–2002. Conclusions Self-reported insomnia and stress were more common during later study periods. The socio-economic differences in insomnia and stress have remained fairly stable over a 24-year time period. However, some of the associations in socio-economic differences were curvilinear and converse. Future studies are needed to explore the complex socio-economic gradients, especially in stress.

In contrast to earlier studies which have used modelling to perform cost-effectiveness analysis, this study links data from a randomised controlled trial with register data from nationwide registries to reveal new evidence on costs, effectiveness, and cost-effectiveness of organised mass prostate-cancer screening based on prostate-specific antigen (PSA) testing. Cost-effectiveness analyses were conducted with individual-level data on health-care costs from comprehensive registers and register data on real-world effectiveness from the two arms of the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), following 80,149 men from 1996 through 2015. The study examines cost-effectiveness in terms of overall mortality and, in addition, in terms of diagnosed men's mortality from prostate cancer and mortality with but not from prostate cancer. Neither arm of the FinRSPC was clearly more cost-effective in analysis in terms of overall mortality. Organised screening in the FinRSPC could be considered cost-effective in terms of deaths from prostate cancer: averting just over one death per 1000 men screened. However, even with an estimated incremental cost-effectiveness ratio of below 20,000€ per death avoided, this result should not be considered in isolation. This is because mass screening in this trial also resulted in increases in death with, but not from, prostate cancer: with over five additional deaths per 1000 men screened. Analysis of real-world data from the FinRSPC reveals new evidence of the comparative effectiveness of PSA-based screening after 20 years of follow-up, suggesting the possibility of higher mortality, as well as higher healthcare costs, for screening-arm men who have been diagnosed with prostate cancer but who do not die from it. These findings should be corroborated or contradicted by similar analyses using data from other trials, in order to reveal if more diagnosed men have also died in the screening arms of other trials of mass screening for prostate cancer.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.

IntroductionDiabetes mellitus has been linked with adverse prostate cancer (PCa) outcomes. However, role of hyperglycemia in PCa progression is unclear. We evaluated the link between hyperglycemia and PCa survival among Finnish PCa patients.MethodsThe study cohort included 1770 men with data on fasting glucose and diagnosed with PCa within the Finnish Randomized Study of Screening for PCa in 1995–2009. Additionally, 1398 men had data on glycated hemoglobin (HbA1c). Information on fasting glucose and HbA1c measurements was obtained from the regional laboratory database. Antidiabetic medication use was obtained from the prescription database of the Social Insurance Institution (SII). Time-dependent Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals for PCa death among diabetic, impaired glucose tolerant, and normoglycemic men.ResultsDuring median follow-up of 9.9 years after the diagnosis, 182 men died from PCa. After adjustment for tumor stage, Gleason grade, and PSA level at diagnosis, diabetic fasting glucose level after PCa diagnosis was associated with elevated risk of PCa death compared to normoglycemic men (HR 1.67 95% CI 1.18–2.36). The risk association was strongest among participants with localized cancer at diagnosis; HR 2.39, 95% CI 1.45–3.93. The risk elevation was observed for glucose measurements taken up to 5 years earlier. Diabetic glucose levels measured before the diagnosis were not associated with PCa death.ConclusionOur study cohort suggests an increased risk of PCa death in men with diabetic fasting blood glucose levels, supporting the role of hyperglycemia as a risk factor for PCa progression.