Advertisement

PSA

  • James L. Gulley
Reference work entry

Abstract

Prostate-specific antigen (PSA) is a 34-kDa tissue kallikrein glycoprotein that is expressed in normal prostate tissue and prostate cancer. This androgen-regulated serine protease aids in the liquefaction of seminal coagulum to allow sperm to become more motile. Normally, PSA is secreted into the prostatic ducts; however, in prostate cancer the disordered glandular architecture causes increased amounts of PSA to diffuse into the serum. PSA measurements serve as screening and prognostic markers for prostate cancer. PSA is also the most sensitive and widely used marker of response to therapy in patients with prostate cancer. PSA has been shown to be immunogenic. It is essentially expressed only in the prostate, therefore therapeutic targeting of PSA may be beneficial. Because it is secreted and not membrane bound, antibody approaches hold no utility. However T-cell based approaches such as therapeutic vaccines have been developed and have shown safety and preliminary evidence of efficacy in randomized studies. A definitive phase III study of PSA-TRICOM (PROSTVAC) may have results as early as the end of 2016.

Keywords

American Society for Radiation Oncology (ASTRO) Prostate-specific antigen (PSA) Androgen-deprivation therapy Assessment Biochemical failure Biology Clinical studies Preclinical models Pretreatment Risk stratification and prognosis Screening tests Therapeutics Tumor-associated antigens (TAAs) 

References

  1. Andriole GL, Crawford ED, Grubb 3rd RL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aragon-Ching JB, Jain L, Gulley JL, et al. Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer. BJU Int. 2009;103(12):1636–40.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Arlen PM, Bianco F, Dahut WL, et al. Prostate Specific Antigen Working Group guidelines on prostate-specific antigen doubling time. J Urol. 2008;179(6):2181–5. discussion 5-6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol. 2003;21(2):383–91.CrossRefPubMedGoogle Scholar
  5. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999;17(11):3461–7.CrossRefPubMedGoogle Scholar
  6. Correale P, Walmsley K, Nieroda C, et al. In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst. 1997;89(4):293–300.CrossRefPubMedGoogle Scholar
  7. D’Amico AV, Whittington R, Malkowicz SB. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280(11):969–74.CrossRefPubMedGoogle Scholar
  8. D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004;351(2):125–35.CrossRefPubMedGoogle Scholar
  9. D’Amico AV, Renshaw AA, Sussman B, Chen MH. Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy. JAMA. 2005;294(4):440–7.CrossRefPubMedGoogle Scholar
  10. D’Amico AV, McLeod DG, Carroll PR, Cullen J, Chen MH. Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality. Cancer. 2007;109(7):1290–5.CrossRefPubMedGoogle Scholar
  11. Dixon SC, Knopf KB, Figg WD. The control of prostate-specific antigen expression and gene regulation by pharmacological agents. Pharmacol Rev. 2001;53(1):73–91.PubMedGoogle Scholar
  12. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294(4):433–9.CrossRefPubMedGoogle Scholar
  13. Gann PH, Ma J, Catalona WJ, Stampfer MJ. Strategies combining total and percent free prostate-specific antigen for detecting prostate cancer: a prospective evaluation. J Urol. 2002;167(6):2427–34.CrossRefPubMedGoogle Scholar
  14. Gulley J, Chen AP, Dahut W, et al. Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer. Prostate. 2002;53(2):109–17.CrossRefPubMedGoogle Scholar
  15. Gulley JL, Arlen PM, Bastian A, et al. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res. 2005;11(9):3353–62.CrossRefPubMedGoogle Scholar
  16. Gulley JL, Arlen PM, Madan RA, et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. 2010;59(5):663–74.CrossRefPubMedGoogle Scholar
  17. Hussain M, Tangen CM, Higano C, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006;24(24):3984–90.CrossRefPubMedGoogle Scholar
  18. Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099–105.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kattan MW, Cuzick J, Fisher G, et al. Nomogram incorporating PSA level to predict cancer-specific survival for men with clinically localized prostate cancer managed without curative intent. Cancer. 2008;112(1):69–74.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Lechleider RJ, Arlen PM, Tsang KY, et al. Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant. Clin Cancer Res. 2008;14(16):5284–91.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Madan RA, Gulley JL, Arlen PM. PSA-based vaccines for the treatment of prostate cancer. Expert Rev Vaccines. 2006;5(2):199–209.CrossRefPubMedGoogle Scholar
  22. McNeel DG, Nguyen LD, Ellis WJ, Higano CS, Lange PH, Disis ML. Naturally occurring prostate cancer antigen-specific T cell responses of a Th1 phenotype can be detected in patients with prostate cancer. Prostate. 2001;47(3):222–9.CrossRefPubMedGoogle Scholar
  23. Prostate cancer nomograms: a tool for doctors and patients. Memorial Sloan-Kettering Cancer Center. 2016; http://www.mskcc.org/mskcc/html/10088.cfm.
  24. Rodrigues NA, Chen MH, Catalona WJ, Roehl KA, Richie JP, D’Amico AV. Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer. Cancer. 2006;107(3):514–20.CrossRefPubMedGoogle Scholar
  25. Scher HI, Eisenberger M, D’Amico AV, et al. Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 2004;22(3):537–56.CrossRefPubMedGoogle Scholar
  26. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320–8.CrossRefPubMedGoogle Scholar
  27. Terasawa H, Tsang KY, Gulley J, Arlen P, Schlom J. Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antigen. Clin Cancer Res. 2002;8(1):41–53.PubMedGoogle Scholar
  28. The Partin tables. James Buchanan Brady Urological Institute, Johns Hopkins Medicine. Available from: 2016; http://urology.jhu.edu/prostate/partintables.php.
  29. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med. 2004;350(22):2239–46.CrossRefPubMedGoogle Scholar
  30. Walz J, Haese A, Scattoni V, et al. Percent free prostate-specific antigen (PSA) is an accurate predictor of prostate cancer risk in men with serum PSA 2.5 ng/mL and lower. Cancer. 2008;113(10):2695–703.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, New York (outside the USA) 2017

Authors and Affiliations

  1. 1.Genitourinary Malignancies BranchNational Cancer Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations