Benefits Of Prostate-specific Antigen Screening Research Articles

Variation in harms and benefits of prostate‐specific antigen screening for prostate cancer by socio‐clinical risk factors: A rapid review

AbstractObjectiveTo analyse the latest evidence on the relative harms and benefits of screening and diagnostic pathways with close examination of (i) men aged 50 years or older, (ii) men whose ethnicity places them at higher risk and (iii) men with a family history.MethodsWe conducted a literature search using PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases and other sources, from January 1990 to 25 January 2023. Two independent reviewers selected for randomised controlled trials (RCTs) and cohort studies which met our inclusion criteria.ResultsTwenty‐eight articles were selected, from six trials, including the Göteborg trial—reported separately from European Randomised Study of Screening for Prostate Cancer (ERSPC). Prostate‐specific antigen (PSA)‐based screening led to the increased detection of low‐grade cancer and reduction of advanced/metastatic disease but had contradictory effects on prostate cancer (PCa)‐specific mortality (no difference or reduced), possibly due to issues of contamination or compliance. Screening men from a relatively young age (50–55) reduced risk of PCa‐specific mortality in a subanalysis of an 18‐year follow‐up study and in a 17‐year cohort study from the main Göteborg trial. Moreover, one Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial analysis reported a trend of reduced risk of PCa‐specific mortality for men with a family history who were screened. [Correction added on 05 March 2024, after first online publication: “Cancer Screening Trial” has been added to the preceding sentence.] However, we did not find relevant studies for ethnicity.ConclusionUnder current UK practice, the choice to conduct a PSA test relies on a shared decision‐making approach guided by known risk factors. However, we found there was a lack of strong evidence on the harms and benefits of PSA screening by socio‐clinical risk factors and suggest further research is required to understand the long‐term impact of screening on high‐risk populations in the current diagnostic setting.

Association between prediagnostic prostate-specific antigen and prostate cancer probability in Black and non-Hispanic White men.

Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level. Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans. Self-identified race, age at first PSA test, prebiopsy PSA, age at first biopsy, smoking status, statin use, and socioeconomic factors were used as predictors. The adjusted predicted probabilities of cancer detection on first prostate biopsy from the logistic models at different PSA levels were calculated. After controlling for PSA and other covariates, Black veterans were 50% more likely to receive a prostate cancer diagnosis on their first prostate biopsy than White veterans (odds ratio [OR], 1.50; 95% CI, 1.47-1.53; p<.001). At a PSA level of 4.0ng/mL, the probability of prostate cancer for a Black man was 49% compared with 39% for a White man. This model indicated that Black veterans with a PSA of 4.0ng/mL have an equivalent risk of prostate cancer as White veterans with a PSA of 13.4ng/mL. The findings indicate that, at any given PSA level, Black men are more likely to harbor prostate cancer than White men. Prospective studies are needed to better evaluate risks and benefits of PSA screening in Black men and other high-risk populations.

Strategies to enhance the approach to prostate cancer screening of South African black men in the Free State: a Delphi study.

The incidence and mortality rates of prostate cancer (PCa) are disproportionately on the increase among South African black men. Recent studies show a greater net benefit of prostate-specific antigen screening of black men compared with the general population. There are, however, knowledge, attitude, and practice (KAP) gaps among primary healthcare providers (HCPs) and users (black men) on PCa screening. Likewise, there is a scarcity of research on strategies to address these gaps. This study sought to determine complementing strategies to enhance the approach to PCa screening of African men in the Free State, South Africa, from the perspectives of primary HCPs and users. This study utilized a three-round modified Delphi survey to achieve its aim. Consensus was determined by an a priori threshold of ≥70% of agreement. The survey involved a multidisciplinary panel of 19 experts. The consensus was reached on 34 items (strategies) to enhance the approach to PCa screening in the study setting. Community health education strategies were proffered, relating to relevant topics, methods, venues of delivery, and persons to deliver the education. Continuing education topics and methods of instruction were suggested for primary HCPs. In view of the existing KAP gaps in PCa screening among primary HCPs and users (black men), an expert consensus was determined, on complementing strategies to enhance the approach to PCa screening of South African black men in the study setting.

Evaluation of Prostate Cancer Screening Strategies in a Low-Resource, High-risk Population in the Bahamas

The benefit of prostate-specific antigen screening may be greatest in high-risk populations, including men of African descent in the Caribbean. However, organized screening may not be sustainable in low- and middle-income countries. To evaluate the expected population outcomes and resource use of conservative prostate-specific antigen screening programs in the Bahamas. Prostate cancer incidence from GLOBOCAN and prostate-specific antigen screening data for 4300 men from the Bahamas were used to recalibrate 2 decision analytical models previously used to study prostate-specific antigen screening for Black men in the United States. Data on age and results obtained from prostate-specific antigen screening tests performed in Nassau from 2004 to 2018 and in Freeport from 2013 to 2018 were used. Data were analyzed from January 15, 2021, to March 23, 2022. One or 2 screenings for men aged 45 to 60 years and conservative criteria for biopsy (prostate-specific antigen level >10 ng/mL) and curative treatment (Gleason score ≥8) were modeled. Categories of Gleason scores were 6 or lower, 7, and 8 or higher, with higher scores indicating higher risk of cancer progression and death. Projected numbers of tests and biopsies, prostate cancer (over)diagnoses, lives saved, and life-years gained owing to screening from 2022 to 2040. In this decision analytical modeling study, screening histories from 4300 men (median age, 54 years; range, 13-101 years) tested between 2004 and 2018 at 2 sites in the Bahamas were used to inform the models. Screening once at 60 years of age was projected to involve 40 000 to 42 000 tests (range between models) and prevent 500 to 600 of 10 000 to 14 000 prostate cancer deaths. Screening at 50 and 60 years doubled the number of tests but increased lives saved by only 15% to 16%. Among onetime strategies, screening once at 60 years of age involved the fewest tests per life saved (74-84 tests) and curative treatments per life saved (1.2-2.8 treatments). The findings of this decision analytical modeling study of prostate cancer screening in the Bahamas suggest that limited screening offered modest benefits that varied with screening ages and number of tests. The results can be combined with data on capacity constraints and evaluated relative to competing national public health priorities.

PD38-01 VALIDITY OF PSA SCREENING TRIALS IN A 'REAL WORLD' SETTING: A NATIONWIDE SURVEY ANALYSIS

You have accessJournal of UrologyProstate Cancer: Detection & Screening III (PD38)1 Apr 2020PD38-01 VALIDITY OF PSA SCREENING TRIALS IN A 'REAL WORLD' SETTING: A NATIONWIDE SURVEY ANALYSIS Deepansh Dalela*, Akshay Sood, Jacob Keeley, Sohrab Arora, Marcus Jamil, Chandler Bronkema, Nikola Rakic, James Peabody, Craig Rogers, Quoc-Dien Trinh, Mani Menon, and Firas Abdollah Deepansh Dalela*Deepansh Dalela* More articles by this author , Akshay SoodAkshay Sood More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Marcus JamilMarcus Jamil More articles by this author , Chandler BronkemaChandler Bronkema More articles by this author , Nikola RakicNikola Rakic More articles by this author , James PeabodyJames Peabody More articles by this author , Craig RogersCraig Rogers More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000917.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The efficacy of prostate specific antigen (PSA) screening is predicated on, amongst other factors, age and ethnicity of recipients. The goal of the current study was to compare the age and ethnicity of men undergoing PSA screening the United States (US) to those represented in the Prostate, Lung, Colorectal and Ovarian cancer (PLCO) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) trials. Such a comparison is a key to assess the external validity of these trials in the “real world” setting. METHODS: We used publicly-available data from National Health Institution Survey (NHIS) 2000-2018, the world’s oldest continuously administered survey of non-institutionalized US population. Men aged 50-74 without prior history of prostate cancer (PCa) who underwent PSA testing in the last 12 months as a part of routine test were considered to have undergone PSA screening. Age at PSA screening and self-reported ethnicity were compared with results reported in the PLCO (Andriole, NEJM 2009) and ERSPC (Schroeder, NEJM 2009) trials, using Rao-Scott Chi-Square tests. RESULTS: Overall, 10,854 (weighted n=11,257,531) men underwent annual PSA screening within the available years. The median (IQR) age for PSA screening recipients was 60.9 (55.3-66.4) years (compared to 61.7 years in ERSPC). While PLCO did not report the median age of their cohort, they reported the percentages in each age category. Interestingly, 59.2% of men were aged 60-74 in our cohort vs 68% in PLCO cohort (p<0.001). In terms of ethnicity, 1276 (weighted n=976,126; 8.7%) men in our dataset were African-American, compared to 4.4% in PLCO (p<0.001). CONCLUSIONS: Our analyses shows that compared to PLCO, US men undergoing PSA screening over the last two decades were younger and twice as likely to be African-American. Interestingly, the age distribution in NHIS was similar to men in the ERSPC study (that showed mortality benefit with PSA screening). As such, results of PLCO study may not be extrapolatable to US men, and our findings should be kept in mind when counseling men about the potential risks vs benefits of PSA screening. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e801-e801 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepansh Dalela* More articles by this author Akshay Sood More articles by this author Jacob Keeley More articles by this author Sohrab Arora More articles by this author Marcus Jamil More articles by this author Chandler Bronkema More articles by this author Nikola Rakic More articles by this author James Peabody More articles by this author Craig Rogers More articles by this author Quoc-Dien Trinh More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

PSA Screening for Prostate Cancer in Men under the Age of 65: A Review of Current Practice

Purpose: To review current practice in the use of Prostate Specific Antigen (PSA) testing and assess the overall risks and benefits of PSA testing for Adenocarcinoma of the Prostate, specifically in men under age 65, and those living with risk factors for the disease. Materials and Methods: An extensive literature review of PSA testing in various age groups was conducted with the goal being to review PSA screening trends and assess current recommendations regarding PSA Screening for Adenocarcinoma of the Prostate in various age groups, focusing on studies directed towards patients under the age of 65 and the long-term risks and benefits of PSA screening in the diagnostic algorithm. In order to reduce bias, we assessed our sources for variables such as reporting, measurement and/or selection bias. Our conclusions were then compared with current recommendations. Relevant studies with data compiled after 2004, centered around PSA screening in men under the age of 65 in general and specifically in men with risk factors for developing Adenocarcinoma of the Prostate were included. Editorials, newspaper articles and other non-scholarly and non-peer reviewed sources were automatically excluded.

Prostate-specific antigen testing for prostate cancer screening: A national survey of Canadian primary care physicians' opinions and practices.

In 2014, the Canadian Task Force on Preventive Health Care (CTFPHC) recommended against routine prostate cancer screening with the prostate-specific antigen (PSA) blood test. We surveyed Canadian primary care physicians (PCPs) to understand their opinions and attitudes towards prostate cancer screening in 2016. Twenty PCPs piloted the survey to assess its accessibility. We distributed a flyer to 19 633 PCPs as an insert in a large mailed package inviting them to attend a national meeting, and later promoted the survey at the meeting. Multinomial logistic regression models examined factors associated with agreement of key guideline statements and the overall benefit of PSA screening. A total of 1254 PCPs responded (rate of 6.4%); 54.7% of physicians aware of the CTFPHC recommendations report screening less often as a result. Overall, 55.6% of PCPs feel that the risks of PSA screening outweigh the benefits. On multivariable analysis, physicians who did not read the guidelines, did not have an academic appointment, or were in practice for over 20 years were significantly more likely to disagree with the statement that men 55-69 years old should not be screened for prostate cancer with PSA. Our national survey found that the prostate cancer screening practices of Canadian PCPs varies widely across physician demographic groups, with almost equal numbers for or against. This has significant ethical, medical, and legal implications. The poor response rate to highly incentivized survey request may suggest a reluctance or general apathy towards this subject because of the Task Force recommendations. Future efforts should provide physicians with objective guidance around PSA screening, incorporating input from all stakeholders, including PCPs, urologists, and patients.

What Have Patients Been Hearing From Providers Since the 2012 USPSTF Recommendation Against Routine Prostate Cancer Screening?

In this study we aimed to determine the relationship between prostate-specific antigen (PSA)-related information obtained from the provider and PSA test uptake. With recent focus on patient-provider communication (PC) and the guidelines recommending against PSA tests for prostate cancer (PCa), PC regarding the PSA test might affect PSA screening rates. We used the fourth edition of the Health Information National Trends Survey, a nationally-representative US survey on the use of cancer-related information. The survey was conducted in 3 cycles: October 2011 to January 2012 (cycle 1); October 2012 to January 2013 (cycle 2); September 2013 to October 2013 (cycle 3). Logistic regression was used to study the effect of PC on respondents' uptake of the PSA test. Most of the respondents were 51 to 65 years old, white, with college or higher education, were married, and had health insurance. PC regarding the PSA test greatly increased the chances of screening for PCa using the PSA test in all 3 cycles (odds ratio [OR], 2.51 [95% confidence interval (CI), 2.03-3.10] in cycle 1; OR, 3.50 [95% CI, 2.51-4.88] in cycle 2; OR, 2.69 [95% CI, 2.02-3.58] in cycle 3). Our study showed that PC increased the likelihood of patients undergoing PSA screening. In light of the 2012 US Preventive Services Task Force guidelines recommending against screening for PCa, PC seemed to have an opposite effect. Although updated PC that educates patients on the risks and benefits of PSA screening is needed, patients classically overemphasize benefits and underemphasize risks-which might increase rather than decrease PSA screening rates.

Let's Not Throw the Baby out With the Bathwater in Prostate Cancer Screening

In 2012, the United States Preventive Services Task Force recommended against prostate-specific antigen (PSA) –based screening for prostate cancer (grade D recommendation) primarily on the basis of the results of two large randomized clinical trials: the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). In the article accompanying this editorial, Shoag et al present their analysis of questionnaire data sent to a subset of participants in the prostate component of the PLCO study. They again illustrate the high contamination rate in the control arm of the study and call into question the internal validity of PLCO and, ultimately, whether the negative study finding can be used to inform the discussion around the effectiveness of PSA-based screening. The United States Preventive Services Task Force is currently in the process of updating their recommendation concerning PSA-based screening. Given the data presented by Shoag et al, the panel will have to seriously reconsider the validity of the PLCO trial in their deliberations. However, even if they were to completely discount PLCO, it is not entirely clear that the magnitude of benefit currently seen in the ERSPC trial will be enough to support a change in the recommendation. The latest report from ERSPC indicates that, with 13-year follow-up, 27 cases of prostate cancer need to be detected (NND) to prevent one prostate cancer–related death (NND). Although modeling studies extrapolating follow-up in ERSPC out to 25 years or more indicate that NND ultimately may be less than 10, these simulation studies are dependent on myriad assumptions, which may or may not prove to be true. To this end, the task force may choose to only consider the actual randomized clinical trial evidence collected from ERSPC to date, which currently indicates a small to moderate benefit at best. The documented (albeit small) benefit of PSA screening identified in ERSPC must then be weighed against the potential harms of screening. For example, an elevated PSA test often leads to a prostate biopsy. In a recent study of 1,147 men undergoing prostate biopsy in the Prostate Testing for Cancer and Treatment study, 31.8% reported grade 2 adverse events (defined as symptoms causing moderate/major problems or requiring contact with the health care system) and 1.4% required hospital admission within 30 days. Although no deaths were noted in the cohort, these adverse events undoubtedly resulted in discomfort and anxiety, with at least a temporary negative impact on overall health. Furthermore, in patients in whom prostate cancer is diagnosed and treated, both surgery and radiation are associated with a considerable risk of sexual, urinary, or bowel problems. This may be acceptable in patients with higher-risk disease, who are likely to experience a survival benefit from aggressive treatment. Given the widely recognized risk of overdiagnosis associated with population-based annual PSA screening, patients diagnosed with low-risk clinically indolent disease who elect aggressive therapy are unlikely to garner any survival advantage and are, therefore, at considerable risk of overtreatment. Recent data demonstrating increased use of active surveillance in American men diagnosed with low-risk disease is reassuring, however, as we attempt to optimize the balance of predicted benefit associated with prostate cancer treatment and the predicted morbidity of therapy. Increasing penetration of active surveillance will likely mitigate some of the risk of overtreatment, but, given ongoing challenges associated with accurately classifying indolent and clinically relevant disease, it certainly does not eliminate it. If one weighs the benefits of population-based screening seen in ERSPC (completely dismissing PLCO) against the potential harms noted in these and other studies, it is not completely unreasonable to conclude that the benefits of population-wide annual PSA screening do not outweigh the harms. Does this mean that we should abandon PSA-based screening altogether? Given the benefit seen in ERSPC, the answer is clearly no. Rather, we should focus on identifying better screening strategies that optimize the risk-benefit ratio by personalizing the approach to the target population’s underlying risk of disease. Consider that the ERSPC consisted of eight unique sites that used eight similar but distinct protocols for prostate cancer screening that varied by age of initiation, screening interval, and threshold for diagnostic biopsy. Of these eight sites, only two (Sweden and the Netherlands) noted a statistically significant difference in prostate cancer–specific survival, although the magnitude of observed differences and the size of these cohorts were sufficient to drive the results of the parent study. The observed heterogeneity in outcomes between ERSPC sites is likely the result of variation in the intensity and delivery of the intervention (PSA screening) superimposed on differences in underlying risk of disease between

The current state of prostate-specific antigen testing.

Since prostate-specific antigen (PSA) testing was approved in 1994, the incidence of metastasis and mortality from prostate cancer have significantly decreased. However, PSA screening for prostate cancer has limitations and few large randomized controlled trials have been conducted to determine the mortality benefit of PSA screening. Two studies that have been conducted are the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). These were the two main studies the US Preventive Services Task Force (USPSTF) used in its recommendation against prostate cancer screening in 2012. However, new evidence has demonstrated that the PLCO trial had significant limitations and the results of the ERSPC trial were more significant than previously thought. This article describes the strengths and weaknesses of the USPSTF's recommendation, along with current guidelines for prostate cancer screening.

All care, but whose responsibility? Community juries reason about expert and patient responsibilities in prostate-specific antigen screening for prostate cancer

General practitioners have implicitly been given responsibility for guiding men's decisions about prostate-specific antigen-based screening for prostate cancer, but patients' expectations of the bounds of this responsibility remain unclear. We sought to explore how well-informed members of the public allocate responsibilities in prostate-specific antigen screening decision-making. In 2014, we convened two Community juries in Sydney, Australia, to address questions related to the content and timing of information provision and respective roles of patients and general practitioners in screening decisions. Participants in the first jury were of mixed gender and of all ages (n = 15); the participants in the second jury were all male and of screening age (n = 12). Both juries were presented with balanced factual evidence on the harms and benefits of prostate-specific antigen screening and expert perspectives on ethico-legal aspects of consent in medical practice. In their deliberations, jurors agreed that general practitioners should take responsibility for informing men of the options, risks and benefits of prostate-specific antigen testing, but arrived at different positions on whether or not general practitioners should also guide screening decisions. Jurors also disagreed on how much and when general practitioners should provide detailed information about biopsies and treatments. These responses suggest that for prostate-specific antigen testing, there is a public expectation that both the allocation of responsibility between general practitioners and their male patients, and the level of information provided will be tailored to individual men. In the presence of expert uncertainty, a well-informed public may have reason to embrace or resist shared decision-making processes.

Association Between Older Age and Increasing Gleason Score

IntroductionIn order to help inform the discussion about the risks versus benefits of prostate cancer screening among older men, we determined whether advanced age is associated with a higher probability of harboring high-grade or high-risk disease. Patients and MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify 383,039 men diagnosed with prostate cancer in 2004-2011. The percentage of patients diagnosed with low-, intermediate-, or high-risk disease or a Gleason score of 6, 7, or 8 to 10 was calculated by age range. As a secondary analysis, we examined whether this relationship was different in 2010-2011 versus 2007-2008 (before and after the 2009 publication of screening trials). ResultsThe probability of Gleason score 8 to 10 or high-risk disease increased significantly with increasing age. The percentage of Gleason score 8 to 10 disease among men ages 50 to 54, 70 to 74, and 80 to 84 years was 8.9%, 16.2%, and 28.5%, respectively, and the percentage of high-risk disease was 14.3%, 22.4%, and 38.7% (P < .001). There were similar relationships among men with stage T1c disease. In addition, older men experienced a significant increase in the relative probability of high-risk or high-grade disease from 2007-2008 to 2010-2011. ConclusionIn this large US-based cohort, older men had a much higher probability of high-grade or high-risk prostate cancer. Physicians and patients should take into account the higher risk of more aggressive or advanced disease in older men when discussing the risks and benefits of prostate-specific antigen screening with healthy older men with a substantial life expectancy.

Prostate-Specific Antigen Screening in Prostate Cancer: Perspectives on the Evidence

Ethan BaschDespite multiple prospective clinical trials, observational stud-ies, retrospective analyses, and simulation models, intense con-troversy persists regarding the value of screening for prostate cancer with the prostate-specific antigen (PSA) test. Similar data have been used to draw conflicting conclusions, and clinical practice guidelines appear discordant on the merits of screening (1–4).Where are the areas of guideline agreement? There is general consensus that there is limited or no benefit of PSA screening among older men (ie, those aged ≥70 or 75 years) or those with limited life expectancy (ie, <10–15 years). There is agreement that there are real harms associated with downstream clinical actions taken in response to PSA screening. And there is agreement that there is overtreatment of low-grade tumors once discovered, with growing encouragement to pursue programs of active surveillance in such men, with nascent but expanding evidence in this area (5). For men considering PSA screening, an informed discussion with their provider is universally advised.Although guidelines have recently come into greater agree-ment with each other, differences do remain. In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA screening in all men (1). The American Society of Clinical Oncology followed by agreeing with this approach only for older men but advising informed decision-making in younger men (2). Subsequently, the American Urological Association substantially revised its prior recommendations by advising against screening in men aged 70 years or older as well as in those aged less than 55 years unless at high risk of disease, with informed decision-mak-ing suggested for those between the ages of 55 and 69 years (3). These recommendations are similar to those from the American College of Physicians (4,6).Why has the scientific evidence been so challenging to inter-pret? The main culprit is the history of how PSA screening evolved, without rigorous prospective evaluation of its impact on outcomes that matter to people—such as survival and quality of life. The test became widely practiced starting in the 1980s in the absence of such evidence. It has been challenging to evaluate benefits and harms on a widely practiced test. For example, the rates of PSA screening “contamination” in the no-screening control arm of the Prostate, Lung, Colorectal and Ovarian trial was estimated at approximately 70% (7 ) and in the European Randomized Study of Screening for Prostate Cancer (ERSPC) was estimated at greater than 20% (8) (although in both cases it was likely higher).Unfortunately, the current regulatory context in which molecu-lar diagnostic tests are developed still does not require the gen-eration of clinically meaningful outcomes data (also referred to as clinical utility data). As a result, there is a substantial risk that future screening tests will emerge with similar evidence challenges. Most commercially available screening tests today are developed and marketed as laboratory diagnostic tests, which have low barriers to market entry and are not required to demonstrate evidence of clinical benefit (9). Many physicians likely assume incorrectly that these tests have proven effectiveness and safety.Recent efforts have been made to strengthen methodologi-cal standards for evaluation of diagnostic tests. For example, the Patient-Centered Outcomes Research Institute (PCORI), estab-lished in 2010 by the US Patient Protection and Affordable Care Act, has established a standard that recommends to “focus studies of diagnostic tests on patient-centered outcomes, using rigorous study designs with preference for randomized controlled trials” (10). In 2013, the Center for Medical Technology Policy (CMTP) issued an Effectiveness Guidance Document similarly recommend-ing that clinical utility be assessed prospectively for new diagnostic tests (11).However, the current US regulatory framework does not have any mechanism for requiring this level of evidence for diagnostic or screen-ing tests. This is an area of urgently needed attention as countless new tests are developed and marketed to our colleagues and patients.Two perspectives on the evidence for PSA screening are pro-vided in this issue of the Journal from opposing camps on this issue, first from Dr Timothy Wilt on the hazards of PSA screen-ing and then from Dr Peter Scardino on the merits of tailored PSA screening and treatment strategies. These perspectives, and the above comments, build on an educational session at the 2013 American Society of Clinical Oncology annual meeting on this topic (12).

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.

Response to the U.S. Preventative Services Task Force Decision on Prostate Cancer Screening

The population-level data demonstrate that the inception of prostate-specific antigen (PSA) screening has lowered mortality for prostate cancer over the past 2 decades. However, more recent evidence from randomized trials has presented conflicting results regarding the benefit of PSA screening for prostate cancer mortality. Using available data, the U.S. Preventative Services Task Force recently recommended against PSA screening for prostate cancer. However, prostate cancer continues to kill over 30,000 men annually, and as such, completely abandoning screening for this disease is a disservice to many patients. Rather, the emphasis should be on utilizing evidence-based medicine to reduce overdiagnosis and overtreatment through less frequent screening for low-risk individuals or those unlikely to benefit from screening, halting further screening when appropriate, and utilizing observational strategies in patients unlikely to suffer clinically significant effects of prostate cancer over their anticipated life expectancy.

Reconciling Primary Care and Specialist Perspectives on Prostate Cancer Screening

When specialists propose screening guidelines for primary care clinicians to implement, differences in perspectives between the 2 groups can create conflicts. Two recent specialty organization guidelines illustrate this issue. The American Urological Association guideline panel and National Comprehensive Cancer Network recommend that average-risk men first be counseled about the risks and benefits of prostate-specific antigen screening for prostate cancer at age 40 rather than at the previously recommended age of 50 years. There is no direct evidence, however, that this recommendation has any impact on prostate cancer-specific mortality. To avoid distracting primary care clinicians from providing services with proven benefit and value for patients, professional organizations should follow appropriate standards for developing guidelines. Primary care societies and health care systems should also be encouraged to evaluate the evidence and decide whether implementing the recommendations are feasible and appropriate.

To Screen or Not to Screen…: a Comment on Lepore et al.

To Screen or Not to Screen…: a Comment on Lepore et al.

PSA testing in general practice

In New Zealand, prostate-specific antigen (PSA) testing has increased significantly (275 000 tests/year). Controversy exists around PSA testing as part of an unorganised screening programme. To look at the use of PSA testing in a sample of general practices and investigate the reasons GPs undertake PSA testing. Five Waikato general practices investigated looking at PSA laboratory tests of men ≥40 years in 2010 compared against GP notes. Testing rates, reasons for testing, histology and referral/s were examined for different age groups. A questionnaire was sent to the GPs to determine their views on PSA testing. One in four men aged 40+ years had a PSA test in 2010. Of these men, 71% were asymptomatic. More than half of men tested aged 70+ years were asymptomatic. Ten percent of all PSA tests were elevated. Twenty-one of 23 prostate cancers were diagnosed following an elevated PSA test: more than 80% of these men had histories of prostate pathology or lower urinary tract symptoms. The questionnaire confirmed that GPs believe in the benefits of PSA screening and it also showed they had difficulty in providing patients with information about pros and cons of PSA testing. All GPs in this study tested asymptomatic men. GPs in this study value PSA screening and believe that it reduces mortality rates. However, although PSA tests were most frequently done on asymptomatic patients, the majority of patients subsequently diagnosed with prostate cancer had been tested because of symptoms or had previous prostate problems.

Translating medical evidence to promote informed health care decisions.

To examine the effects of a community-based intervention on decisions about prostate-specific antigen (PSA) screening using multiple measures of informed decision making (IDM). Nonequivalent control group time series design collecting primary data in late 2004 and 2005. We developed a multimodal intervention designed to convey the medical uncertainty about the benefits of PSA screening and early treatment and the limited predictive ability of both the PSA test and pathological specimens collected from prostate biopsy. We examined (1) patients' recognition that there is a decision to be made about PSA screening, (2) prostate cancer knowledge levels, (3) their preferred and actual levels of participation in decision making about screening at three points in time, and (4) screening decision. Baseline data collection occurred in community-based organizations. These organizations served as recruiting sources and as sites for the intervention. We collected follow-up data by mail with telephone reminders. Our intervention was associated with greater recognition of the PSA test as a decision to be made, levels of knowledge, both preferred and actual levels of involvement in decision making, but did not have an impact on the screening decision. Community-based interventions can influence key measures of IDM about PSA screening.

Association of Insurance and Race/Ethnicity with Disease Severity among Men Diagnosed with Prostate Cancer, National Cancer Database 2004-2006

Previous studies documenting variations in severity of prostate cancer at diagnosis by race/ethnicity and insurance status have been limited to small sample sizes and patients ≥65 years of age. This study examines disease severity among patients ages 18 to 99 from the National Cancer Database (NCDB). Patients diagnosed between 2004 and 2006 with prostate cancer were selected from the NCDB (n = 312,339). We evaluated the association among three disease severity measures: prostate specific antigen (PSA) level, Gleason score 8 to 10, and clinical T-stage 3/4, by race/ethnicity and insurance while adjusting for sociodemographic and clinical factors. Uninsured and Medicaid-insured patients had elevated PSA levels, higher odds of advanced Gleason score [uninsured odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.82-2.12; Medicaid OR, 1.67; 95% CI, 1.55-1.79], and advanced clinical T stage (uninsured OR, 1.85; 95% CI, 1.69-2.03; Medicaid OR, 1.49; 95% CI, 1.35-1.63) compared with privately insured patients. Black (OR, 1.19; 95% CI, 1.15-1.23), Hispanic (OR, 1.16; 95% CI, 1.10-1.23), and Asian patients (OR, 1.22; 95% CI, 1.24-1.43) had higher odds of advanced Gleason score and similar odds of advanced stage of disease relative to whites. Insurance status is strongly associated with disease severity among prostate cancer patients. Strong associations between insurance and disease severity may be related to lack of access to preventive services such as PSA screening and barriers to medical evaluation. Although the risks and benefits of PSA screening have not been fully elucidated, it is important that all men have the opportunity to be informed about this option and preventative medical services.