Reduce Prostate Cancer Mortality Research Articles

The role of biomarkers in the assessment of prostate cancer risk prior to prostate biopsy: which markers matter and how should they be used?

Prostate cancer (PCa) screening has been substantially influenced by the clinical implementation of serum prostate-specific antigen (PSA). In this context, improvement of early PCa detection and stage migration as well as reduced PCa mortality were achieved, and up-to-date PSA represents the gold standard biomarker of PCa diagnosis together with clinical findings. Nonetheless, PSA shows weakness in discriminating between malign and benign prostatic disease or indolent and aggressive cancers. As a result, the expansion of PSA screening is extensively debated with regard to overdetection and ultimately overtreatment, keeping in mind that PCa is still the third leading cause of cancer-specific mortality in the Western male population. Consequently, today's task is to increase the accuracy of PCa detection and furthermore to allow stratification for indolent PCa that might permit active surveillance and to filter out aggressive cancers necessitating treatment. Thus, novel biomarkers, especially in combination with approved clinical risk factors (e.g., age or family history of PCa), within multivariable prediction models carry the potential to improve many aspects of PCa diagnosis and to enable risk classification in clinical practice. Multivariable models lead to superior accuracy for PCa prediction instead of the use of a single risk factor. The aim of this article was to present an overview of known risk factors for PCa together with new promising blood- and urine-based biomarkers and their application within risk models that may allow risk stratification for PCa prior to prostate biopsy. Risk models may optimize PCa detection and classification with regard to improved PCa risk assessment and avoidance of unnecessary prostate biopsies.

Radiation Plus Hormone Therapy Reduces Prostate Cancer Mortality

Abstract This updated analysis from the Scandinavian Prostate Cancer Group Study VII trial shows that antiandrogen treatment combined with radiation cut 10- and 15-year prostate cancer–specific mortality rates by more than half compared with antiandrogen treatment alone.

Screening for Prostate Cancer With the Prostate-Specific Antigen Test

Prostate cancer screening with the prostate-specific antigen (PSA) test remains controversial. To review evidence from randomized trials and related modeling studies examining the effect of PSA screening vs no screening on prostate cancer-specific mortality and to suggest an approach balancing potential benefits and harms. MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials were searched from January 1, 2010, to April 3, 2013, for PSA screening trials to update a previous systematic review. Another search was performed in EMBASE and MEDLINE to identify modeling studies extending the results of the 2 large randomized trials identified. The American Heart Association Evidence-Based Scoring System was used to rate level of evidence. Two trials-the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC)-dominate the evidence regarding PSA screening. The former trial demonstrated an increase in cancer incidence in the screening group (relative risk [RR], 1.12; 95% CI, 1.07-1.17) but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09; 95% CI, 0.87-1.36). The ERSPC demonstrated an increase in cancer incidence with screening (RR, 1.63; 95% CI, 1.57-1.69) and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91). The ERSPC documented that 37 additional men needed to receive a diagnosis through screening for every 1 fewer prostate cancer death after 11 years of follow-up among men aged 55 to 69 years (level B evidence for prostate cancer mortality reduction). Harms associated with screening include false-positive results and complications of biopsy and treatment. Modeling studies suggest that this high ratio of additional men receiving diagnoses to prostate cancer deaths prevented will decrease during a longer follow-up (level B evidence). Available evidence favors clinician discussion of the pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only men who express a definite preference for screening should have PSA testing. Other strategies to mitigate the potential harms of screening include considering biennial screening, a higher PSA threshold for biopsy, and conservative therapy for men receiving a new diagnosis of prostate cancer.

Prostate Cancer Mortality in Areas With High and Low Prostate Cancer Incidence

BackgroundThe effect of prostate-specific antigen (PSA) screening on prostate cancer mortality remains debated, despite evidence from randomized trials. We investigated the association between prostate cancer incidence, reflecting uptake of PSA testing, and prostate cancer mortality.MethodsThe study population consisted of all men aged 50 to 74 years residing in eight counties in Sweden with an early increase in prostate cancer incidence and six counties with a late increase during two time periods. Incidence of metastatic prostate cancer was investigated in the period from 2000 to 2009, and prostate cancer–specific mortality and excess mortality were investigated in the period from 1990 to 1999 and the period from 2000 to 2009 by calculating rate ratios for high- vs low-incidence counties and rate ratios for the period from 2000 to 2009 vs the period from 1990 to 1999 within these two groups. All statistical tests were two-sided.ResultsThere were 4528134 person-years at risk, 1577 deaths from prostate cancer, and 1210 excess deaths in men with prostate cancer in high-incidence counties and 2471373 person-years at risk, 985 prostate cancer deaths, and 878 excess deaths in low-incidence counties in the period from 2000 to 2009. Rate ratios in counties with high vs low incidence adjusted for time period were 0.81 (95% confidence interval [CI] = 0.73 to 0.90) for prostate cancer– specific mortality and 0.74 (95% CI = 0.64 to 0.86) for excess mortality, and the rate ratio of metastatic prostate cancer was 0.85 (95% CI = 0.79 to 0.92).ConclusionsThe lower prostate cancer mortality in high-incidence counties reflecting a high PSA uptake suggests that more-intense as compared with less-intense opportunistic PSA screening reduces prostate cancer mortality.

PSA Screening: A Discussion Based on the USPSTF Recommendations and the AUA and EAU Guidelines

The role of prostate-specific antigen (PSA) screening in the adult male population is not clearly defined. Although PSA has been shown to be the single most significant predictive factor for identifying men at increased risk of developing prostate cancer (PCa), PSA screening may lead to an increase in unnecessary prostate biopsies, significant over-diagnoses of PCa, and overtreatment of the disease, each of which may contribute to untoward complications and/or side effects. We reviewed PubMed and MEDLINE for articles published between 1970 to December 2013 that discuss the clinical applications of PSA as a screening test, in addition to clinical trials, evidence-based recommendations and guidelines from major medical organizations both in the U.S. and worldwide regarding prostate cancer screening. We also reviewed the current PSA screening recommendations of the United States Preventive Services Task Force (USPSTF), the American Urological Association (AUA), and the European Association of Urology (EAU). A total of 110 publications were reviewed. Results from the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and Göteborg trials regarding prostate screening are conflicting: The ERSPC and Göteborg trials show a reduction in prostate cancer mortality, but the PLCO trial shows no benefit. The USPSTF has assigned a grade D recommendation to PSA screening, that is, it has recommended against screening for men in the general U.S. population, regardless of age. The AUA updated its guideline in 2013 to reflect its belief that men under the age of 40 or over the age of 70 with less than a 10- to 15-year life expectancy should not be offered or subjected to PSA screening. Men between the ages of 40 and 54 with risk factors (positive family history or African American race), or men of average risk between the ages of 55 and 69 or older if life expectancy is greater than 10 years should be counseled on the risks and benefits of PSA screening and undergo PSA screening if desired. The EAU recommends obtaining a baseline PSA at age 40 to 45 and adapting subsequent screening intervals to that baseline. The diversity of methodology from randomized trials such as the PLCO, ERSPC, and Göteborg, allows for significant flexibility in interpretation, making it difficult to apply trial outcomes to substantiate universal recommendations. Clinical factors, such as age, race, family history, 10-year life expectancy, and patient preferences, should be taken into account. Variations on PSA-based screening, including age-adjusted PSA, PSA density (PSAD), PSA velocity (PSAV), and percentage of free PSA (%fPSA), may be used to improve the performance of the test. PSA testing may serve as the foundation for a more risk-based assessment. Finally, it should be noted that the decision to screen or not to screen using PSA testing is best made by the patient and his urologist after weighing its advantages and disadvantages.

Aktuelle Ergebnisse zur PSA-basierten Früherkennung des Prostatakarzinoms

Prostate cancer is the most common cancer and the third leading cause of cancer-specific death in men in Western industrialized countries. Implementation of the prostate-specific antigen (PSA) blood test as an early detection tool has led to a significant reduction of prostate cancer mortality in the USA. Apart from an earlier detection of clinically relevant tumors, regular PSA testing increases the risk of over-detection and over-treatment of clinically indolent tumors. In our view, a reliable stratification of indolent tumors in active surveillance programs is the key in avoiding or reducing overtreatment of early diagnosed prostate cancers. Along with better risk stratification, the expansion of PSA screening should be discussed in order to reduce the still high numbers of palliative treatments, metastases, and prostate cancer-related deaths.

Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

BackgroundProstate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.MethodsEstimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).ResultsIf PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.ConclusionsProstate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate-Specific Antigen and Prostate Cancer Mortality

Although findings from recently published clinical trials and a review from the U.S. Preventive Services Task Force suggest that there is limited to no prostate cancer mortality benefit associated with prostate-specific antigen (PSA) screening, confusion remains as to whether the use of PSA as a screening tool for prostate cancer is warranted. A systematic literature review was done in 2012 to identify case-control studies from the past 20 years that focused on evaluating the association between screening for prostate cancer and prostate cancer mortality. Emphasis was put on synthesizing the results of these studies, evaluating their limitations, and identifying remaining questions and issues that should be addressed in future studies. A total of seven studies were identified in this time period, with the majority suggesting that a reduction in prostate cancer mortality is associated with PSA screening. However, the findings may be limited by various biases inherent to case-control studies of screening tests, such as selection biases resulting from both case and control subject selection, exposure measurement issues, lead and length biases, and issues specific to prostate cancer screening such as the influence of digital rectal examinations. Findings from existing case-control studies of PSA and prostate cancer mortality suggest that there is a mortality benefit from PSA screening. However, these studies may be limited by bias and must therefore be interpreted with caution. As uncertainty regarding PSA screening remains, future studies to evaluate the association between PSA and prostate cancer mortality should address these potential biases directly.

Prostate-specific Antigen–Based Prostate Cancer Screening: Reduction of Prostate Cancer Mortality After Correction for Nonattendance and Contamination in the Rotterdam Section of the European Randomized Study of Screening for Prostate Cancer

BackgroundLarge randomized screening trials provide an estimation of the effect of screening at a population-based level. The effect of screening for individuals, however, is diluted by nonattendance and contamination in the trial arms. ObjectiveTo determine the prostate cancer (PCa) mortality reduction from screening after adjustment for nonattendance and contamination. Design, setting, and participantsA total of 34 833 men in the core age group, 55–69 yr, were randomized to a screening or control arm in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA) testing was offered to all men in the screening arm at 4-yr intervals. A prostate biopsy was offered to men with an elevated PSA. The primary end point was PCa-specific mortality. Outcome measurements and statistical analysisNonattendance was defined as nonparticipation in the screening arm. Contamination in the control arm was defined as receiving asymptomatic PSA testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs) were calculated with an intention to screen (ITS) analysis and after correction for nonattendance and contamination using a method that preserves the benefits obtained by randomization. Results and limitationsThe ITS analysis resulted in an RR of 0.68 (95% confidence interval [CI], 0.53–0.89) in favor of screening at a median follow-up of 13 yr. Correction for both nonattendance and contamination resulted in an RR of 0.49 (95% CI, 0.27–0.87) in favor of screening. ConclusionsPCa screening as conducted in the Rotterdam section of the ERSPC can reduce the risk of dying from PCa up to 51% for an individual man choosing to be screened repeatedly compared with a man who was not screened. This benefit of screening should be balanced against the harms of overdiagnosis and subsequent overtreatment. Trial registrationISRCTN49127736.

Dietary Fat and Reduced Prostate Cancer Mortality

There are 3 well-established risk factors for prostate cancer: race (specifically, African American race), family history, and age. Unfortunately, we cannot change our race or our parents nor can we stop time. Given this reality, there is much interest in identifying modifiable risk factors for prostate cancer. In a landmark study, Calle and colleagues followed up more than 900 000 persons for more than 16 years and found that obesity was linked with death from 17 different cancer types.1 Although prostate cancer was one of the cancers identified, its association with obesity was modest, with mildly obese (body mass index [calculated as weight in kilograms divided by height in meters squared], 30-34.9) and moderately obese (body mass index, 35-39.9) men being 20% and 34% more likely, respectively, to die of prostate cancer. Even so, given the large number of men who die annually of prostate cancer (258 100 worldwide and 32 600 in North America in 2008)2 and the high prevalence of obesity (35% in the United States in 2012),3 the association means that tens of thousands of men die annually of obesity-related prostate cancer. While the exact links between obesity and prostate cancer are complex, diet and lifestyle invariably play a role.

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.

Prostate cancer overdiagnosis and overtreatment

To summarize the evidence, now extensive, that efforts to reduce prostate cancer mortality by screening and early detection result in overdiagnosis of disease that is clinically insignificant, and would never have been diagnosed in the patient's lifetime in the absence of screening. Overdiagnosis may result in overtreatment, which in the case of prostate cancer often carries significant, long-term quality-of-life effects. The review also addresses the solutions to the problem of overdiagnosis and overtreatment, and summarizes the outcomes of these approaches. Screening for prostate cancer has been demonstrated to reduce mortality, although with a high number needed to treat. One approach to this problem is to offer patients with favorable risk disease an initial conservative approach, with close monitoring and treatment for those patients who are reclassified as higher risk over time. Much preclinical data indicates that Gleason 6 prostate cancer does not carry the hallmarks of malignancy. However, a number of recent studies have demonstrated that in patients diagnosed with favorable risk prostate cancer (Gleason 6 or less, prostate-specific antigen <10), about 30% will harbor higher grade cancer and benefit from treatment. These patients are identifiable by a combination of repeat biopsy, serial prostate-specific antigen, and in borderline cases, multiparametric MRI. Active surveillance is a powerful solution to the problem of overdiagnosis and overtreatment associated with screening for prostate cancer. For the 40-50% of patients with favorable risk prostate cancer, it offers the benefit of personalized medicine, avoiding treatment and related quality-of-life effects altogether in the majority, and providing definitive management for the minority who are reclassified with higher risk disease over time.

U.S. Preventive Services Task Force (USPSTF) recommendations on PSA screening (PSAS) for prostate cancer (PC): Are they justified?

e12535 Background: PSAS has been debated since the Amer Can Soc recommended it in 1992 without data from randomized trials (RTs). Recent RT reports indicate that PSAS does not clearly reduce PC mortality (PCM). In Oct 2011, the USPSTF recommended against PSAS. Does the evidence support this position? Methods: Quebec Trial (QT) randomized 46,193 men 45-80 yrs 2:1 in 1988. Experimental group (EG) was invited for annual PSAS while control group (CG) was not invited. PLCO (Prostate-Lung-Colon-Ovary) randomized 76,693 men 55-74 yrs to annual PSAS or usual care starting in 1993. ERSPC (European study) randomized 162,243 men 55-69 yrs to EG invited to PSAS q4 yrs or CG not invited starting in 1994. Results: QT investigators reported in 1998 that PSAS reduced PCM. The problem was poor compliance with PSAS invitation in QT. Of 30,956 EG, 7,155 (23%) accepted. Of 15,237 CG, 982 (6%) underwent PSAS. Of 8,137 screened (SC), there were 5 PC deaths compared to 137 among 38,056 unSC (RR=0.17; 95% CI: 0.07-0.42). However, this analysis ignores the randomization. Intent to treat (ITT) analysis reveals no PCM reduction (RR=1.11; CI: 0.78-1.59). Selection bias did not account for lower PCM in SC vs unSC. In PLCO, there was no PCM advantage (RR=1.09; CI: 0.87-1.36). However, contamination was high; 72% of CG had PSAS. In ERSPC, there was a reduction in PCM (RR=0.79; CI: 0.69-0.92). Staging of SC detected PC was favorable. In PLCO &amp; ERSPC, increased low/intermediate risk PCs in EGs reflect some overdiagnosis. However, there were significant reductions in high risk or metastatic PC, a hallmark of effective screening. In QT, no pt had distant metastases on repeat PSAS. In PLCO, 10-yr PC survival was ≈94% in both EG &amp; CG. Conclusions: USPSTF recommendations against PSAS are not justified. While PCM comparisons by ITT do not show that PSAS clearly saves lives, ITT analyses are biased due to compliance or contamination. Conversely, RTs demonstrate that PSAS reduces high-risk and metastatic PC. From a population perspective, there has been a dramatic 42% reduction in PCM in US between 1991-2005, largely the result of our "national experiment" in which PSAS was widely introduced. If USPSTF guidelines are implemented, PCM will likely rise in US.

Aspirin use and mortality in men with localised prostate cancer: A cohort study.

5084 Background: Cyclooxygenase-2 (COX-2) expression in prostate cancer has been associated with high grade tumours and poorer prognosis. Use of aspirin, a COX-2 inhibitor, has been associated with reduced prostate cancer mortality in some studies. These studies have not, however, provided information on the dose and timing of aspirin use. Methods: National Cancer Registry Ireland data was used to identify men with stage I-III prostate cancer (ICD10 C61) diagnosed 2001-2006. Aspirin use in the year preceding prostate cancer diagnosis was identified from linked prescription refill data (General Medical Services) and stratified by dose (low ≤75mg, high &gt;75mg) and dosing intensity (proportion of days in that year with aspirin supply available). Cox proportional hazards models, adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumour size, pre-diagnostic statin use, and receipt of radiation (time varying) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between aspirin use and all-cause and prostate cancer-specific mortality. Interactions with tumour characteristics were examined. Results: 2,936 men with stage I-III prostate cancer were identified (aspirin users, N=1,131; 38.5%). Median patient follow-up was 5.5 years. In multivariate analyses, aspirin use was not associated with a significant reduction in prostate cancer-specific (HR 0.90, 95% CI 0.68-1.20) or all-cause mortality (HR 0.98, 95% CI 0.84-1.15). In dose response analyses aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving &gt;75mg of aspirin (HR 0.59, 95% CI 0.35-1.00, p=0.048) but not ≤75mg aspirin (HR 1.01, 95% CI 0.75-1.37, p=0.938). Stronger associations were also observed in men with higher aspirin dosing intensity or a Gleason score &gt;7. Conclusions: Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving &gt;75mg of aspirin. These results confirm previous findings, and provide important new information regarding the dose of aspirin associated with survival benefit.

There are calls for a national screening programme for prostate cancer: what is the evidence to justify such a national screening programme?

Prostate cancer is the commonest cancer in men and a major health issue worldwide. Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. To assess the latest evidence regarding prostate cancer screening and whether it meets the necessary requirements to be established as a national programme for all men. Electronic databases and library catalogues were searched electronically and manual retrieval was performed. Only primary research results were used for the analysis. In recent years, several important randomised controlled trials have produced varied outcomes. In Europe the largest study thus far concluded that screening reduced prostate cancer mortality by 20%. On the contrary, a large American trial found no reduction in mortality after 7-10 years follow-up. Most studies comment on the adverse effects of screening - principally those of overdiagnosis and subsequent overtreatment. Further information about the natural history of prostate cancer and accuracy of screening is needed before a screening programme can be truly justified. In the interim, doctors and patients should discuss the risks, benefits and sequelae of taking part in voluntary screening for prostate cancer.

Does screening for prostate cancer reduce prostate cancer mortality?

Does screening for prostate cancer reduce prostate cancer mortality?

Furthering the prostate cancer screening debate (prostate cancer specific mortality and associated risks)

Screening for prostate cancer remains a contentious issue. As withother cancer screening programs, a key feature of the debate isverification of cancer-specific mortality reductions. Unfortunatelythe present evidence, two systematic reviews and six randomizedcontrolled trials, have reported conflicting results. Furthermore, halfof the studies are poor quality and the evidence is clouded by keyweaknesses, including poor adherence to screening in the interventionarm or high rates of screening in the control arm. In highquality studies of prostate cancer screening (particularly prostatespecificantigen), in which actual compliance was anticipated inthe study design, there is good evidence that prostate cancer mortalityis reduced. The numbers needed to screen are at least as goodas those of mammography for breast cancer and fecal occult bloodtesting for colo-rectal cancer. However, the risks associated withprostate cancer screening are considerable and must be weighedagainst the advantage of reduced cancer-specific mortality. Adverseevents include 70% rate of false positives, important risks associatedwith prostate biopsy, and the serious consequences of prostatecancer treatment. The best evidence demonstrates prostate cancerscreening will reduce prostate cancer mortality. It is time for thedebate to move beyond this issue, and begin a well-informed discussionon the remaining complex issues associated with prostatecancer screening and appropriate management.

The 8th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

The 8th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial

To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). A total of 141,578 men aged 55–69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC)patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre,study arm and study attendance. The excess mortality rates were compared between the two study arms. The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI]1.62–1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55–1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96–1.01). Although the reduction in excess mortality was not statistically significant, the between arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.