Statin Use and Prostate Cancer Survival in the Finnish Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Recent research has suggested that statins have an effect on prostate cancer prognosis. It is currently unclear how prostate cancer screening, tumor and patient characteristics, or treatment selection may affect this association. OBJECTIVE: To evaluate the risk of prostate cancer death among statin users. To determine how disease and treatment characteristics affect the association. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study consisting of a general male population of Finland participating in the Finnish Randomized Study for Prostate Cancer Screening. The cohort of consisted of 6537 prostate cancer cases diagnosed in the Finnish Randomized Study of Screening for Prostate Cancer population during 1996-2012. The cohort was linked to the National Prescription Database for information on the use of statins and other drugs. INTERVENTION: Statin use before and after prostate cancer diagnosis compared with nonuse. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for the risk of prostate cancer death by amount, duration, and intensity of statin use. Cox proportional hazards regression with postdiagnostic statin use as a time-dependent variable. RESULTS: During the median follow-up of 7.5 yr postdiagnosis 617 men died of prostate cancer. Statin use after diagnosis was associated with a decreased risk of prostate cancer death (HR 0.80; 95% confidence interval 0.65-0.98). A decreasing risk trend was observed by increasing intensity of usage (doses/year). The risk decrease was clearest in men managed with androgen deprivation therapy. Prediagnostic statin use was not associated with risk of prostate cancer death (HR 0.92; 95% confidence interval 0.75-1.12). CONCLUSIONS: Decreased risk of prostate cancer death by statin use after diagnosis suggests that statins may delay or prevent prostate cancer progression. The risk decrease was significant only in men managed with androgen deprivation therapy, but statistical power was limited to estimate the association in men managed with surgery or radiotherapy. PATIENT SUMMARY: Use of statins after prostate cancer diagnosis was associated with a decreased risk of prostate cancer death. The risk decrease was dose-dependent and observed especially among patients treated with hormone therapy.

Postscreening follow-up of the Finnish Prostate Cancer Screening Trial on putative prostate cancer risk factors: vitamin and mineral use, male pattern baldness, pubertal development and non-steroidal anti-inflammatory drug use.

Objective The etiology of prostate cancer (PCa) is still unclear. This study aimed to investigate the association between PCa risk and the indicators of endogenous androgen production at puberty, male pattern baldness, over-the-counter use of non-steroidal anti-inflammatory drugs and vitamin supplement use. Materials and methods Participants in the third round of the Finnish Prostate Cancer Screening Trial were sent a survey on possible PCa risk factors and 11,795 out of 12,740 (93%) men returned the questionnaire. PCa cases were identified from the Finnish Cancer Registry. Results During the median follow-up of 6.6 years, 757 PCa cases were diagnosed and 21 men died from PCa. Compared to earlier onset, puberty onset after 15 years of age was associated with a borderline significant decrease in PCa risk [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.75-1.00] but not with PCa mortality. Weekly use of ibuprofen was associated with an increased risk of PCa overall (HR 1.43, 95% CI 1.08-1.91) and with metastatic PCa (HR 1.49, 95% CI 1.12-1.99) compared to less frequent use. No statistically significant association was found between vitamin use and PCa. Conclusions This study suggests that the timing of initiation of endogenous androgen production at puberty may have importance for later PCa development. Current use of over-the-counter ibuprofen is associated with an increased risk of PCa. There was no evidence of any protective effects of vitamin use on PCa risk.

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC.

BACKGROUND: We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis. METHODS: We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers. RESULTS: Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45-0.65) and MST 6.3 (95% CI 4.2-8.3) years. The overall overdiagnosis was 42% (95% CI 37-52) of the screen-detected cancers, with 58% (95% CI 54-65) in men with the lower and 37% (95% CI 31-47) in those with higher polygenic risk. CONCLUSION: Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed.

Use of non-steroidal anti-inflammatory drugs and prostate cancer survival in the Finnish prostate cancer screening trial.

BACKGROUND: Growing evidence suggests that aspirin is associated with decreased prostate cancer (PCa) mortality. The effect of other NSAID use on risk of PCa death remains controversial. We examined prostate cancer survival among aspirin and other NSAID users in the Finnish Prostate Cancer Screening Trial. METHODS: A total of 6,537 men were diagnosed with prostate cancer in 1996-2009 among the 80,144 men in the trial and 617 died from prostate cancer during the median follow-up of 7.5 years after the diagnosis. Prescription drug purchases information was obtained from the national reimbursement database. We calculated hazard ratios and 95% confidence intervals for PCa-specific survival using multivariable-adjusted Cox regression analysis separately for NSAID and aspirin usage before and after the diagnosis. RESULTS: We observed an increased risk of PCa death associated with both pre- and post-diagnostic NSAID usage (HR 1.30, 95%CI 1.07-1.58 and HR 2.09, 95%CI 1.75-2.50, respectively). An increasing risk trend was observed by cumulative dose and intensity of NSAID use. When the last three years were excluded from the analysis, the death risk diminished to a protective level (HR 0.42, 95%CI 0.34-0.51 and HR 0.30 95%CI 0.24-0.39). Aspirin use was not significantly associated with prostate cancer survival. CONCLUSIONS: The survival decrease among NSAID users is likely explained by symptomatic treatment of metastatic pain in patients with advanced PCa. However, results of the lag time analysis support previous findings of a possible preventative action of NSAIDs.

Family history in the Finnish Prostate Cancer Screening Trial.

Family history (FH) is one of the few known risk factors for prostate cancer (PC). There is also new evidence about mortality reduction in screening of PC with prostate-specific antigen (PSA). Therefore, we conducted a prospective study in the Finnish Prostate Cancer Screening Trial to evaluate the impact of FH on outcomes of PC screening. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm and were invited for screening with PSA test (cut-off 4 ng/ml) every 4 years. At the time of each invitation, FH of PC (FH) was assessed through a questionnaire. The analysis covered a follow-up of 12 years from randomization for all men with data on FH. Of the 23,702 (74.3%) invited men attending screening, 22,756 (96.0%) provided information of their FH. Altogether 1,723 (7.3%) men reported at least one first-degree relative diagnosed with PC and of them 235 (13.6%) were diagnosed with PC. Men with a first-degree FH had increased risk for PC (risk ratio (RR) 1.31, p < 0.001) and the risk was especially elevated for interval cancer (RR 1.65, 95% CI 1.27-2.15). Risk for low-grade (Gleason 2-6) tumors was increased (RR 1.46, 95% CI 1.15-1.69), but it was decreased for Gleason 8-10 tumors (RR 0.48, 95% CI 0.25-0.95). PSA test performance (sensitivity and specificity) was slightly inferior for FH positives. No difference in PC mortality was observed in terms of FH. Our findings provide no support for selective PSA screening targeting men with FH of PC.

The Finnish prostate cancer screening trial: analyses on the screening failures.

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non-participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four-year intervals and referred to biopsy if the PSA concentration was ≥ 4.0 ng/ml, or 3.0-3.99 ng/ml with a free/total PSA ratio ≤ 16%. The median follow-up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non-participants, the screen-negative men with PSA ≥ 3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76-1.04). After correcting for non-attendance, the HR was 0.78 (0.64-0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74-1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74-1.04). Non-participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.

Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Each centre had its own funding responsibility.

Health-related quality of life in the Finnish trial of screening for prostate cancer.

BACKGROUND: Evidence of the potential impact of systematic screening for prostate cancer (PCa) on health-related quality of life (HRQoL) at a population-based level is currently scarce. OBJECTIVE: This study aims to quantify the long-term HRQoL impact associated with screening for PCa. DESIGN, SETTING, AND PARTICIPANTS: Postal questionnaire surveys were conducted in 1998, 2000, 2004, and 2011 among men in the Finnish PCa screening trial diagnosed with PCa (total n=7011) and among a random subsample of the trial population (n=2200). In 2011, for example, 1587 responses were received from men with PCa in the screening arm and 1706 from men in the control arm. In addition, from the trial subsample, 549 men in the screening arm and 539 in the control arm provided responses. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health-state-value scores were compared between the intervention and control arms using three distinct HRQoL measures (15D, EQ-5D, and SF-6D), and statistical significance was assessed using t tests. In addition, differences over repeated assessments of HRQoL between groups were evaluated using generalised estimating equations. RESULTS AND LIMITATIONS: In the 2011 survey, a small but statistically significant difference emerged between the trial arms among men diagnosed with PCa (mean scores, screening vs control arm: 15D: 0.872 vs 0.866, p=0.14; EQ-5D: 0.852 vs 0.831, p=0.03; and SF-6D: 0.763 vs 0.756, p=0.06). Such differences in favour of the screening arm were not found among the sample of men from the trial (15D: 0.889 vs 0.892, p=0.62; EQ-5D: 0.831 vs 0.852, p=0.08; and SF-6D: 0.775 vs 0.777, p=0.88). The slight advantage with screening among men with PCa was reasonably consistent across time in the longitudinal analysis and was strongest among men with early-stage disease. CONCLUSIONS: These results show some long-term HRQoL benefit from screening for men with PCa but suggest little impact overall in the trial population.

Effects of prostate cancer screening on health-related quality of life: results of the Finnish arm of the European randomized screening trial (ERSPC).

BACKGROUND: As prostate cancer (PC) mortality reduction results are not unequivocal, a special emphasis has to be put on other aspects of the prostate-specific antigen (PSA) screening, including effects on quality of life. In the present study we describe the short-term effects of various phases of PC screening on health-related quality of life (HRQL). MATERIAL AND METHODS: The study participants were randomized into the screening arm within the Finnish component of the European Randomized Study on Screening for Prostate Cancer (ERSPC). The RAND 36-Item Health Survey on HRQL and questionnaires on sociodemographic and behavioral factors were delivered to participants at various phases of the first screening round: 1) 500 participants at invitation; 2) 500 after screening; 3) 500 after obtaining the PSA result; 4) to 300 participants after undergoing digital rectal examination (DRE) (but prior to being informed of its result); and 5) approximately 300 after prostate biopsy. At each stage, a new sample of participants was recruited. RESULTS: Response rates were 59% at invitation, 77% after PSA blood test, 54% after PSA result and 69% after DRE. The men recruited at each stage were comparable in respect to socioeconomic variables. The HRQL scores in RAND-36 subscales showed little variation in the different phases of the screening process. Compared with the previous phase, the social function score was slightly lower after obtaining the PSA result than after blood test, the emotional role score lower after DRE than after PSA result and the pain-related score lower after DRE than after TRUS and biopsy. The screening participants were comparable to the general population as their HRQL scores were similar to an age-stratified general Finnish male population. CONCLUSION: Short-term HRQL effects of prostate cancer screening appear minor and transient.

Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate-specific antigen (PSA) concentration in the Finnish prostate cancer screening trial.

OBJECTIVE: To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy. MATERIALS AND METHODS: Study subjects were men aged 54-67 years with an elevated PSA (≥4 ng/mL or 3-4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996. A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation. Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry. The median length of follow-up was 10.5 years. Cox regression analysis was used to assess PCa risk after the initial benign biopsy. RESULTS: Histological inflammation was found in 66% of the biopsies. Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35-1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46-1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42-1.07; P = 0.092). CONCLUSIONS: Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance. Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Prostate cancer mortality in the Finnish randomized screening trial.

BACKGROUND: Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. METHODS: A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided. RESULTS: PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms. CONCLUSIONS: At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.

Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC).

BACKGROUND: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. OBJECTIVE: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. DESIGN, SETTING, AND PARTICIPANTS: Data were available for 76,813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. INTERVENTION: Regular screening based on serum PSA measurements was offered to 36270 men randomized to the screening arm, while no screening was provided to the 40543 men in the control arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. RESULTS AND LIMITATIONS: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p<0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p=0.001) in the intention-to-screen analysis and a 42% (p=0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. CONCLUSIONS: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736.

Prostate-cancer mortality at 11 years of follow-up.

BACKGROUND: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. METHODS: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. RESULTS: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality. CONCLUSIONS: Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Number of screens for overdetection as an indicator of absolute risk of overdiagnosis in prostate cancer screening.

As with wide-spread use of prostate cancer (Pca) screening with prostate-specific antigen testing, overdetection has increasingly gained attention. The authors aimed to estimate absolute risk of overdetection (RO) in Pca screening with various interscreening intervals and ages at start of screening. We estimated age-specific preclinical incidence rates (per 100,000 person-years) for progressive cancer (from 128 for age group 55-58 years to 774 for age group 67-71 years) and nonprogressive cancer (from 40 for age group 55-58 years to 66 for age group 67-71 years), the mean sojourn time (7.72 years) and the sensitivity (42.8% at first screen and 59.8% at the second screen) by using a multistep epidemiological model with data from the Finnish randomized controlled trial. The overall number of screens for overdetection (NSO) was 29 (95% confidence interval (CI): 18, 48) for screenees aged 55-67 years, equivalent to 3.4 (95% CI: 2.1, 5.7) overdetected Pcas per 100 screenees. The NSO decreased from 63 (95% CI: 37, 109) at the first screen to 29 (95% CI: 18, 48) at the third screen and from 43 (95% CI: 36, 52) for age 55 years to 25 (95% CI: 8, 75) at age 67 years at the first screen. In conclusion, around 3.4 cases for every 100 screened men would be overdetected during three screen rounds (~ 13 years of follow-up) in the Finnish randomized controlled trial. Elucidating the absolute RO under various scenarios makes contribution for evaluating the benefit and harm of Pca screening.

False-positive screening results in the European randomized study of screening for prostate cancer.

BACKGROUND: Screening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial. MATERIALS AND METHODS: We included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2-7 year interval depending on the centre; PSA cut-off was 3.0-4.0 ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1 year was defined as an FP result. RESULTS: Of the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6-2.7% of men with negative screen, risk ratio 3.8-3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result. CONCLUSIONS: Our results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels.

Prostate cancer screening: a survey of attitudes and practices among Finnish physicians in 1999 and 2007.

OBJECTIVE: To evaluate the attitudes and practices related to prostate-specific antigen (PSA) screening for prostate cancer (PC) among Finnish physicians in 1999 and 2007. MATERIALS AND METHODS: The first questionnaire survey was conducted in 1999 with a mailing to 102 urologists, 679 community physicians and 684 occupational health physicians identified from the membership files of three medical associations. The area of residence was divided into the study area of the Finnish PC screening trial and the rest of Finland. The second survey was carried out in 2007 targeting 168 urologists, 1039 community physicians and 938 occupational health physicians. RESULTS: The response proportion was 48% in 1999 and 50% in 2007. In both rounds, urologists regarded PC as a more important public health issue than other physicians. On the other hand, the non-urologists considered early diagnosis and screening more important than the urologists. PC was rated by all physicians as a less important public health problem in 2007 than in 1999. A smaller proportion of urologists found routine PSA testing indicated for asymptomatic men, compared with other physicians (40% versus 74-60% in 1999, P < 0.001 and 35% versus 44-37% in 2007, P = 0.005). The proportion of physicians reporting regular PSA screening in asymptomatic men was reduced from 1999 to 2007 (from 18% to 9%, P < 0.0001). CONCLUSION: Based on reported practices of Finnish urologists, community physicians and occupational health physicians, popularity of PSA testing declined between 1999 and 2007. Urologists found PSA testing among asymptomatic men justified less frequently than the other physicians.

Prediction of prostate cancer in unscreened men: external validation of a risk calculator.

BACKGROUND: Prediction models need external validation to assess their value beyond the setting where the model was derived from. OBJECTIVE: To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). DESIGN, SETTING AND PARTICIPANTS: The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. MEASUREMENTS: The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). RESULTS AND LIMITATIONS: Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both p<0.001). The areas under the curves were 0.76 and 0.78, and substantially lower for the model with PSA only (0.64 and 0.68 respectively). The model proved clinically useful for any decision threshold compared with a model with PSA only, PSA and DRE, or biopsying all men. A limitation is that the model is based on sextant biopsies results. CONCLUSIONS: The ERSPC risk calculator discriminated well between those with and without prostate cancer among initially screened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting.

Results of the three rounds of the Finnish Prostate Cancer Screening Trial--the incidence of advanced cancer is decreased by screening.

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis.

Why do men opt out of prostate-cancer screening? Attitudes and perception among participants and non-participants of a screening trial.

OBJECTIVE: To evaluate attitudes to prostate cancer screening with prostate-specific antigen (PSA) of men who complied with offered screening and those who declined it within the Finnish randomized population-based screening trial, and to compare general health-related quality of life (HRQL) between participants and non-participants. SUBJECTS AND METHODS: Self-administered questionnaires were sent to 500 men randomized into the screening arm in 1996-99 within the Finnish component of the European Randomized Study on Screening for Prostate Cancer. A similar survey was conducted among 500 non-participants. RESULTS: Response proportions among the screening participants and non-participants were 59% and 28%, respectively. Current smoking was less frequent (P < 0.05) among the participants. In terms of attitude, the participants regarded the prostate cancer study as more important and the invitation letter as more informative than the non-participants (P < 0.001). There was no clear difference in worry about treatment consequences. The most commonly given reasons for not participating included previous PSA testing (41%), forgetting the invitation (51%), or not wanting to think of prostate cancer (39%) and regarding possible further diagnostic examinations as unpleasant (28%). The non-participants had a lower mental health score (P < 0.001) than the participants in the RAND-36 Survey. CONCLUSION: Most men who chose not to attend screening had a positive attitude, but did not participate due to practical reasons. However, two-thirds of the non-participants indicated a willingness to participate in the next screening round.

Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial.

Decreased risk of advanced prostate cancer has been reported among men using statins. However, the evidence on overall prostate cancer risk is conflicting. We compared the relative risk between current users and non-users of statins or other cholesterol-lowering medications in a population undergoing systematical prostate cancer screening. The study cohort comprised of 23,320 men participating in the screening arm of the Finnish prostate cancer screening trial during 1996-2004. Information on medication use was obtained from a comprehensive national prescription database. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HRs) for prostate cancer. Serum prostate-specific antigen (PSA) level was compared between current users and non-users of cholesterol-lowering drugs. Compared with medication non-users, the overall prostate cancer incidence was decreased among statin users [HR 0.75, 95% confidence interval (CI) 0.63-0.89]. The inverse association was dose-dependent with cumulative amount of statin use, and strongest for low-grade and early stage tumors. The incidence was nonsignificantly lower also among users of other types of cholesterol-lowering drugs (HR 0.62, 95% CI 0.28-1.38), but without dose-dependence. Age-adjusted median serum PSA tended to be lower among users of cholesterol-lowering drugs, but the relative risk decrease among statin users was not related to decreased PSA. Overall incidence of prostate cancer was lowered among statin users when bias due to differential PSA testing between medication users and non-users was eliminated by systematical prostate cancer screening. Cholesterol-lowering with statins seems beneficial for prostate cancer prevention.