Although prostate-specific antigen (PSA) screening has improved the detection of prostate cancer, allowing for stage migration to less advanced disease, the precise mortality benefit of early detection is unclear. This is in part due to a discrepancy between the two large randomized controlled trials comparing PSA screening to usual care. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a survival benefit to screening, while the United States Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial did not. Furthermore, the benefit of immediate surgical intervention for screen-detected prostate cancer is unclear, as the results superficially differ between the two large randomized controlled trials comparing prostatectomy to observation. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found no survival benefit for prostatectomy in PSA screened U.S. men, while the Scandinavian Prostate Cancer Group Study Number Four (SPCG-4) found a survival benefit for prostatectomy in clinically diagnosed prostate cancer. As a result of the controversy surrounding PSA screening and subsequent prostate cancer treatment, guidelines vary widely by organization.

Serum prostate-specific antigen (PSA) testing is a simple and effective method for diagnosing prostate cancer. The widespread PSA screening resulted in increased diagnosis of early-staged, localized prostate cancer and marked reduction in advanced, metastatic cancer, which contributed to subsequent reduction in prostate cancer mortality. Most patients with localized prostate cancer, especially low-grade cancer, have an indolent clinical course. In addition, the rate of death from prostate cancer itself is very low. Therefore, early diagnosis of prostate cancer can lead to overdiagnosis and overtreatment. There has been a controversy regarding the effect of PSA screening on prostate cancer mortality. Results of the two largest randomized trials concerning PSA screening were totally contrary. European countries-based trial showed a significant prostate cancer mortality reduction, whereas the USA-based trial showed no benefit in reducing prostate cancer mortality. In 2013, based on these arguments, the American Urological Association updated a guideline regarding PSA screening, which did not recommend routine PSA screening but a selective screening, according to patient's age, coexisting medical condition, and risks, such as family history. The guideline also emphasized shared decision making.

PSA screening remains highly controversial due to several important disadvantages. More PSA is produced with prostatic enlargement and in other benign conditions such as urinary tract infections. False positive tests can then lead to unnecessary diagnostic workup with invasive prostate biopsy. Another major problem with screening programs in general is overdiagnosis of cancers that would not have caused harm during the patient's lifetime. For example, many prostate cancers have a relatively indolent behavior so may not require diagnosis or treatment in a patient with limited life expectancy. All forms of prostate cancer treatment have potential urinary and sexual side effects, so reducing overdiagnosis and overtreatment are critical public health issues. Because screening has many proven benefits but also significant harms, there are widely disparate guidelines on prostate cancer screening from major organizations worldwide. This issue of the Urologic Clinics will provide insights into the many different prostate cancer guidelines and related policy issues.

We created the You Decide multimodal intervention to provide men with the information, skills, and reinforcement needed to engage in informed decision making (IDM) related to prostate cancer screening. We developed intervention materials based on three rounds of formative research conducted with 145 members of the intended recipient audience through 10 focus groups and more than 50 individual in-depth interviews. This report documents key findings from our formative research that may apply to the development of other IDM interventions, especially those related to prostate cancer. Our findings underscored (1) the difficulty of promoting IDM for cancer screening given people's high affinity for such screenings, and (2) the challenge of graphically communicating risk-related tradeoffs. We found that pretest participants had a preference for full-story narratives conveying personal experiences and interpersonal learning opportunities. Our formative research findings also supported the need to use plain language to address a range of health literacy levels. We describe our efforts to apply these formative research findings in our final intervention materials and discuss implications for future intervention research. Our findings underscore the importance of involving the intended audience in the process of developing intervention materials.

Carcinoma of the prostate increasingly dominates the attention of urologists for both scientific and clinical reasons. The search for an explanation and the prediction of the variable behaviour of the malignant prostatic cell continues unabated. The search for more precise tumour staging and more effective treatment is equally vigorous. Editors Andrew Bruce and John Trachtenberg have assembled acknowledged leaders in prostate cancer to present those areas of direct interest to the clinician. There are a number of other topics that might have been considered but most of these, such as experimental tumour models or biochemical factors affecting cell growth, still lack immediate application for the clinician. Carcinoma of the prostate continues to have its highest incidence in the western world, and the difference in comparison with the incidence in the Far East appears to be real and not masked by diagnostic or other factors. A number of other epidemiological aspects need careful analysis: Is the incidence increasing? Is the survival improving? Is the prognosis worse in the younger patient? Epidemiological data are easily misused and misinterpreted so that a precise analysis of the known facts makes an important opening chapter to this book.

BACKGROUND: In 2008, the U.S. Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for prostate cancer in men younger than age 75 years. The USPSTF recommended against screening for prostate cancer in men aged 75 years or older. PURPOSE: To update a previous systematic review performed for the USPSTF and evaluate new evidence on the potential benefits of prostate-specific antigen (PSA)-based screening for prostate cancer. DATA SOURCES: English-language articles identified in PubMed and the Cochrane Library (search dates January 2007 to July 2011), reference lists of retrieved articles, and expert suggestions. STUDY SELECTION: Randomized controlled trials, systematic reviews, and meta-analyses were selected to determine whether PSA-based screening decreases prostate cancer-specific or all-cause mortality. Where available, information on the potential harms of screening for prostate cancer was also extracted from included studies. DATA EXTRACTION: Studies were reviewed, abstracted, and rated for quality, using predefined USPSTF criteria. DATA SYNTHESIS: Five randomized controlled trials (two fair- and three poor-quality) and two meta-analyses evaluating the impact of PSA-based screening on prostate cancer mortality were identified. A report describing results from a single center participating in one of the fair-quality trials was also identified. Of the two highest-quality trials, the U.S. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found no statistically significant effect of PSA-based screening on prostate cancer mortality after 10 years (rate ratio [RR], 1.11 [95% CI, 0.83-1.50]). The European Randomized Study of Screening for Prostate Cancer also found no statistically significant effect in all enrolled men (ages 50-74 years) after a median followup of 9 years (RR, 0.85 [95% CI, 0.73-1.00]), but reported a 0.07% absolute risk reduction in a prespecified subgroup of men aged 55 to 69 years (RR, 0.80 [95% CI, 0.65-0.98]). Neither meta-analysis indicated a reduction in prostate cancer mortality with the use of PSA-based screening. When a benefit was found, PSA-based screening resulted in an estimated 48 additional men being treated for each prostate cancer death that was averted. Twelve percent to 13% of screened men had false-positive results after 3 to 4 screening rounds, and clinically important infections, bleeding, or urinary retention occurred after 0.5%-1.0% of prostate biopsies. LIMITATIONS: Evidence was conflicting regarding the effect of screening on prostate cancer mortality in the highest-quality trials; they also represented interim results. We restricted the search on the potential harms of PSA-based screening to information available from randomized efficacy trials. CONCLUSIONS: After about 10 years, PSA-based screening results in the detection of more cases of prostate cancer, but small to no reduction in prostate cancer-specific mortality.

Essay 1: A Dynamic Model for Understanding Long-Term Trends in Prostate Cancer Screening Cancer remains the second leading cause of death in the U.S. after heart disease. After 35 years of routine cancer screening, we still have only a limited understanding of screening dynamics. There is evidence of over-screening and resulting overtreatment in certain cases, and significant provider variation and fluctuations over time in screening criteria. Here I present empirical data for fluctuations in official screening guidelines and in actual practice for the use of the prostate-specific antigen (PSA) test. I explore how these dynamics are affected by the main guideline-issuing organizations in the U.S. and by clinicians, patient groups, and the media. Essay 2: Our Walk to the End of Cancer? Understanding Long-Term Trends in Medical Screening In this study we develop the first integrated, broad boundary feedback theory and formal model to explain the dynamics of medical screening. The theory includes a decision-theoretic core around harms and benefits including the fundamental tradeoff between sensitivity and specificity; and feedbacks that condition guidelines and actual practice. To provide context we use the case of PSA screening for prostate cancer as a motivating example, but our model is generic and applicable to other contexts. We present a behaviorally realistic, boundedly-rational model of detection and selection for health screening that creates oscillations in policy recommendation thresholds of formal guidelines. This core model, entailing only the evidence generation and translation processes, demonstrates how oscillations are natural to this category of problems due to inherent delays in evidence-based screening. These fluctuations lead to long periods during which screening guidelines are suboptimal. Essay 3: A Dynamic Model for Understanding Long-Term Trends in Prostate Cancer Screening Whereas guidelines for routine screening should be based on medical evidence, evidence often has relatively little impact on practice. This situation has led to ongoing controversy and conflict over appropriate guidelines among scientists, clinicians, and patient advocacy groups. There are significant variations in clinical practice, including evidence of over-screening for some diseases, and under-screening for others. To explain the patterns of over-screening, fluctuations, low adherence to guidelines, and conflict, I develop the first explicit broad boundary feedback theory of the dynamics of medical screening, tested in a formal mathematical model. The model presents an extended case study specific to PSA screening for prostate cancer, including realistic presentations for the fundamental tradeoff between test sensitivity and specificity, the natural progression of the disease, and respective changes in population size and composition.

Prostate cancer is by far the most common cancer in men and the second leading cause of death due to cancer. It comprises a mixed group of tumours displaying varying clinical behaviour: while some have a very aggressive course, others are rather indolent. Prevention of prostate cancer and discrimination between aggressive and indolent forms are important clinical goals and the acquisition of significant new evidence on means of achieving these aims makes this book particularly timely. A wide range of topics are covered by leading authorities in the field. The biology and natural history of prostate cancer are reviewed and the role of lifestyle and dietary factors, assessed. Detailed attention is paid to risk prediction biomarkers and to the role of novel high-throughput nucleic acid-based technologies in improving risk prediction and thereby allowing tailored approaches to cancer prevention. Potential means of chemoprevention of prostate cancer are also reviewed in depth, covering the very positive new data on the impact of aspirin as well as evidence regarding 5α-reductase inhibitors, DFMO and lycopene. Guidance is provided on the differentiation of aggressive from indolent disease and the policy and research implications of recent findings are examined. This book will be of interest to both clinicians and researchers.

PSA screening remains highly controversial due to several important disadvantages. More PSA is produced with prostatic enlargement and in other benign conditions such as urinary tract infections. False positive tests can then lead to unnecessary diagnostic workup with invasive prostate biopsy. Another major problem with screening programs in general is overdiagnosis of cancers that would not have caused harm during the patient's lifetime. For example, many prostate cancers have a relatively indolent behavior so may not require diagnosis or treatment in a patient with limited life expectancy. All forms of prostate cancer treatment have potential urinary and sexual side effects, so reducing overdiagnosis and overtreatment are critical public health issues. Because screening has many proven benefits but also significant harms, there are widely disparate guidelines on prostate cancer screening from major organizations worldwide. This issue of the Urologic Clinics will provide insights into the many different prostate cancer guidelines and related policy issues.

The prostate specific antigen (PSA) test, used for monitoring treatment of prostate cancer and for cancer screening, has a number of problems including false positives and inability to distinguish those cancers that will be fatal from those that will not. This document presents guidelines that define the circumstances under which it is appropriate to use the PSA test. The guidelines are intended as a decision-making tool for prostate cancer screening and case finding.