Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial

No AccessJournal of UrologyAdult Urology1 Oct 2023Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening TrialThis article is commented on by the following:Editorial Comment Kendrick Yim, Chaoran Ma, Sigrid Carlsson, Hans Lilja, Lorelei Mucci, Kathryn Penney, Adam S. Kibel, Scott Eggener, and Mark A. Preston Kendrick YimKendrick Yim https://orcid.org/0000-0002-4111-0279 Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts , Chaoran MaChaoran Ma Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts , Sigrid CarlssonSigrid Carlsson Departments of Surgery (Urology Service) and Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden , Hans LiljaHans Lilja Department of Pathology and Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Translational Medicine, Lund University, Malmö, Sweden , Lorelei MucciLorelei Mucci Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts , Kathryn PenneyKathryn Penney Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts , Adam S. KibelAdam S. Kibel Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts , Scott EggenerScott Eggener Department of Urology, University of Chicago, Chicago, Illinois , and Mark A. PrestonMark A. Preston *Correspondence: Brigham and Women's Hospital, Division of Urology, 45 Francis St, ASB II, 3rd Floor,Boston, MA 02115 telephone: 617-525-8274; E-mail Address: [email protected] Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts View All Author Informationhttps://doi.org/10.1097/JU.0000000000003603AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer. Materials and Methods: A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival. Results: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer for men with baseline PSA ≥2 ng/mL and percent free PSA ≤10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, P < .001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups. Conclusions: In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies. REFERENCES 1. . Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987; 317(15):909-916. Crossref, Medline, Google Scholar 2. . Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991; 324(17):1156-1161. Crossref, Medline, Google Scholar 3. . 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HL is named on a patent on assays to measure intact PSA and a patent for a statistical method to detect prostate cancer commercialized by OPKO Health (4KScore); receives royalties from sales of the test and has stock in OPKO Health; serves on SAB for Fujirebio Diagnostics Inc; and owns stock in Diaprost AB and Acousort AB. Ethics Statement: Access to the PLCO data set was approved through the National Cancer Institute Cancer Data Access System (Project ID: PLCO-825) together with the free PSA ancillary data set. Editor's Note: This article is the first of 5 published in this issue for which Category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 718 and 719. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySiemens D (2023) This Month in Adult UrologyJournal of Urology, VOL. 210, NO. 4, (573-574), Online publication date: 1-Oct-2023.Javier-DesLoges J, Bagrodia A, Crawford E and Kane C (2023) Editorial CommentJournal of Urology, VOL. 210, NO. 4, (637-638), Online publication date: 1-Oct-2023.Related articlesJournal of Urology1 Aug 2023Editorial Comment Volume 210Issue 4October 2023Page: 630-638Supplementary Materials Peer Review Report Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.Keywordsprostate-specific antigenprostatic neoplasmsbiomarkersMetrics Author Information Kendrick Yim Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts More articles by this author Chaoran Ma Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts More articles by this author Sigrid Carlsson Departments of Surgery (Urology Service) and Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden More articles by this author Hans Lilja Department of Pathology and Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Translational Medicine, Lund University, Malmö, Sweden More articles by this author Lorelei Mucci Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts More articles by this author Kathryn Penney Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts More articles by this author Adam S. Kibel Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts More articles by this author Scott Eggener Department of Urology, University of Chicago, Chicago, Illinois More articles by this author Mark A. Preston Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts *Correspondence: Brigham and Women's Hospital, Division of Urology, 45 Francis St, ASB II, 3rd Floor,Boston, MA 02115 telephone: 617-525-8274; E-mail Address: [email protected] More articles by this author Expand All Support: Funded in part through NIH/NCI Cancer Center Support Grant P30-CA008748 to Memorial Sloan Kettering Cancer Center (SC, HL). Supported in part by funding from National Institutes of Health/National Cancer Institute Grants U01-CA199338, R01-CA244948, and Swedish Cancer Society (Cancerfonden 20 1354 PjF; HL). Conflict of Interest: SC has received honoraria and travel reimbursement from Ipsen. HL is named on a patent on assays to measure intact PSA and a patent for a statistical method to detect prostate cancer commercialized by OPKO Health (4KScore); receives royalties from sales of the test and has stock in OPKO Health; serves on SAB for Fujirebio Diagnostics Inc; and owns stock in Diaprost AB and Acousort AB. Ethics Statement: Access to the PLCO data set was approved through the National Cancer Institute Cancer Data Access System (Project ID: PLCO-825) together with the free PSA ancillary data set. Editor's Note: This article is the first of 5 published in this issue for which Category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 718 and 719. 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