The relationship between early detection of prostate cancer (PCa) and disease-specific mortality is still the subject of much debate.
This review describes developments in PCa mortality rates and disease-stage shift on a population level. The main findings from the randomised screening trials are also discussed. Finally, we consider the expected consequences for the individual man interested in screening.
The PubMed database was searched for trials of screening for PCa from inception through October 11, 2014. Supplementary information was collected by cross-referencing the reference lists.
Since the introduction of prostate-specific antigen testing, PCa incidence has risen, and a stage shift towards more favourable disease at diagnosis has been observed. PCa mortality rates are gradually decreasing. Although screening trials show conflicting results, the largest randomised trial of screening for PCa shows a 21% decrease in PCa-specific mortality. After correction for noncompliance and contamination, a risk reduction in PCa-specific mortality of up to 49% has been reported. The main side effect of screening is that some studies have estimated that approximately 50% of detected cases may represent overdiagnosis, which may be reduced by stopping screening in older men and using an individual risk-based approach.
To maximise the benefits while minimising the risk of overdiagnosis, future screening should follow an individual risk-based approach.
On a population level, the introduction of screening for prostate cancer (PCa) is associated with more men diagnosed but with more favourable disease. The largest screening study confirmed the reduction in death due to PCa. Individual risk estimation is important to best balance the benefits and potential harms of early detection.
Keywords: Prostate cancer, Screening, Early detection, Population, Survival.
Cancer screening aims to advance the moment of diagnosis to an earlier stage before the malignancy has spread, with a higher chance of successful curative treatment. In the early 1990s, it was found that screening for prostate cancer (PCa) using digital rectal examination (DRE) and prostate-specific antigen (PSA) resulted in rates of organ-confined disease of 70–85% compared with 30% in unscreened men . Different population-based randomised controlled trials (RCTs) assessed whether this favourable shift also affected PCa-specific mortality , , , , and .
As conflicting results have reported, the impact of screening on PCa-specific mortality is a subject of ongoing debate, resulting in different guidelines worldwide , , and . Screening may be performed in an organised (as mass screening of an entire population or selective screening of a specific population with an increased risk) or opportunistic fashion (on an individual basis). The balance between benefits and harms of screening may vary substantially depending on individual factors , , , , and .
This review focuses on the association between the early diagnosis of PCa and disease-specific mortality on a population level, reviews the available RCTs, and assesses the impact of early diagnosis for the individual patient.
2. Evidence acquisition
The PubMed database was searched for reports on the relationship between screening and PCa mortality at a population level, on RCTs of PCa screening, and on the consequences of screening for the individual man. The following search strategy was used (title/abstract): prostate cancer and (screening or early detection) and (mortality or survival), from inception through October 11, 2014. All English-language studies on PCa screening were considered eligible. The search strategy resulted in 1465 hits from which the most recent and relevant studies were selected based on date of publication and journal impact factor, after consensus of the three authors. Formal quality assessment was not performed. Additional articles were included after cross-referencing of the retrieved articles, resulting in a total of 61 articles selected for inclusion (11 on a population level , , , , , , , , , , and , 23 on screening trials , , , , , , , , , , , , , , , , , , , , , , and , and 27 on screening on an individual level , , , , , , , , , , , , , , , , , , , , , , , , , , and ). Figure 1 presents the search strategy flow diagram.
3. Evidence synthesis
3.1. Population level
3.1.1. Trends in prostate cancer mortality
PCa accounts for 22.8% of all cancers detected in European men and 9.5% of all cancer-related deaths . Figure 2 presents rates of death due to PCa per European region. PCa incidence and mortality rates have been changing in recent decades. In most Western countries, the incidence of PCa sharply increased after PSA became available for early detection of PCa in the early 1990s . Especially high-risk countries such as the United States, Canada, Australia, and France had a rise in incidence . Following this initial rise in incidence, the rates stabilised but have remained at higher levels than before widespread screening. The increase in PC can mainly be attributed to opportunistic screening. Only a minority of screening has been within RCTs of screening for PCa that sometimes include large areas or provinces of countries. Nationwide screening programmes are uncommon.
In many of the countries with an increase in incidence, mortality rates have also decreased. The annual percentage change in PCa mortality over the last 10 yr has been reported up to 4.0% (for Austria) . In 2014, standardised death rates for PCa were predicted to fall by 10% . Figure 3 presents the incidence and mortality rates for PCa in the Netherlands (representative of Western countries).
A recent study from Sweden compared PCa incidence and mortality rates between different regions. It found that regions with a high incidence of PCa, reflecting a high uptake of screening for PCa, had lower PCa-specific mortality rates versus regions with lower PCa screening rates (rate ratio [RR] of 0.81 for PCa-specific mortality) . It has been suggested that 45–70% of the observed declines in PCa mortality in the United States may be due to screening . Other contributing factors include improvements in PCa treatment efficacy and availability of treatment for metastatic disease.
3.1.2. Distribution of grade and stage of disease
In countries with widespread PCa screening, the mix in stage and grade at the time of diagnosis has become much more favourable over time. The proportion of men with metastatic disease at diagnosis is much lower than before early detection was widely applied. Population registries such as Cancer of the Prostate Strategic Urologic Research Endeavour and Surveillance Epidemiology and End Results (SEER) in the United States show that the proportion of non–low-risk disease decreased from 70.2% (527 of 751 cases) in 1989–1992 to 54.7% (1160 of 2119 cases) in 1999–2001 . In the 1980s, with DRE as the primary method of screening, 30–35% of patients had bone metastasis and 45–50% had nodal disease at diagnosis . In 2004, 6% of patients were diagnosed with nonlocalised disease , and the proportion of metastatic disease was down to 4% in the most recent SEER data from 2004 to 2010 .
In the National Prostate Cancer Register of Sweden, the fraction of low-risk disease doubled and the fraction of metastatic disease decreased from 25% to 11% from 1998 to 2011 (1545 and 995 cases, respectively) . Furthermore, low-risk patients today have more favourable disease than men classified in that category in the past . There has been a shift in the low-risk category towards more favourable stages (T1), lower PSAs, and less positive biopsy cores over time. Similar patterns were seen within the intermediate- and high-risk groups as well.
3.2. Screening trials
Table 1 presents the most important characteristics, interventions, and outcomes of trials of screening for PCa.
|ERSPC||Initiated 1994; n = 162; 243 men randomised; 8 European countries; core age group: 55–69 yr||PSA screening every 2–4 yr, biopsy indication ≥3.0–4.0 ng/ml, other measures such as DRE also tested||Report in 2014 : Relative risk reduction PCa-specific mortality of 21% for screening group compared with control group. Overdiagnosis estimates up to 50%.|
|PLCO||Initiated 1993; n = 76; 693 men randomised; 10 US centres; age group: 55–74 yr||PSA screening annually for 6 yr, biopsy indication ≥4.0 ng/ml, DRE for 4 yr||Report in 2012 : No significant reduction in PCa-specific mortality between screening and control group. High rates of prescreening.|
|Norrkoping||Initiated 1987; n = 9026; Sweden; age group: 50–69 yr||DRE screening in every 6th man included, PSA added later, biopsy indication >4.0 ng/ml||Report in 2011 : No significant difference in PCa-specific death between screening and control. PSA omitted initially.|
|Quebec||Initiated 1988; n = 46 486; Canada; age group: 45–80 yr||PSA screening annually, biopsy indication >3.0 ng/ml or rising 20%, and DRE||Report in 2004 : Significant reduction PCa-specific death of 62% in screening group compared with control group. High-risk (selection) bias, low rate of acceptance of screening.|
|Stockholm||Initiated 1988; n = 27 146; Sweden; age group: 55–70 yr||Onetime PSA screening, in every 10th man included, biopsy indication >10.0 ng/ml||Report in 2009 : No impact on PCa-specific death between screening and control group. Low screening frequency, high PSA threshold, and risk of bias.|
DRE = digital rectal examination; ERSPC = European Randomised Study of Screening for Prostate Cancer; PCa = prostate cancer; PLCO = Prostate, Lung, Colorectal, and Ovary cancer screening trial; PSA = prostate-specific antigen.
3.2.1. European Randomised Study of Screening for Prostate Cancer
The European Randomised Study of Screening for Prostate Cancer (ERSPC) was initiated in 1994 and randomised 162 243 men from eight European countries in the core age group of 55–69 yr between a screening protocol and a control group. The main screening protocol consisted of PSA measurements every 4 yr (lateralised six-core prostate biopsy if PSA ≥4.0 ng/ml or later ≥3.0 ng/ml), except in Sweden, where testing was done at 2-yr intervals. Other tools such as DRE and ratio of free to total PSA were also studied in the low PSA ranges. Protocols details differed between study centres .
In 2009, with a median follow-up of 9 yr after randomisation, a significant reduction of 20% in the relative risk of death from PCa was found in the screening arm as compared with the control arm . The number needed to invite (NNI) for screening was 1410, and the number needed to detect (NND) was 48 to prevent one death due to PCa.
After a median follow-up of 11 yr, the relative reduction in the risk of death from PCa in the screening group was 21% in the intention-to-treat analysis. However, the absolute risk reduction increased from 0.71 to 1.07 PCa deaths avoided per 1000 men screened, which is reflected in the lower NNI of 1055 and NND of 37 to prevent one PCa death .
In the most recent report, with 13 yr of follow-up, the relative risk reduction remained stable at 21%; however, the absolute PCa mortality reduction again increased and is currently 1.28 per 1000 men randomised, which is equivalent to 1 PCa death averted per 781 men invited (95% confidence interval [CI], 490–1929) or 1 per 27 diagnosed (95% CI, 17–66) . Longer follow-up data are needed to fully understand the impact from screening on mortality because in the latest ERSPC report, still only 21% of all men randomised have died.
The Goteborg randomised population-based PCa screening trial was initiated outside of ERSPC, but a subset of men were subsequently included in ERSPC . The study randomised 20 000 men aged 50–65 yr based on the population registry before consenting to participate. Another difference is that screening was performed every 2 yr instead of every 4 yr. The relative risk reduction, with a median follow-up of 14 yr, was 44%.
3.2.2. Prostate, Lung, Colorectal, and Ovary cancer screening trial
The Prostate, Lung, Colorectal, and Ovary (PLCO) cancer screening trial was initiated in 1993 and randomised 76 693 men aged 55–74 yr from 10 centres in the United States to receive screening or usual care . The screening protocol consisted of annual PSA screening for 6 yr (biopsy if PSA ≥4.0 ng/ml) and DRE for 4 yr.
The PLCO first reported results concurrently with ERSPC in 2009, with a median follow-up of 7–10 yr . In contrast to ERSPC, the rate of death due to PCa was not significantly different between the screening and the control group. This was not different in an update with 13 yr of follow-up .
The most important explanations for the lack of a benefit of screening in the PLCO trial versus the significant impact of screening in the ERSPC are the high rates (40–52%) of prescreening (controls who had already been screened at baseline) and contamination (screening in control group; average of 2.7 PSA tests in 6 yr in PLCO) . This is reflected in the relatively small difference in PCa incidence rates between groups in the PLCO. Other factors include poor compliance with prostate biopsy (at first screening, 40.2% complied with biopsy indication) .
3.2.3. Other trials
Although the ERSPC and PLCO are the two main RCTs of contemporary PSA-based screening, other screening studies have been reported. The Norrkoping trial included 9026 men aged 50–69 yr of which every sixth man was allocated for screening . The first rounds of screening were based on DRE; later rounds included PSA (threshold >4.0 ng/ml) when it became available. The RR for PCa-specific death in the screening group was 1.16 (95% CI, 0.78–1.73). The initial omission of PSA is the main disadvantage of this study.
The Quebec trial included 46 486 men aged 45–80 yr in whom a 2:1 randomisation for screening versus control was performed . Screening was based on annual PSA (biopsy when >3.0 ng/ml or rising >20% from last measurement) and DRE. After a median follow-up of 7.93 yr, a 62% reduction in PCa-specific death was reported in the screening group. However, the study has a relatively high risk of selection and other biases. Also, low rates of acceptance of screening were reported (23.6% in the intervention group) and the intention-to-treat principle was not used.
The Stockholm trial included 27 146 men aged 55–70 yr of whom approximately 1 in 10 was included for screening . The intervention consisted of onetime screening using PSA (biopsy if PSA >10.0 ng/ml). No impact on PCa-specific death was found (RR: 1.10; 95% CI, 0.83–1.46). The low screening frequency, high PSA threshold for biopsy, and high risk of bias are the main weak points of this study.
3.2.4. Cochrane review
A Cochrane review pooled the data on screening and PCa mortality from the five studies presented above . The combined analysis did not show a statistically significant association between screening and PCa-specific mortality (relative risk: 1.00; 95% CI, 0.86–1.17). The quality of the included studies varies enormously, and therefore it may not be appropriate to draw conclusions on the combined analysis. The Norrkoping, Quebec, and Stockholm trials all had one or more substantial methodological limitations or were not powered to address the association between screening and PCa-specific mortality. Even when combining ERSPC and PLCO, the degree of heterogeneity may still be considered unacceptable (I2 index: 80%) .
3.2.5. Assessment of cause of death
Within the two largest PCa screening trials, assessment of the cause of death (COD) is done by an independent committee consisting of experienced physicians using a predefined algorithm with access to the complete patient chart . Although more precise than using death certificates, it may still lead to misclassification of COD, for example due to the impossibility of completely blinding patient charts to randomisation status  and . Also, this method of assessment of COD does not take into account the potential impact of the screening intervention on other CODs (i.e., earlier contact with other medical specialists) .
The ERSPC trial data have also been analysed using the excess mortality method . This approach compares the overall number of deaths in the screening group with the control group. It is a measure of the deaths due to PCa (including [indirect] deaths due to screening) that occur beyond the deaths that would be predicted for the included population. In this approach it is important to correct for attendance status because men who were invited to participate but did not attend screening had almost twice the overall mortality compared with attendees (healthy-screened bias). The reduction in excess mortality was in line with the 20% reduction in PCa-specific mortality previously reported, indicating that this finding was not due to bias in ascertaining the COD .
The secondary end point of PCa metastases was also analysed using data from four ERSPC study centres . A relative reduction of 30% (hazard ratio: 0.70; 95% CI, 0.60–0.82) was found in an intention-to-screen analysis and of 42% for men who were actually screened.
3.2.6. Stage migration
PCa does not cause symptoms until a late stage, so the goal of screening is to facilitate early detection during a curable stage. Screening should therefore lead to a stage migration, in which the stage and grade of disease are more favourable than without screening .
Table 2 shows the more favourable tumour features at diagnosis for screened men compared with controls during the first screening period of the ERSPC. In the PLCO, there was much less disparity between the two arms, primarily due to the much more heavily prescreened US population , , and .
|Clinical stage T3–4, %||Gleason score >7, %|
ERSPC = European Randomised Study of Screening for Prostate Cancer; PLCO = Prostate, Lung, Colorectal, and Ovary cancer screening trial.
In line with population-based data showing a favourable stage shift over time, both the screening and controls arms of the ERSPC had an increasing proportion of T1c tumours over time. The cumulative incidence of T1c tumours increased from 28.5% to 50% in the control arm and from 47.8% to 74.9% in the screening arm between 1994 and 1998 and 2003and 2006. Tumour characteristics in the control arm had improved to such a degree that in the last period they were similar to the tumour characteristics of the screening arm in the initial screening round . Gleason scores remained similar over time but were more favourable in the screening arm (54% vs 72% Gleason score ≤6).
Active screening also results in the diagnosis of PCa that otherwise would never have surfaced during a man's lifetime. The exact rates of overdiagnosis depend on the way it is defined (eg, epidemiological criteria, pathology features), the method of calculation, and the features of the underlying study population, resulting in a wide variation in reported rates from 1.7% to 67% .
In ERSPC, the incidence of PCa after 9 yr of follow-up was 1.91 times higher in the screening arm. However, with longer follow-up, the incidence in the control group caught up while at the same time the increased incidence in the screening arm slowed down due to cessation of active screening. Correspondingly, the difference in incidence between screening and control arms decreased over time to 1.66 and 1.57 after a median of 11 and 13 yr, respectively . Longer follow-up will provide insight into the exact level of overdiagnosis due to PSA-based screening as applied in ERSPC.
In the most recent PLCO report, 1.12 times more PCa was detected in the screening arm versus the control arm . In the Cochrane meta-analysis, rates of PCa diagnosis were significantly different between arms (relative risk of PCa diagnosis with screening: 1.30; 95% CI, 1.02–1.65) .
Another method of estimating overdiagnosis is to compare the tumour characteristics of diagnosed cases with a predefined set of criteria used to define indolent disease. In radical prostatectomy series, a common pathologic definition for insignificant PCa is localised disease, Gleason score ≤6, and tumour volume <0.5 ml . Using these criteria results in estimates of overdiagnosis ranging from approximately 5% to 31.6%  and .
A third method used to estimate the rate of overdiagnosis in a screening situation is to calculate lead time . This is the interval between the moment the tumour is detected due to screening and when the same tumour would have surfaced clinically due to symptoms. The lower the stage and grade at the time of detection by screening, the longer is the lead time and vice versa. Using statistical modelling over a lifetime in the ERSPC, the lead time has been estimated at 13, 9, and 8 yr for clinical stages T1, T2, and T3 tumours, respectively, and 12, 10, and 4 yr for Gleason score <7, 7, and >7 tumours, respectively. The overall overdiagnosis rate in screen-detected tumours was estimated at 50%. The rates of overdiagnosis have been estimated at 69%, 38%, and 30% for clinical stages T1, T2, and T3 tumours, respectively, and 62%, 40%, and 8% for Gleason score <7, 7, and >7 tumours, respectively .
3.3. Consequences for the individual man
3.3.1. Noncompliance and contamination
In the screening trials, not all men carried out their study group assignments. Some men invited for screening refused (noncompliance), and “contaminators” in the control arm received screening. The result is that the benefit for an individual man who actually undergoes screening compared with an unscreened man is higher than the benefit observed in an intention-to-treat analysis of an RCT. A correction for noncompliance resulted in a relative risk reduction for PCa mortality of 27% instead of 21% for the total ERSPC study  and . In the Rotterdam section of the ERSPC, complete data on the rates of PSA testing and biopsy of men randomised to the control arm were used to perform an analysis for both noncompliance and contamination using the Cuzick method . When correcting for both protocol violations, the relative PCa-specific mortality reduction comparing a man fully screened (ie, PSA testing and biopsy done if indicated) versus a man receiving no screening at all was 0.49 (95% CI, 0.27–0.87) in favour of screening at a median follow-up of 13 yr .
3.3.2. Screening in specific groups
The benefit of screening and the risk of overdiagnosis are strongly related to age. Figure 4 presents PCa incidence and mortality by age. In the ERSPC the RR for PCa-specific mortality was not significantly different for men ages 70–75 yr at first screening (1.26; 95% CI, 0.80–1.99) . Age thresholds restricting screening among older men reduce the chance of overdiagnosis. One study suggested that restricting screening to men aged <60 yr would reduce up to 85% of overdiagnosis on a US population basis . It has recently been suggested to use age 70 as a general threshold to stop screening, as one way to reduce the harms and preserve the benefit . Modelling studies suggest that lowering the age threshold after which screening is no longer performed has a larger impact on overdiagnosis than reducing screening frequency . However, in the Swedish part of ERSPC it was found that 9 yr after termination of screening, the cancers found in the original screening and control groups were similar again . Because PCa may still be lethal in men aged >80 yr, an individual risk stratification may be preferred over a fixed age threshold to guide the discontinuation of screening, taking risk factors and comorbidity into account in addition to chronological age .
Family history is a major risk factor for PCa, with approximately a 2.5-fold increased risk for men with an affected first-degree relative . However, several studies show that family history does not mean a greater risk of aggressive disease. The Finnish part of the ERSPC found no support for selective PSA screening in patients with first-degree relatives with PCa . Indeed, lower Gleason scores were more common in this group. Family history also was not associated with prognosis after surgery, with biochemical recurrence rates of 19%, 29%, 28%, and 19% for sporadic cases, sibling pairs, hereditary cases, and high-density family members, respectively (p = 0.3) .
Age-adjusted mortality rates for US black men are approximately 2.2 times higher than for white men and up to 12.3 times higher than those of the lowest risk groups in Asia . In PLCO it was found that despite the higher risk profile, young non-Hispanic black men had 45% lower odds of repeat testing after initial screening, possibly due to differences in access to care . Still, baseline PSA was found to be a better predictor of future PCa risk and prognosis compared with race or family history  and . Overall the impact of race on the ratio of benefits to harms from screening has not been well studied because black men were not well represented in the major RCTs  and .
3.3.3. Risk-based screening
One of the suggested methods of risk-based screening is to obtain a baseline PSA at a relatively young age (in the 40s) and stratify men for future risk accordingly. Although not included in the major randomised screening trials, the baseline PSA measurement has been included in some of the guidelines on PCa screening , , and . Almost half of the future PCa deaths originated in men with a PSA >1.6 ng/ml at ages 45–49; the chance of unfavourable outcomes is very low in patients with a PSA <0.68 ng/ml . Personalised screening could potentially be applied accordingly. It should be realised, however, that considerable overlap exists between the outcomes of men in the different PSA ranges at a young age. For example, using a cut-off of 1.6 ng/ml at age 45–49 would miss half of the future PCa deaths.
Risk calculators have also been published to translate findings in screening studies to the individual at different steps in the screening process. Table 3 presents the most important available risk calculators and the risk factors that they include. In addition to PSA, factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been shown to modify risk and are important for consideration in routine practice . In the first step of the risk calculator based on ERSPC data, family history, age, and lower urinary tract symptoms can be combined to assess the risk of finding PCa. Other clinical factors such as PSA, DRE, transrectal ultrasound findings, and prostate volume can also be entered in subsequent calculators to estimate the chance of finding PCa and significant PCa at prostate biopsy . Retrospective analyses comparing a PSA-based strategy with a risk-based strategy showed that 33% of biopsies could have been avoided, and 13% of PCa cases would not have been diagnosed, of which 70% could be considered as potentially indolent .
|ERSPC 1||Family history|
|Chance PCa detection of subsequent screening|
|ERSPC 2||PSA||PCa detection at (sextant) biopsy|
Prostate volume (by TRUS or DRE)
|PCa detection at (sextant) biopsy|
Prostate volume (by TRUS or DRE)
|PCa detection at (sextant) biopsy|
|PCa detection at (sextant) biopsy|
Free-to-total PSA ratio
|PCa detection at biopsy|
DRE = digital rectal examination; ERSPC = European Randomised Study of Screening for Prostate Cancer; IPSS = International Prostate Symptom Score; LUTS = lower urinary tract symptoms; PCa = prostate cancer; PCPT = Prostate Cancer Prevention Trial; PSA = prostate-specific antigen; TRUS = transrectal ultrasound.
Other new markers have already been incorporated into risk calculators. For example, the Prostate Cancer Prevention Trial risk calculator includes inputs for markers such as free PSA, –2proPSA, and prostate cancer antigen 3 when available . The Rotterdam ERSPC has recently released a smartphone app with a risk calculator containing PSA, DRE, prostate volume, TRUS, previous biopsy history, and the Prostate Health Index to predict the risk of finding overall and significant PCa on biopsy. In the future, other markers such as intact PSA and kallikrein-related peptidase 2 may also be incorporated into multivariable tools to refine predictions on the presence of significant PCa .
3.3.4. Future of screening
The past few years have witnessed a rapid evolution in multiparametric magnetic resonance imaging (MRI), and continued expansion in the use of imaging is projected in the setting of early PCa detection . MRI-targeted biopsies show similar overall rates of detected PCa, but with a higher yield of significant PCa (33.3% vs 23.6%), and may reduce the number of low-risk cases by up to 89.4% , , and . However, more data are needed on the use of MRI in biopsy-naive patients, and many technical and logistical challenges still exist in the larger dissemination of this technology.
Genetic variables may offer another opportunity to guide the screening process or further personalise screening. PSA, for example, may be influenced by genetic factors. As such, previous studies have proposed genetic-adjusted PSA thresholds that would take these factors into consideration (ie, higher biopsy threshold for men with higher PSA based on genotype and vice versa) . Subsequent studies in US white men showed that using a genetic-adjusted threshold would reduce the number of men recommended to undergo prostate biopsy , whereas in African American men a greater number of men would have been recommended to undergo biopsy using genetic-adjusted PSA . As of now, approximately 100 single nucleotide polymorphisms (SNPs) have been identified that are associated with PCa risk . Although individual SNPs are associated with very modest increases in risk, combining multiple SNPs together results in a much greater cumulative risk . This use of SNP panels in screening is currently being tested in the so-called Stockholm-3 trial where men are being referred for biopsy on the basis of a risk prediction model based on age, SNPs, family history, and protein-based biomarkers .
There are many exciting new possibilities for greater personalisation of screening in the future. The benefit–risk ratio of these novel techniques should be studied further.
PCa screening is associated with higher incidence rates and a stage shift towards more favourable disease. Gradually decreasing PCa-specific mortality rates have been observed at the population level that are likely due in part to screening. The ERSPC showed a decrease in PCa-specific mortality but with a trade-off of cases considered to be overdiagnosis. A risk-based approach in the individual man interested in screening may optimise the balance between benefits and harms.
Author contributions: Roderick C.N. van den Bergh had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: van den Bergh, Loeb, Roobol.
Acquisition of data: van den Bergh, Loeb, Roobol.
Analysis and interpretation of data: van den Bergh, Loeb, Roobol.
Drafting of the manuscript: van den Bergh.
Critical revision of the manuscript for important intellectual content: Loeb, Roobol.
Statistical analysis: None.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: Loeb, Roobol.
Other (specify): None.
Financial disclosures: Roderick C.N. van den Bergh certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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a Department of Urology, University Medical Centre, Utrecht, The Netherlands
b Department of Urology and Population Health, New York University, New York, NY, USA
c Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands
Corresponding author. Homeruslaan 24-1, 3581 MH Utrecht, The Netherlands. Tel. +31 6 23456800.
© 2015 European Association of Urology, Published by Elsevier B.V.