Advertisement
Advanced searchCitation search
Skip main navigation
You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.
Advertisement
No AccessUrology PracticePatient Care1 May 2016

Review Article: Best Evidence Regarding Contemporary Use of Prostate Cancer Biomarkers

View All Author Information
https://doi.org/10.1016/j.urpr.2015.06.012

Abstract

Introduction:

Management of prostate cancer was revolutionized by the discovery of prostate specific antigen. While prostate specific antigen is an excellent biomarker for followup after treatment, it has low specificity as a screening test and most biopsies are negative when prompted by elevated prostate specific antigen. Better prognostic biomarkers are needed to improve risk stratification to decide between treatment and observation.

Methods:

We reviewed the current evidence for and against available biomarkers, and discuss the specific contexts in which biomarkers may have greatest usefulness.

Results:

Recently introduced biomarkers attempt to improve on all aspects of the current prostate cancer management paradigm, including screening and diagnosis of disease, risk stratification and treatment allocation as well as disease monitoring after treatment.

Conclusions:

Each marker represents an important advance in 1 or more disease settings. Further studies are needed to determine the comparative effectiveness and cost-effectiveness of these biomarkers, and identify which tests or combinations are most useful and usable.

References

  • 1 : Seminal plasma protein p30: simplified purification and evidence for identity with prostate specific antigen. J Urol1990; 144: 1523. Link, Google Scholar
  • 2 : The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol1993; 150: 110. Link, Google Scholar
  • 3 : Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol2003; 169: 517. Link, Google Scholar
  • 4 : Cancer statistics, 2014. CA Cancer J Clin2014; 64: 9. Google Scholar
  • 5 : Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet2014; 384: 2027. Google Scholar
  • 6 : Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer. Eur Urol2012; 61: 455. Google Scholar
  • 7 : 20-Year outcomes following conservative management of clinically localized prostate cancer. JAMA2005; 293: 2095. Google Scholar
  • 8 : Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol2010; 28: 1117. Google Scholar
  • 9 : Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines. J Natl Compr Canc Netw2014; 12: 1211. Google Scholar
  • 10 : A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Goteborg, Sweden. BMC Med2008; 6: 19. Google Scholar
  • 11 : A four-kallikrein panel predicts prostate cancer in men with recent screening: data from the European Randomized Study of Screening for Prostate Cancer, Rotterdam. Clin Cancer Res2010; 16: 3232. Google Scholar
  • 12 : A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands. Br J Cancer2010; 103: 708. Google Scholar
  • 13 : A multicenter study of [-2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. J Urol2011; 185: 1650. Link, Google Scholar
  • 14 : Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml. J Urol2003; 170: 2181. Link, Google Scholar
  • 15 : Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study. Eur Urol2013; 63: 986. Google Scholar
  • 16 : Multicenter evaluation of the Prostate Health Index (PHI) for detection of aggressive prostate cancer in biopsy-naive men. J Urol2015; 194: 65. Link, Google Scholar
  • 17 Coding Corner: Practices Conducting New Cancer Testing and New BPH Procedures May Encounter Problems Billing for Changed or New Codes. Linthicum: American Urological Association Policy and Advocacy Brief, June 17, 2014. Google Scholar
  • 18 : Can urinary PCA3 supplement PSA in the early detection of prostate cancer?. J Clin Oncol2014; 32: 4066. Google Scholar
  • 19 : Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. J Urol2012; 188: 1726. Link, Google Scholar
  • 20 Gene-Based Tests for Screening, Detection, and/or Management of Prostate Cancer. Birmingham, Alabama: BlueCross BlueShield of Alabama, April 2014. Google Scholar
  • 21 Metamark Announces Partnership with Highmark Blue Shield to Provide Access to Comprehensive Urology Diagnostics: Sophisticated Diagnostic Tests Now Reimbursed through Highmark Blue Shield. New York: Business Wire, April 21, 2015. Google Scholar
  • 22 : Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res2007; 13: 5103. Google Scholar
  • 23 : Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol2014; 65: 534. Google Scholar
  • 24 : Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med2011; 3: 94ra72. Google Scholar
  • 25 MolDX. Available at http://www.palmettogba.com/palmetto/MolDX.nsf/DocsCatHome/MolDx. Accessed June 8, 2015. Google Scholar
  • 26 : Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol2014; 192: 1081. Link, Google Scholar
  • 27 : Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol2013; 189: 1110. Link, Google Scholar
  • 28 Local Coverage Determination (LCD): MolDX: ConfirmMDx Epigenetic Molecular Assay (L35368). Available at http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId = 35368&ContrId = 234&ver = 6&ContrVer = 1&Date = 11%2f03%2f2014&DocID = L35368&bc = AAAAAAgAAAAAAA%3d%3d&. Accessed June 8, 2015. Google Scholar
  • 29 : Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program. J Urol2010; 183: 534. Link, Google Scholar
  • 30 : Urinary TMPRSS2: ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study. Clin Cancer Res2013; 19: 2442. Google Scholar
  • 31 : Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam. Eur Urol2013; 64: 693. Google Scholar
  • 32 Punnen S, Steiner M, Zappala S et al: Among men with low-grade prostate cancer on prostate biopsy, the 4Kscore predicts the presence of more aggressive prostate cancer. Presented at annual congress of European Association of Urology, Madrid, Spain, March 20-24, 2015. Google Scholar
  • 33 : Clinical performance of serum isoform [-2]proPSA (p2PSA) and its derivatives, namely %p2PSA and PHI (Prostate Health Index) in men younger than 60 years of age: results from a multicentric European study. BJU Int2015; 115: 913. Google Scholar
  • 34 : Association of [-2]proPSA with biopsy reclassification during active surveillance for prostate cancer. J Urol2012; 188: 1131. Link, Google Scholar
  • 35 : Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol2011; 12: 245. Google Scholar
  • 36 : Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol2013; 31: 1428. Google Scholar
  • 37 : Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat Oncol Biol Phys2013; 86: 848. Google Scholar
  • 38 : Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol2014; 192: 409. Link, Google Scholar
  • 39 Rettner R: Prostate cancer: can new tests reduce unnecessary treatment? LiveScience, May 31, 2013. Google Scholar
  • 40 Proposed/Draft Local Coverage Determination (LCD): MolDX: Prolaris™ Prostate Cancer Genomic Assay (DL35629). Available at http://www.fdanews.com/ext/resources/files/10-14/10-27-14-prolaris.pdf?1413818378)(%20http://www.onclive.com/publications/oncology-business-news/2014/December-2014/Medicare-Reimburses-3-Prostate-Cancer-Diagnostic-Tests. Accessed June 8, 2015. Google Scholar
  • 41 : A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol2014; 66: 550. Google Scholar
  • 42 : A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol2015; 68: 123. Google Scholar
  • 43 : Early detection of residual prostate cancer after radical prostatectomy by an ultrasensitive assay for prostate specific antigen. J Urol1993; 149: 787. Link, Google Scholar
  • 44 : Prostate-specific antigen as a predictor of radiotherapy response and patterns of failure in localized prostate cancer. J Clin Oncol1992; 10: 1208. Google Scholar
  • 45 : A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol2015; 67: 778. Google Scholar
  • 46 : Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol2005; 23: 7005. Google Scholar
  • 47 Caffrey MK: Medicare reimburses 3 prostate cancer diagnostic tests. OncLive, January 4, 2015. Google Scholar
© 2016 by American Urological Association Education and Research, Inc.
Copyright © 2025 American Urological Association Education and Research, Inc.

COPYRIGHT AND PERMISSIONS: Urology Practice is an Official Journal of the American Urological Association Education and Research, Inc. and is published bimonthly by Wolters Kluwer Health Inc. The American Urological Association grants the Publisher full and exclusive publishing and distribution rights, worldwide, for both print and electronic media. Therefore no portions of the work(s) can be reproduced without written consent from the Publisher. Permissions and photocopying: For permission and/or rights to use content for which the copyright holder is Wolters Kluwer or the society we have partnered with the Copyright Clearance Center to provide permissions for our products through their RightsLink service, please go to the journal's website and after clicking on the relevant article, click on the Get Content & Permissions link under the Article Tools box that appears on the right side of the page. For questions about the Rightslink service, e-mail [email protected] or call 877-622-5543 (U.S. Only) or 978-777-9929. Permissions FAQs and information on authors permission requests are available at Journal Permission.

For translation rights requests, contact Translations. For license to republish and distribute requests, contact Licensing. For special projects and reprints (U.S./Canada), contact Alan Moore or [email protected]. For special projects and reprints (non-U.S./Canada), contact Avia Potashnik at [email protected] or [email protected].

PRIVACY POLICY: This page is operated by Wolters Kluwer and is subject to Wolters Kluwer Privacy Policy.
Your California Privacy Choicesopt-out icon