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At 23 years of follow-up in the SPCG-4 trial, mortality among men who underwent radical prostatectomy was 11.7 percentage points lower than that among men whose condition was managed by watchful waiting. Radical prostatectomy was associated with a mean of nearly 3 years of extra life.

The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up. 1 By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer–specific or overall mortality after 12 years. 2 PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time . . .

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: Although the prognosis of localised prostate cancer is good, the negative effects of prostate cancer treatment often impair patient quality of life. A growing number of men experience these negative effects over a longer time because of the increased incidence of and prolonged survival in prostate cancer, and the ageing of the population. Only a few studies have investigated the adverse effects of different prostate cancer treatments using large population-based samples. Methods: We conducted a nationwide survey ( n =1239) to collect detailed information regarding the negative effects (i.e., the occurrence, perceived level and perceived bother since the beginning of the treatment) of prostate cancer treatments: radical prostatectomy, external beam radiotherapy, brachytherapy, hormone therapy and surveillance. Furthermore, we measured patient satisfaction with the outcome of the treatment and their psychological well-being (i.e., psychological symptoms and satisfaction with life) 5 years after diagnosis. The negative effects between the treatments were compared, and the determinants of satisfaction and psychological well-being were investigated. Results: The negative effects of all types of active prostate cancer treatments were common and persistent (33–48% reported symptoms at 5 years) and showed the known differences between the treatments. Prostatectomy and the radiotherapies caused urinary leakage; radiotherapy also caused symptoms of urinary irritation; and external radiation also caused bowel dysfunction. Most symptoms were considered highly bothersome. Most respondents (81−93%) reported that their treatment negatively affected their sex lives; 70–92% reported sexual dysfunction; and 20–58% reported that their sex lives with their spouses had ended. Urinary symptoms were especially associated with poorer psychological outcomes. The perception of symptom level and bother had a greater effect on patient satisfaction and well-being than the symptoms per se. Conclusion: Multiple and persistent negative effects follow active prostate cancer treatment, and these effects predict long-term patient satisfaction and psychological well-being. The harms and benefits associated with prostate cancer treatments should be considered when selecting whether and how to actively treat prostate cancer.

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.

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.

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.

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.

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.