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Twenty Years and Counting: Is PSA Still Useful in 2010?

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Management of Prostate Cancer

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

Prostate-specific antigen (PSA) has been accepted as a useful tumor marker for early diagnosis, staging, follow-up, and response to therapy of prostate cancer patients. In the last 20 years, widespread use of PSA testing has led to a remarkable increase in the incidence of prostate cancer, detection of the disease in early stages, and a reduction in mortality. Regardless of its impressive performance in the management of prostatic diseases, PSA testing has several limitations. PSA is an organ-specific marker but not disease specific. Therefore, PSA levels of men with or without prostate cancer can overlap especially in the range of 4.0–10.0 ng/mL. On the other hand, a significant number of men with PSA levels of less than 4.0 ng/mL have been diagnosed with prostate cancer. To overcome these limitations and improve the specificity of PSA testing, several molecular derivatives and isoforms have been identified. Another issue in question is the value of PSA screening and the overdiagnosis of potentially indolent cancer. Recently, the effect of PSA screening on prostate cancer mortality has been evaluated in two large prospective randomized trials, which will be discussed in detail. The following chapter will focus on the current status of PSA testing as a screening tool and recent progress to improve the utility of this marker for detection, staging, and follow-up of prostate cancer patients.

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References

  1. Jemal A, Siegel R, Xu J, et al. Cancer statistics 2010. CA Cancer J Clin. 2010;60(5):277–300.

    Article  PubMed  Google Scholar 

  2. Legler JM, Feuer EJ, Potosky AL, et al. The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence in the United States. Cancer Causes Control. 1998;9(5):519–27.

    Article  PubMed  CAS  Google Scholar 

  3. Loeb S, Catalona WJ. Prostate-specific antigen in clinical practice. Cancer Lett. 2007;249:30–9.

    Article  PubMed  CAS  Google Scholar 

  4. Ablin RJ, Bronson P, Soanes WA, et al. Tissue- and species-specific antigens of normal human prostatic tissue. J Immunol. 1970;104(6):1329–39.

    PubMed  CAS  Google Scholar 

  5. Hara M, Koyanagi Y, Inoue T, et al. Some physico-chemical characteristics of “γ-seminoprotein”, an antigenic component specific for human seminal plasma. Nihon Hoigaku Zasshi. 1971;25(4):322–4.

    PubMed  CAS  Google Scholar 

  6. Wang MC, Valenzuela LA, Murphy GP, et al. Purification of a human prostate specific antigen. Invest Urol. 1979;17(2):159–63.

    PubMed  CAS  Google Scholar 

  7. Stamey TA, Yang N, Hay AR, et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987;317(15):909–16.

    Article  PubMed  CAS  Google Scholar 

  8. Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991;324(17): 1156–61.

    Article  PubMed  CAS  Google Scholar 

  9. Brawer MK, Chetner MP, Beatie J, et al. Screening for prostatic carcinoma with prostate specific antigen. J Urol. 1992;147(3 Pt 2):841–5.

    PubMed  CAS  Google Scholar 

  10. Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol. 2003;21(2):383–91.

    Article  PubMed  CAS  Google Scholar 

  11. Avgeris M, Mavridis K, Scorilas A. Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies. Biol Chem. 2010;391(5):505–11.

    Article  PubMed  CAS  Google Scholar 

  12. Darson MF, Pacelli A, Roche P, et al. Human glandular kallikrein 2 expression in prostate adenocarcinoma and lymph node metastases. Urology. 1999;53(5): 939–44.

    Article  PubMed  CAS  Google Scholar 

  13. Lilja H, Christensson A, Dahlen U, et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha-1-antichymotrypsin. Clin Chem. 1991;37(9):1618–25.

    PubMed  CAS  Google Scholar 

  14. Zhou AM, Tewari PC, Bluestein BI, et al. Multiple forms of prostate-specific antigen in serum: differences in immunorecognition by monoclonal and polyclonal assays. Clin Chem. 1993;39(12):2483–91.

    PubMed  CAS  Google Scholar 

  15. Partin AW, Piantadosi S, Sanda MG, et al. Clearance rate of serum-free and total PSA following radical retropubic prostatectomy. Prostate Suppl. 1996;7:35–9.

    Article  PubMed  CAS  Google Scholar 

  16. Mikolajczyk SD, Grauer LS, Millar LS, et al. A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology. 1997;50: 710–4.

    Article  PubMed  CAS  Google Scholar 

  17. Mikolajczyk SD, Millar LS, Wang TJ, et al. A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. Cancer Res. 2000;60: 756–9.

    PubMed  CAS  Google Scholar 

  18. Mikolajczyk SD, Marker KM, Millar LS, et al. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res. 2001;61:6958–63.

    PubMed  CAS  Google Scholar 

  19. Catalona WJ, Bartsch G, Rittenhouse HG, et al. Serum proprostate 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 Urol. 2003;170:2181–5.

    Article  PubMed  CAS  Google Scholar 

  20. Nurmikko P, Pettersson K, Piironen T, et al. Discrimination of prostate cancer from benign disease by plasma measurement of intact free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146. Clin Chem. 2001;47(8):1415–23.

    PubMed  CAS  Google Scholar 

  21. Mikolajczyk SD, Millar LS, Wang TJ, et al. “BPSA”, a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. Urology. 2000;55:41–5.

    Article  PubMed  CAS  Google Scholar 

  22. Steuber T, Niemela P, Haese A, et al. Association of free-prostate specific antigen subfractions with volume of benign and malignant prostatic tissue. Prostate. 2005;63(1):13–8.

    Article  PubMed  CAS  Google Scholar 

  23. Djavan B, Remzi M, Zlotta AR, et al. Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: results of the prospective multicenter European trial. Urology. 2002;60(4 Suppl 1):4–9.

    Article  PubMed  Google Scholar 

  24. Partin AW, Brawer MK, Bartsch G, et al. Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial. J Urol. 2003;170(5):1787–91.

    Article  PubMed  Google Scholar 

  25. Sözen S, Eskicorapci S, Küpeli B, et al. Complexed prostate specific antigen density is better than the other PSA derivatives for detection of prostate cancer in men with total PSA between 2.5 and 20 ng/ml: results of a prospective multicenter study. Eur Urol. 2005;47(3):302–7.

    Article  PubMed  Google Scholar 

  26. Parekh N, Lin Y, Marcella S, et al. Associations of lifestyle and physiologic factors with prostate-specific antigen concentrations: evidence from the National Health and Nutrition Examination Survey (2001–2004). Cancer Epidemiol Biomarkers Prev. 2008;17: 2467–72.

    Article  PubMed  CAS  Google Scholar 

  27. Nadler RB, Humphrey PA, Smith DS, et al. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol. 1995;154(2 Pt 1):407–13.

    PubMed  CAS  Google Scholar 

  28. Leibovici D, Zisman A, Chen-Levyi Z, et al. Elevated PSA serum levels after intravesical instillation of Bacillus Calmette-Guerin. J Urol. 2000;164:1546–9.

    Article  PubMed  CAS  Google Scholar 

  29. Chybowski FM, Bergstralh EJ, Oesterling JE. The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study. J Urol. 1992;148:83–6.

    PubMed  CAS  Google Scholar 

  30. Heidenreich A, Vorreuther R, Neubauer S, et al. The influence of ejaculation on serum levels of prostate specific antigen. J Urol. 1997;157:209–11.

    Article  PubMed  CAS  Google Scholar 

  31. Oesterling JE, Rice DC, Glenski WJ. Effect of cystoscopy, prostate biopsy, and transurethral resection of prostate on serum prostate-specific antigen concentration. Urology. 1993;42(3):276–82.

    Article  PubMed  CAS  Google Scholar 

  32. Yuan JJ, Coplen DE, Petros JA, et al. Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels. J Urol. 1992;147:810–4.

    PubMed  CAS  Google Scholar 

  33. Gormley GJ, Ng J, Cook T, et al. Effect of finasteride on prostate-specific antigen density. Urology. 1994;43(1):53–8.

    Article  PubMed  CAS  Google Scholar 

  34. Thompson IM, Ankerst DP, Chi C, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA. 2005;294(1):66–70.

    Article  PubMed  CAS  Google Scholar 

  35. Cooner WH, Mosley BR, Rutherford Jr CL, et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol. 1990;143(6): 1146–52.

    PubMed  CAS  Google Scholar 

  36. Catalona WJ, Smith DS, Ornstein DK. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA. 1997;277(18):1452–5.

    Article  PubMed  CAS  Google Scholar 

  37. Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2006;98(8): 529–34.

    Article  PubMed  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Bonilla RC, McConnel JD. Patterns of prostate growth observed in placebo treated patients in the PLESS trial over four years [abstract]. J Urol. 1995;159 Suppl 5:301A.

    Google Scholar 

  40. Oesterling JE, Jacobsen SJ, Chute CG, et al. Serum PSA in a community based population of healthy men: establishment of age reference ranges. JAMA. 1993;270:860–4.

    Article  PubMed  CAS  Google Scholar 

  41. Richardson TD, Oesterling JE. Age-specific reference ranges for serum prostate specific antigen. Urol Clin North Am. 1997;24:339–51.

    Article  PubMed  CAS  Google Scholar 

  42. Reed A, Ankerst DP, Pollock BH, et al. Current age and race adjusted prostate specific antigen threshold values delay diagnosis of high grade prostate cancer. J Urol. 2007;178:1929–32.

    Article  PubMed  Google Scholar 

  43. Stenman UH, Leinonen J, Alfthan H, et al. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991;51(1):222–6.

    PubMed  CAS  Google Scholar 

  44. Woodrum DL, Brawer MK, Partin AW, et al. Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. J Urol. 1998;159:5–12.

    Article  PubMed  CAS  Google Scholar 

  45. Catalona WJ, Partin AW, Slawin KM, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA. 1998;279(19):1542–7.

    Article  PubMed  CAS  Google Scholar 

  46. Benson MC, Whang IS, Olsson CA, et al. The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen. J Urol. 1992;147(3 Pt 2):817–21.

    PubMed  CAS  Google Scholar 

  47. Seaman E, Whang M, Olsson CA, et al. PSA density (PSAD). Role in patient evaluation and management. Urol Clin North Am. 1993;20(4):653–63.

    PubMed  CAS  Google Scholar 

  48. Catalona WJ, Richie JP, deKernion JB, et al. Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. J Urol. 1994;152(6 Pt 1):2031–6.

    PubMed  CAS  Google Scholar 

  49. Lepor H, Wang B, Shapiro E. Relationship between prostatic epithelial volume and serum prostate-specific antigen levels. Urology. 1994;44(2):199–205.

    Article  PubMed  CAS  Google Scholar 

  50. Kalish LJ, Cooner WH, Graham Jr SD. Serum PSA adjusted for volume of transition zone (PSAT) is more accurate than PSA adjusted for total gland volume (PSAD) in detecting adenocarcinoma of the prostate. Urology. 1994;43(5):601–6.

    Article  PubMed  CAS  Google Scholar 

  51. Djavan B, Zlotta AR, Byttebier G, et al. Prostate specific antigen density of the transition zone for early detection of prostate cancer. J Urol. 1998;160(2): 411–8.

    Article  PubMed  CAS  Google Scholar 

  52. Carter HB, Morrell CH, Pearson JD, et al. Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease. Cancer Res. 1992;52(12):3323–8.

    PubMed  CAS  Google Scholar 

  53. Loeb S, Roehl KA, Nadler RB, et al. Prostate specific antigen velocity in men with total prostate specific antigen less than 4 ng/ml. J Urol. 2007;178(6):2348–52.

    Article  PubMed  CAS  Google Scholar 

  54. D’Amico AV, Chen MH, Roehl KA, et al. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004;351(2):125–35.

    Article  PubMed  Google Scholar 

  55. Loeb S, Roehl KA, Catalona WJ, et al. Prostate specific antigen velocity threshold for predicting prostate cancer in young men. J Urol. 2007;177(3):899–902.

    Article  PubMed  Google Scholar 

  56. Moul JW, Sun L, Hotaling JM, et al. Age adjusted prostate specific antigen and prostate specific antigen velocity cut points in prostate cancer screening. J Urol. 2007;177(2):499–503.

    Article  PubMed  CAS  Google Scholar 

  57. Wolters T, Roobol MJ, Bangma CH, et al. Is prostate-specific antigen velocity selective for clinically significant prostate cancer in screening? European Randomized Study of Screening for Prostate Cancer (Rotterdam). Eur Urol. 2009;55(2):385–92.

    Article  PubMed  Google Scholar 

  58. Schmid H-P, McNeal JE, Stamey TA. Observations on the doubling time of prostate cancer. The use of serial prostate-specific antigen in patients with untreated disease as a measure of increasing cancer volume. Cancer. 1993;71(6):2031–40.

    Article  PubMed  CAS  Google Scholar 

  59. D’Amico AV, Hanks GE. Linear regressive analysis using prostate-specific antigen doubling time for predicting tumor biology and clinical outcome in prostate cancer. Cancer. 1993;72(9):2638–43.

    Article  PubMed  Google Scholar 

  60. Maffezzini M, Bossi A, Collette L. Implications of prostate-specific antigen doubling time as indicator of failure after surgery or radiation therapy for prostate cancer. Eur Urol. 2007;51(3):605–13.

    Article  PubMed  CAS  Google Scholar 

  61. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591–7.

    Article  PubMed  CAS  Google Scholar 

  62. D’Amico AV, Moul J, Carroll PR, et al. Prostate specific antigen doubling time as a surrogate end point for prostate cancer specific mortality following ­radical prostatectomy or radiation therapy. J Urol. 2004;172(5 Pt 2):S42–6.

    Article  PubMed  Google Scholar 

  63. 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.

    Article  PubMed  CAS  Google Scholar 

  64. Zelefsky MJ, Ben-Porat L, Scher HI, et al. Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer. J Clin Oncol. 2005;23(4):826–31.

    Article  PubMed  Google Scholar 

  65. Carducci MA, DeWeese TL, Nelson JB. Prostate-specific antigen and other markers of therapeutic response. Urol Clin North Am. 1999;26(2):291–302, viii.

    Google Scholar 

  66. Banu E, Banu A, Medioni J, et al. Serum PSA half-life as a predictor of survival for hormone-refractory prostate cancer patients: modelization using a standardized set of response criteria. Prostate. 2007;67(14):1543–9.

    Article  PubMed  Google Scholar 

  67. Andriole GL, Crawford ED, Grubb III RL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310–9.

    Article  PubMed  CAS  Google Scholar 

  68. Schröder 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.

    Article  PubMed  Google Scholar 

  69. Roobol MJ, Kerkhof M, Schröder FH, et al. Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol. 2009;56:584–91.

    Article  PubMed  Google Scholar 

  70. Ozen H, Aygun C, Ergen A, et al. Combined use of prostate-specific antigen derivatives decreases the number of unnecessary biopsies to detect prostate cancer.Am J Clin Oncol. 2001;24(6):610–3.

    Article  PubMed  Google Scholar 

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  1. Department of Urology, Haceteppe University School of Medicine, Ankara, 06100, Turkey

    Haluk Ozen & Sertac Yazici

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  1. Haluk Ozen
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  2. Sertac Yazici
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Correspondence to Haluk Ozen .

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  1. , Glickman Urological and Kidney, Cleveland Clinic, 9500 Euclid Ave, Cleveland, 44195, Ohio, USA

    Eric A. Klein

  2. Cleveland Clinic, Cleveland Clinic Lerner College of Medic, Department of Regional Urology, at Case Western Reserve, Cleveland, 44195, Ohio, USA

    J. Stephen Jones

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Ozen, H., Yazici, S. (2012). Twenty Years and Counting: Is PSA Still Useful in 2010?. In: Klein, E., Jones, J. (eds) Management of Prostate Cancer. Current Clinical Urology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-259-9_2

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  • DOI: https://doi.org/10.1007/978-1-60761-259-9_2

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