• 2022-08
  • 2022-07
  • 2022-05
  • 2022-04
  • 2021-03
  • 2020-08
  • 2020-07
  • 2020-03
  • 2019-11
  • 2019-10
  • 2019-09
  • 2019-08
  • 2019-07
  • br b PSA values for both races were


    b PSA values for both races were low in this DETA NONOate study, possibly due to differences in laboratory assay or storage of blood samples, which were collected in the early 1960s.
    research were not known by participants. In addition, among the 48% of men who completed follow-up ques-tionnaires approximately 4.5 yr after cohort entry and 36% who completed a second follow-up at 7.5 yr, there was no difference among controls in the prevalence of PSA testing between those with baseline PSA above or below the median.
    Sensitivity analyses support limited verification bias as we note the increased risk of PCa for men with baseline PSA well below 4.0 ng/ml, which is the cutoff that typically triggers follow-up in clinical practice. Indeed, associations remained very strong when we excluded men with baseline PSA >4 ng/ml. In addition, we observed a strong association with advanced disease which is less affected by “over-diagnosis”.
    With a median follow-up of 9 yr and maximum time between blood draw and PCa diagnosis of 12 yr, we were unable to test the longer-term ability of a single baseline PSA test to predict risk of aggressive PCa. The high ORs observed would likely be attenuated with additional follow-up as cancer is diagnosed in controls and PSA becomes less predictive over time [35]. In addition, we could not distinguish stage T3a and T3b cancers due to the level of detail available in cancer registry data for most of the men. Thus, our definition of “aggressive” disease likely includes some men with T3a disease, which is less aggressive than stage T3b. Finally, we note that many of the reported OR CIs are wide, with infinite upper limits in certain cases when there were no cases in the reference group. However, since the exact logistic regression procedures used here are known to be conservative [36], the fact that all lower limits are bounded well away from 1.00 alleviates concern of false-positive associations. 
    5. Conclusion
    PSA levels in midlife strongly predict subsequent develop-ment of aggressive PCa in a cohort of black men subject to opportunistic PSA screening. PSA levels from 1 to 3 ng/ml were indicative of large increases in risk, with few PCa cases occurring among men with levels <1 ng/ml. The totality of evidence from this study and previous work provides strong support for use of midlife PSA level to determine a personalized screening strategy.
    Author contributions: Mark A. Preston and Kathryn M. Wilson had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
    Study concept and design: Preston, Mucci, Wilson, Lilja, Kibel.
    Acquisition of data: Blot, Signorello, Steinwandel, Lilja.
    Analysis and interpretation of data: Preston, Wilson, Gerke, Blot, Markt.
    Drafting of the manuscript: Preston, Wilson, Gerke, Markt, Trinh, Carlsson.
    Critical revision of the manuscript for important intellectual content: Kibel, Vickers, Signorello, Mucci, Blot.
    Statistical analysis: Wilson, Gerke, Carlsson, Vickers, Sjoberg.
    Obtaining funding: Preston, Mucci, Lilja.
    Administrative, technical, or material support: Kibel, Lilja, Mucci.
    Supervision: Mucci, Wilson.
    Other: None.
    Financial disclosures: Mark A. Preston and Kathryn M. Wilson certify that all conflicts of interest, including specific financial interests and relation-ships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultan-cies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: SC has received a lecture honorarium and travel support from Astellas Pharma (unrelated to current study). Hans Lilja holds patents for free PSA, hK2, and intact PSA assays and is named, along with Andrew J. Vickers, on a patent application
    for a statistical method to detect prostate cancer. The marker assay patents and the patent application for the statistical model has been licensed and commercialized as the 4 K score by OPKO Diagnostics. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO.
    Funding/Support and role of the sponsor: The Southern Community Cohort Study was supported by the NIH (grant numbers R01 CA092447 and U01 CA202979). This work was supported by the Dana-Farber/ Harvard Cancer Center Mazzone Awards Program to M.A.P., the Dana-Farber/Harvard Cancer Center SPORE in Prostate Cancer to L.A.M. (P50 CA090381), Prostate Cancer Foundation Young Investigator Awards to L. A.M., M.A.P. and K.M.W., an American Urological Association Urology Care Foundation Scholar Award to M.A.P., and a post-doctoral grant from AFA Insurance to S.V.C. S.C.M. is supported in part by NIH T32 CA 009001. Additional funding support was provided from the National Cancer Institute [R33 CA127768, P50 CA92629, P30 CA008748, U01 CA199338-02]; the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Research Council [VR-MH project nr. 2016-02974], the Swedish Cancer Society [CAN 2017/559]; the Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch through the Prostate Cancer Foundation.