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  • br Patient summary Prostate specific antigen


    Patient summary: Prostate-specific antigen (PSA) level during midlife strongly pre-dicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk.
    © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    1. Introduction
    The United States Preventive Services Task Force (USPSTF) recently updated their evaluation of prostate-specific antigen (PSA) screening for prostate cancer (PCa) to a “C” grade, recommending that physicians selectively provide PSA testing to individual patients based on professional judgment and patient preferences [1]. This is based on evidence that screening reduces PCa mortality but at the cost of significant over-diagnosis and over-treatment. This C recommendation applies to the general US population, including black men, who suffer a higher burden of disease [2,3]. However, the USPSTF noted an absence of direct evidence on the benefits and harms of screening in this high-risk Y-27632 and recommended that research on screening in African-American men should be a national priority.
    Risk-stratified screening targeting men at higher risk of aggressive PCa could capture much of the benefit of population-wide screening while reducing over-diagnosis. One approach to targeted screening is to use a baseline PSA measured during midlife to estimate risk and determine the frequency of further screening, with more frequent screening among men with high baseline PSA and minimal to no further testing for men with the lowest levels [4,5]. This strategy is based on the natural history of the disease; autopsy studies show that PCa begins early in adulthood, with significant rates of cancer in men in their 30s and is even more pronounced in black men [6,7]. Thus, PSA levels measured in midlife may reflect early stages of the disease process while being less prone to elevation due to benign prostatic hyperplasia (BPH) than levels later in life [8].
    Multiple studies of this baseline PSA strategy in the US [2,9–13] and Sweden [14–17], have shown that baseline PSA levels at age 40–60 yr strongly predict PCa incidence and mortality over several decades among primarily white men. To date, there have been only two studies of baseline PSA levels and subsequent aggressive PCa risk among black men [9,11].
    In this context, we undertook a nested case-control study among black men in the Southern Community Cohort Study (SCCS) to determine whether baseline PSA levels in midlife predicted future risk of PCa, with a focus on aggressive disease, as this is the most clinically relevant and less likely to be over-diagnosed. 
    2. Materials and methods
    2.1. Study population
    The National Cancer Institute-funded SCCS was established in 2001 to address and identify the underlying causes of cancer health disparities. This prospective cohort of 86 000 men and women from the southeastern US has the highest representation of African-Americans (n = 22 905 men) among existing cohorts and has a large biorepository [18]. We performed a nested case-control study of incident PCa including 766 men selected from among 10 504 black men aged 40–64 yr at study entry during 2002–2009 who gave blood at enrollment, were free of diagnosed cancer at enrollment, and provided informed consent. Recruitment took place at community health centers across 12 southern states. This project was approved by the SCCS Data and Biospecimen Use Committee and the Brigham and Women's Hospital's Institutional Review Board.
    2.2. Identification of PCas and deaths
    Incident PCa among cohort members was identified through linkage with state cancer registries. Although linkage and reporting lags are common, the registries provide nearly complete (>90%) and unbiased ascertainment of cancers diagnosed among the participants after their entry into the SCCS [18]. We identified 197 incident PCa cases through 2015, 91 of whom had aggressive disease (Gleason 7 [n = 75], American Joint Committee on Cancer (AJCC) stage III or IV [n = 26], or PCa-specific death [n = 16]; stage was available for 83% of cases, and grade was available for 70% of cases). We identified deaths attributed to PCa as those with underlying cause of death coded as ICD-9-CM 185 or ICD-10 C61. For each case, up to three controls who were alive without a PCa diagnosis at the case's diagnosis date were selected by incidence density sampling, matching on age ( 1 yr), study site, and date of blood draw ( 1 yr), resulting in 197 PCa cases and 569 controls for this analysis. For the analysis of aggressive cancer, we included only controls who were alive and free of aggressive PCa at the date of the case's “aggressive-defining” event (advanced stage or high-grade at diagnosis or PCa death). Five of the 91 aggressive cases were defined as aggressive based only on death from PCa, and we excluded three controls who were not alive at time of their matched case's death.