Refers to article:
Impact of Early Diagnosis of Prostate Cancer on Survival Outcomes
Accepted 15 January 2015
September 2015 (Vol. 1, Issue 2, pages 137 - 146)
Population-based prostate-specific antigen (PSA) screening for prostate cancer has become a heated health policy issue in recent years, and a thorough understanding of this complex narrative is essential to ensure progress and innovation as we move forward. In this issue of European Urology Focus, van den Bergh and coauthors  present an insightful review of the impact of early diagnosis of prostate cancer via PSA-based screening, and provide both a broader overview of population-based trends in disease characteristics and a nuanced analysis of the two landmark screening trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial  and the European Randomized Study of Screening for Prostate Cancer (ERSPC) .
As the authors describe, data support both a significant stage migration and a mortality reduction since the introduction of PSA screening in the 1990s. For instance, the proportion of men presenting with metastatic disease has decreased from approximately 1 in 3 in the 1980s to 4% from 2004 to 2010  and  and prostate cancer mortality has decreased, with an estimated 45–70% of the decline attributed to screening . Yet despite promising trends in population-based data, the two randomized screening trials have, at first glance, failed to demonstrate the anticipated mortality reduction: PLCO noted no benefit of screening and ERSPC revealed a mortality reduction of 21% over 13-yr follow-up. However, “absence of evidence is not evidence of absence,” and an accurate interpretation of these studies requires a more nuanced analysis. As the authors emphasize, the two studies had significant rates of contamination and noncompliance, both of which would mitigate any screening benefits. As an example, the estimated mortality reduction in ERSPC would increase to as high as 51% after accounting for both effects. Moreover, simulation data support a greater absolute mortality reduction over extended follow-up, with the number needed to treat to prevent one cancer death decreasing from 48 men at 9 yr to 9 men at 25 yr on the basis of ERSPC data .
Nonetheless, both leadtime bias and overdiagnosis are real and cannot be overlooked. Estimates vary by study, but overdiganosis may occur in as many as 50% of screen-detected cases . These “harms” of screening, coupled with a smaller than anticipated mortality reduction when applied at a population level, have led to revision of screening guidelines in both the USA and Europe  and . The repercussions of such changes can already be seen in clinical practice, with an immediate reduction in PSA screening rates for men of all ages ; however, more importantly, the long-term consequences are unknown.
Recognition of the inadequacies of population-based PSA screening represents a critical opportunity for new approaches to screening. To this end, van den Bergh and colleagues appropriately advocate a personalized approach to screening aimed at detecting clinically significant prostate cancer. They describe several potential adjuncts, including risk calculators that combine clinical and laboratory data for more comprehensive risk assessment, multiparametric magnetic resonance imaging for identification of clinically significant disease, and application of genomic data to improve the performance of PSA screening or augment risk stratification.
One additional strategy is to focus on minimizing overtreatment rather than targeting overdiagnosis, as with active surveillance (AS). AS for low-risk prostate cancer has been increasingly adopted since the early 2000s, and long-term follow-up data demonstrate very low disease-specific mortality . Such an approach attempts to strike a balance between reducing treatment-related morbidity and preserving the mortality reduction arising from screening.
Recent events may have signaled the end of indiscriminate, population-wide PSA screening, but they have also accelerated efforts to address the need for reducing prostate cancer mortality while minimizing morbidity associated with screening and treatment. Ultimately, future clinical practice will likely rely on a combination of novel, individualized screening approaches coupled with personalized treatment modalities, both aimed at realizing these goals.
Conflicts of interest
The authors have nothing to disclose.
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Department of Urology, Mayo Clinic, Rochester, MN, USA
Corresponding author. Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1 507 2669968; Fax: +1 507 2844951.
© 2015 European Association of Urology, Published by Elsevier B.V.