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Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects

  • Chapter
Book cover Advances in Cancer Biomarkers

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 867))

Abstract

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored.

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Abbreviations

% (−2)pPSA:

Percent (−2)proPSA (= (−2)pPSA/ fPSA)

%fPSA:

Percent free PSA (= fPSA/tPSA × 100 %)

(−2)pPSA:

(−2)proPSA (precursor form of prostate specific antigen)

(−4)pPSA:

(−4)proPSA (precursor form of prostate specific antigen)

(−5)pPSA:

(−5)proPSA (precursor form of prostate specific antigen)

(−7)pPSA:

(−7)proPSA (precursor form of prostate specific antigen)

Aa:

Amino-acids

ADC:

Apparent diffusion coefficient

AUA:

American Urological Association

BCR:

Biochemical recurrence

BPH:

Benign prostatic hyperplasia

BPSA:

Benign prostate specific antigen

cPSA:

Complexed prostate specific antigen

DCE:

Dynamic contrast-enhanced imaging

DD3:

Differential display clone 3 gene

DRE:

Digital rectal examination

DWI:

Diffusion weighted imaging

e.g.:

Exempli gratia (for example)

EAU:

European Association of Urology

ERSPC:

European randomized study of screening for prostate cancer

FDA:

United States Food and Drug Administration

fPSA:

Free prostate specific antigen

hK1:

Human kallikrein 1

hK2:

Human kallikrein 2

hK3:

Human kallikrein 3

hK4:

Human kallikrein 4

i.e.:

id est (that is)

iPSA:

Intact prostate specific antigen

LR:

Likelihood ratio

mpMRI :

Multiparametric MRI

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

MRSI:

Magnetic resonance spectroscopic imaging

PC:

Prostate cancer

PCA3 :

Prostate cancer antigen 3

PCPT:

Prostate cancer prevention trial

PFS:

Progression free survival rate

Phi:

Prostate health index ((−2)pPSA/fPSA) × √tPSA)

PLCO:

Prostate , lung, colorectal and ovarian screening trial

pPSA:

Pro prostate specific antigen

PPV:

Positive predictive value

PSA :

Prostate specific antigen

PSAD:

PSA- density

PSADT:

PSA-doubling time

PSAV:

PSA- velocity

RP:

Radical prostatectomy

RT:

Radiation therapy

T2WI:

T2- weighted images

TMPRRS2:

Transmembrane protease serine 2

tPSA:

Total prostate specific antigen

TRUS:

Transrectal ultrasound

References

  1. Villeirs GM, LV K, De Neve WJ, De Meerleer GO (2005) Magnetic resonance imaging anatomy of the prostate and periprostatic area: a guide for radiotherapists. Radiother Oncol 76(1):99–106

    Article  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  CAS  PubMed  Google Scholar 

  3. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6):1374–1403

    Article  CAS  PubMed  Google Scholar 

  4. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30

    Article  PubMed  Google Scholar 

  5. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O et al (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61(6):1079–1092

    Article  PubMed  Google Scholar 

  6. Gosselaar C, Kranse R, Roobol MJ, Roemeling S, Schroder FH (2008) The interobserver variability of digital rectal examination in a large randomized trial for the screening of prostate cancer. Prostate 68(9):985–993

    Article  CAS  PubMed  Google Scholar 

  7. Hodge KK, McNeal JE, Terris MK, Stamey TA (1989) Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 142(1):71–74, discussion 4–5

    CAS  PubMed  Google Scholar 

  8. Gleason DF (1966) Classification of prostatic carcinomas. Cancer Chemother Rep 50(3):125–128

    CAS  PubMed  Google Scholar 

  9. Mellinger GT, Gleason D, Bailar J 3rd (1967) The histology and prognosis of prostatic cancer. J Urol 97(2):331–337

    CAS  PubMed  Google Scholar 

  10. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL, Committee IG (2005) The 2005 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma. Am J Surg Pathol 29(9):1228–1242

    Article  PubMed  Google Scholar 

  11. Yousef GM, Luo LY, Diamandis EP (1999) Identification of novel human kallikrein-like genes on chromosome 19q13.3-q13.4. Anticancer Res 19(4B):2843–2852

    CAS  PubMed  Google Scholar 

  12. Hara M, Koyanagi Y, Inoue T, Fukuyama T (1971) Some physico-chemical characteristics of “ – seminoprotein”, an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. VII. Nihon Hoigaku Zasshi 25(4):322–324

    CAS  PubMed  Google Scholar 

  13. Wang MC, Valenzuela LA, Murphy GP, Chu TM (1979) Purification of a human prostate specific antigen. Invest Urol 17(2):159–163

    CAS  PubMed  Google Scholar 

  14. Li TS, Beling CG (1973) Isolation and characterization of two specific antigens of human seminal plasma. Fertil Steril 24(2):134–144

    CAS  PubMed  Google Scholar 

  15. Papsidero LD, Wang MC, Valenzuela LA, Murphy GP, Chu TM (1980) A prostate antigen in sera of prostatic cancer patients. Cancer Res 40(7):2428–2432

    CAS  PubMed  Google Scholar 

  16. Yousef GM, Diamandis EP (2001) The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 22(2):184–204

    CAS  PubMed  Google Scholar 

  17. Balk SP, Ko YJ, Bubley GJ (2003) Biology of prostate-specific antigen. J Clin Oncol 21(2):383–391

    Article  CAS  PubMed  Google Scholar 

  18. Lilja H (1985) A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 76(5):1899–1903

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lovgren J, Valtonen-Andre C, Marsal K, Lilja H, Lundwall A (1999) Measurement of prostate-specific antigen and human glandular kallikrein 2 in different body fluids. J Androl 20(3):348–355

    CAS  PubMed  Google Scholar 

  20. Stephan C, Jung K, Lein M, Diamandis EP (2007) PSA and other tissue kallikreins for prostate cancer detection. Eur J Cancer 43(13):1918–1926

    Article  CAS  PubMed  Google Scholar 

  21. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E (1987) Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 317(15):909–916

    Article  CAS  PubMed  Google Scholar 

  22. Oesterling JE, Chan DW, Epstein JI, Kimball AW Jr, Bruzek DJ, Rock RC et al (1988) Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy. J Urol 139(4):766–772

    CAS  PubMed  Google Scholar 

  23. Kumar A, Mikolajczyk SD, Goel AS, Millar LS, Saedi MS (1997) Expression of pro form of prostate-specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2. Cancer Res 57(15):3111–3114

    CAS  PubMed  Google Scholar 

  24. Mikolajczyk SD, Millar LS, Wang TJ, Rittenhouse HG, Wolfert RL, Marks LS et al (2000) “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 55(1):41–45

    Article  CAS  PubMed  Google Scholar 

  25. Mikolajczyk SD, Millar LS, Wang TJ, Rittenhouse HG, Marks LS, Song W et al (2000) A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. Cancer Res 60(3):756–759

    CAS  PubMed  Google Scholar 

  26. Mikolajczyk SD, Grauer LS, Millar LS, Hill TM, Kumar A, Rittenhouse HG et al (1997) A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 50(5):710–714

    Article  CAS  PubMed  Google Scholar 

  27. Link RE, Shariat SF, Nguyen CV, Farr A, Weinberg AD, Morton RA et al (2004) Variation in prostate specific antigen results from 2 different assay platforms: clinical impact on 2304 patients undergoing prostate cancer screening. J Urol 171(6 Pt 1):2234–2238

    Article  CAS  PubMed  Google Scholar 

  28. Loeb S, Catalona WJ (2008) What to do with an abnormal PSA test. Oncologist 13(3):299–305

    Article  CAS  PubMed  Google Scholar 

  29. Blijenberg BG, Yurdakul G, Van Zelst BD, Bangma CH, Wildhagen MF, Schroder FH (2001) Discordant performance of assays for free and total prostate-specific antigen in relation to the early detection of prostate cancer. BJU Int 88(6):545–550

    Article  CAS  PubMed  Google Scholar 

  30. Rafferty B, Rigsby P, Rose M, Stamey T, Gaines DR (2000) Reference reagents for prostate-specific antigen (PSA): establishment of the first international standards for free PSA and PSA (90:10). Clin Chem 46(9):1310–1317

    CAS  PubMed  Google Scholar 

  31. Bangma CH, van Schaik RH, Blijenberg BG, Roobol MJ, Lilja H, Stenman UH (2010) On the use of prostate-specific antigen for screening of prostate cancer in European randomised study for screening of prostate cancer. Eur J Cancer 46(17):3109–3119

    Article  PubMed  Google Scholar 

  32. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL et al (2004) Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med 350(22):2239–2246

    Article  CAS  PubMed  Google Scholar 

  33. Oesterling JE (1991) Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol 145(5):907–923

    CAS  PubMed  Google Scholar 

  34. Nadler RB, Humphrey PA, Smith DS, Catalona WJ, Ratliff TL (1995) Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol 154(2 Pt 1):407–413

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. Schroder FH, Carter HB, Wolters T, van den Bergh RC, Gosselaar C, Bangma CH et al (2008) Early detection of prostate cancer in 2007. Part 1: PSA and PSA kinetics. Eur Urol 53(3):468–477

    Article  PubMed  Google Scholar 

  37. Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis RA, Schroder FH et al (2003) Lead times and overdetection due to prostate-specific antigen screening: estimates from the European randomized study of screening for prostate cancer. J Natl Cancer Inst 95(12):868–878

    Article  PubMed  Google Scholar 

  38. Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O (1991) 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 51(1):222–226

    CAS  PubMed  Google Scholar 

  39. Lilja H, Christensson A, Dahlen U, Matikainen MT, Nilsson O, Pettersson K et al (1991) Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. Clin Chem 37(9):1618–1625

    CAS  PubMed  Google Scholar 

  40. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A et al (1998) 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 279(19):1542–1547

    Article  CAS  PubMed  Google Scholar 

  41. Roddam AW, Duffy MJ, Hamdy FC, Ward AM, Patnick J, Price CP et al (2005) Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2–10 ng/ml: systematic review and meta-analysis. Eur Urol 48(3):386–399, discussion 98–9

    Article  CAS  PubMed  Google Scholar 

  42. Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS, Free PSASG (2006) A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 67(4):762–768

    Article  PubMed  Google Scholar 

  43. Catalona WJ, Southwick PC, Slawin KM, Partin AW, Brawer MK, Flanigan RC et al (2000) Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging. Urology 56(2):255–260

    Article  CAS  PubMed  Google Scholar 

  44. Finne P, Auvinen A, Maattanen L, Tammela TL, Ruutu M, Juusela H et al (2008) Diagnostic value of free prostate-specific antigen among men with a prostate-specific antigen level of <3.0 microg per liter. Eur Urol 54(2):362–370

    Article  CAS  PubMed  Google Scholar 

  45. Catalona WJ, Bartsch G, Rittenhouse HG, Evans CL, Linton HJ, Horninger W et al (2004) Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen. J Urol 171(6 Pt 1):2239–2244

    Article  PubMed  Google Scholar 

  46. Mikolajczyk SD, Catalona WJ, Evans CL, Linton HJ, Millar LS, Marker KM et al (2004) Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Chem 50(6):1017–1025

    Article  CAS  PubMed  Google Scholar 

  47. de Vries SH, Raaijmakers R, Blijenberg BG, Mikolajczyk SD, Rittenhouse HG, Schroder FH (2005) Additional use of [−2] precursor prostate-specific antigen and “benign” PSA at diagnosis in screen-detected prostate cancer. Urology 65(5):926–930

    Article  PubMed  Google Scholar 

  48. Bangma CH, Wildhagen MF, Yurdakul G, Schroder FH, Blijenberg BG (2004) The value of (−7, −5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer. BJU Int 93(6):720–724

    Article  CAS  PubMed  Google Scholar 

  49. Hori S, Blanchet JS, McLoughlin J (2013) From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSAs in the detection and management of early prostate cancer. BJU Int 112(6):717–728

    Google Scholar 

  50. Lein M, Semjonow A, Graefen M, Kwiatkowski M, Abramjuk C, Stephan C et al (2005) A multicenter clinical trial on the use of (−5, −7) pro prostate specific antigen. J Urol 174(6):2150–2153

    Article  CAS  PubMed  Google Scholar 

  51. Miyakubo M, Ito K, Yamamoto T, Takechi H, Ohi M, Suzuki K (2009) Proprostate-specific antigen: its usefulness in the era of multiple-core prostate biopsy. Int J Urol 16(6):561–565

    Article  CAS  PubMed  Google Scholar 

  52. Sokoll LJ, Sanda MG, Feng Z, Kagan J, Mizrahi IA, Broyles DL et al (2010) A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [−2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 19(5):1193–1200

    Article  PubMed Central  PubMed  Google Scholar 

  53. Rhodes T, Jacobson DJ, McGree ME, St Sauver JL, Girman CJ, Lieber MM et al (2012) Longitudinal changes of benign prostate-specific antigen and [−2]proprostate-specific antigen in seven years in a community-based sample of men. Urology 79(3):655–661

    Article  PubMed Central  PubMed  Google Scholar 

  54. Jansen FH, van Schaik RH, Kurstjens J, Horninger W, Klocker H, Bektic J et al (2010) Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection. Eur Urol 57(6):921–927

    Article  CAS  PubMed  Google Scholar 

  55. Lazzeri M, Haese A, de la Taille A, Palou Redorta J, McNicholas T, Lughezzani G et al (2013) 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 Urol 63(6):986–994

    Article  CAS  PubMed  Google Scholar 

  56. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A (2013) Multicenter evaluation of [−2]proprostate-specific antigen and the prostate health index for detecting prostate cancer. Clin Chem 59(1):306–314

    Article  CAS  PubMed  Google Scholar 

  57. Benson MC, Whang IS, Pantuck A, Ring K, Kaplan SA, Olsson CA et al (1992) Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 147(3 Pt 2):815–816

    CAS  PubMed  Google Scholar 

  58. Benson MC, McMahon DJ, Cooner WH, Olsson CA (1993) An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density. World J Urol 11(4):206–213

    Article  CAS  PubMed  Google Scholar 

  59. Loeb S, Han M, Roehl KA, Antenor JA, Catalona WJ (2005) Accuracy of prostate weight estimation by digital rectal examination versus transrectal ultrasonography. J Urol 173(1):63–65

    Article  PubMed  Google Scholar 

  60. Connolly D, Black A, Murray LJ, Napolitano G, Gavin A, Keane PF (2007) Methods of calculating prostate-specific antigen velocity. Eur Urol 52(4):1044–1050

    Article  PubMed  CAS  Google Scholar 

  61. Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R et al (1992) Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 267(16):2215–2220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Carter HB, Ferrucci L, Kettermann A, Landis P, Wright EJ, Epstein JI et al (2006) Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. J Natl Cancer Inst 98(21):1521–1527

    Article  PubMed Central  PubMed  Google Scholar 

  63. Vickers AJ, Wolters T, Savage CJ, Cronin AM, O’Brien MF, Pettersson K et al (2009) Prostate-specific antigen velocity for early detection of prostate cancer: result from a large, representative, population-based cohort. Eur Urol 56(5):753–760

    Article  PubMed Central  PubMed  Google Scholar 

  64. Wolters T, Roobol MJ, Bangma CH, Schroder FH (2009) Is prostate-specific antigen velocity selective for clinically significant prostate cancer in screening? European randomized study of screening for prostate cancer (Rotterdam). Eur Urol 55(2):385–392

    Article  PubMed  Google Scholar 

  65. Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS et al (2006) Assessing prostate cancer risk: results from the prostate cancer prevention trial. J Natl Cancer Inst 98(8):529–534

    Article  PubMed  Google Scholar 

  66. Orsted DD, Bojesen SE, Kamstrup PR, Nordestgaard BG (2013) Long-term prostate-specific antigen velocity in improved classification of prostate cancer risk and mortality. Eur Urol 64(3):384–393

    Google Scholar 

  67. Vickers AJ, Savage C, O’Brien MF, Lilja H (2009) Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol 27(3):398–403

    Article  PubMed Central  PubMed  Google Scholar 

  68. Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM (2011) An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. J Natl Cancer Inst 103(6):462–469

    Article  PubMed Central  PubMed  Google Scholar 

  69. D’Amico AV, Chen MH, Roehl KA, Catalona WJ (2004) Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 351(2):125–135

    Article  PubMed  Google Scholar 

  70. D’Amico AV, Renshaw AA, Sussman B, Chen MH (2005) Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy. JAMA 294(4):440–447

    Article  PubMed  Google Scholar 

  71. Guideline Pc. Available from: http://www.uroweb.org/guidelines/online-guidelines/

  72. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC (1999) Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281(17):1591–1597

    Article  CAS  PubMed  Google Scholar 

  73. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC et al (2005) Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 294(4):433–439

    Article  CAS  PubMed  Google Scholar 

  74. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC et al (2007) Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality. J Clin Oncol 25(13):1765–1771

    Article  PubMed  Google Scholar 

  75. Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A et al (2013) Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol 63(4):597–603

    Article  PubMed  Google Scholar 

  76. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA et al (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59(23):5975–5979

    CAS  PubMed  Google Scholar 

  77. Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B et al (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44(1):8–15, discussion −6

    Article  CAS  PubMed  Google Scholar 

  78. Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C et al (2006) APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 52(6):1089–1095

    Article  CAS  PubMed  Google Scholar 

  79. Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW et al (2008) PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 179(4):1587–1592

    Article  PubMed  Google Scholar 

  80. Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM et al (2007) PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 69(3):532–535

    Article  PubMed  Google Scholar 

  81. Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF et al (2008) Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 54(5):1081–1088

    Article  PubMed  Google Scholar 

  82. Auprich M, Haese A, Walz J, Pummer K, de la Taille A, Graefen M et al (2010) External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome. Eur Urol 58(5):727–732

    Article  PubMed  Google Scholar 

  83. Roobol MJ, Schroder FH, van Leeuwen P, Wolters T, van den Bergh RC, van Leenders GJ et al (2010) Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test. Eur Urol 58(4):475–481

    Article  CAS  PubMed  Google Scholar 

  84. Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N (2013) Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. J Urol 190(2):389–398

    Article  CAS  PubMed  Google Scholar 

  85. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW et al (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310(5748):644–648

    Article  CAS  PubMed  Google Scholar 

  86. Laxman B, Tomlins SA, Mehra R, Morris DS, Wang L, Helgeson BE et al (2006) Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 8(10):885–888

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Laxman B, Morris DS, Yu J, Siddiqui J, Cao J, Mehra R et al (2008) A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res 68(3):645–649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Hessels D, Smit FP, Verhaegh GW, Witjes JA, Cornel EB, Schalken JA (2007) Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res 13(17):5103–5108

    Article  CAS  PubMed  Google Scholar 

  89. Tomlins SA, Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S et al (2011) Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med 3(94):94ra72

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Kuriyama M, Wang MC, Papsidero LD, Killian CS, Shimano T, Valenzuela L et al (1980) Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay. Cancer Res 40(12):4658–4662

    CAS  PubMed  Google Scholar 

  91. Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR et al (2007) Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 177(2):540–545

    Article  CAS  PubMed  Google Scholar 

  92. Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH et al (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference. Int J Radiat Oncol Biol Phys 65(4):965–974

    Article  PubMed  Google Scholar 

  93. Antenor JA, Roehl KA, Eggener SE, Kundu SD, Han M, Catalona WJ (2005) Preoperative PSA and progression-free survival after radical prostatectomy for stage T1c disease. Urology 66(1):156–160

    Article  PubMed  Google Scholar 

  94. Vickers AJ, Cronin AM, Bjork T, Manjer J, Nilsson PM, Dahlin A et al (2010) Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study. BMJ 341:c4521

    Article  PubMed Central  PubMed  Google Scholar 

  95. Loeb S, Carter HB, Catalona WJ, Moul JW, Schroder FH (2012) Baseline prostate-specific antigen testing at a young age. Eur Urol 61(1):1–7

    Article  PubMed  Google Scholar 

  96. Zhu X, Albertsen PC, Andriole GL, Roobol MJ, Schroder FH, Vickers AJ (2012) Risk-based prostate cancer screening. Eur Urol 61(4):652–661

    Article  PubMed  Google Scholar 

  97. Lilja H, Cronin AM, Dahlin A, Manjer J, Nilsson PM, Eastham JA et al (2011) Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50. Cancer 117(6):1210–1219

    Article  PubMed Central  PubMed  Google Scholar 

  98. Vickers AJ, Ulmert D, Sjoberg DD, Bennette CJ, Bjork T, Gerdtsson A et al (2013) Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40–55 and long term risk of metastasis: case-control study. BMJ 346:f2023

    Article  PubMed Central  PubMed  Google Scholar 

  99. Available from: http://www.prostaatwijzer.nl/medical-risk-calculators

  100. Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC et al (1994) Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 151(5):1283–1290

    CAS  PubMed  Google Scholar 

  101. Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ et al (1991) Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324(17):1156–1161

    Article  CAS  PubMed  Google Scholar 

  102. Catalona WJ, Smith DS, Ratliff TL, Basler JW (1993) Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. JAMA 270(8):948–954

    Article  CAS  PubMed  Google Scholar 

  103. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR et al (2012) Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 104(2):125–132

    Article  PubMed Central  PubMed  Google Scholar 

  104. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V et al (2012) Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 366(11):981–990

    Article  PubMed  Google Scholar 

  105. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P et al (2010) Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 11(8):725–732

    Article  PubMed Central  PubMed  Google Scholar 

  106. Labrie F, Candas B, Cusan L, Gomez JL, Belanger A, Brousseau G et al (2004) Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospective randomized controlled trial. Prostate 59(3):311–318

    Article  PubMed  Google Scholar 

  107. Kjellman A, Akre O, Norming U, Tornblom M, Gustafsson O (2009) 15-year followup of a population based prostate cancer screening study. J Urol 181(4):1615–1621, discussion 21

    Article  PubMed  Google Scholar 

  108. Sandblom G, Varenhorst E, Rosell J, Lofman O, Carlsson P (2011) Randomised prostate cancer screening trial: 20 year follow-up. BMJ 342:d1539

    Article  PubMed Central  PubMed  Google Scholar 

  109. Jemal A, Ward E, Wu X, Martin HJ, McLaughlin CC, Thun MJ (2005) Geographic patterns of prostate cancer mortality and variations in access to medical care in the United States. Cancer Epidemiol Biomarkers Prev 14(3):590–595

    Article  PubMed  Google Scholar 

  110. Moyer VA, Force USPST (2012) Screening for prostate cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med 157(2):120–134

    Article  PubMed  Google Scholar 

  111. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R et al (2011) Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 155(11):762–771

    Article  PubMed  Google Scholar 

  112. Carlsson S, Vickers AJ, Roobol M, Eastham J, Scardino P, Lilja H et al (2012) Prostate cancer screening: facts, statistics, and interpretation in response to the US Preventive Services Task Force review. J Clin Oncol 30(21):2581–2584

    Article  PubMed Central  PubMed  Google Scholar 

  113. Ilic D, Neuberger MM, Djulbegovic M, Dahm P (2013) Screening for prostate cancer. Cochrane Database Syst Rev 1:CD004720

    PubMed  Google Scholar 

  114. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B et al (2010) Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ 341:c4543

    Article  PubMed Central  PubMed  Google Scholar 

  115. Roobol MJ, Carlsson S, Hugosson J (2011) Meta-analysis finds screening for prostate cancer with PSA does not reduce prostate cancer-related or all-cause mortality but results likely due to heterogeneity – the two highest quality studies identified do find prostate cancer-related mortality reductions. Evid Based Med 16(1):20–21

    Article  PubMed  Google Scholar 

  116. Schroder F, Kattan MW (2008) The comparability of models for predicting the risk of a positive prostate biopsy with prostate-specific antigen alone: a systematic review. Eur Urol 54(2):274–290

    Article  PubMed  Google Scholar 

  117. van den Bergh RC, Roobol MJ, Wolters T, van Leeuwen PJ, Schroder FH (2008) The prostate cancer prevention trial and European randomized study of screening for prostate cancer risk calculators indicating a positive prostate biopsy: a comparison. BJU Int 102(9):1068–1073

    Article  PubMed  Google Scholar 

  118. Cavadas V, Osorio L, Sabell F, Teves F, Branco F, Silva-Ramos M (2010) Prostate cancer prevention trial and European randomized study of screening for prostate cancer risk calculators: a performance comparison in a contemporary screened cohort. Eur Urol 58(4):551–558

    Article  PubMed  Google Scholar 

  119. Oliveira M, Marques V, Carvalho AP, Santos A (2011) Head-to-head comparison of two online nomograms for prostate biopsy outcome prediction. BJU Int 107(11):1780–1783

    Article  PubMed  Google Scholar 

  120. Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G et al (2012) ESUR prostate MR guidelines 2012. Eur Radiol [Practice Guideline] 22(4):746–757

    Article  Google Scholar 

  121. Park BK, Lee HM, Kim CK, Choi HY, Park JW (2008) Lesion localization in patients with a previous negative transrectal ultrasound biopsy and persistently elevated prostate specific antigen level using diffusion-weighted imaging at three Tesla before rebiopsy. Invest Radiol [Clinical Trial] 43(11):789–793

    Article  Google Scholar 

  122. Sciarra A, Panebianco V, Ciccariello M, Salciccia S, Cattarino S, Lisi D et al (2010) Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res [Clinical Trial Randomized Controlled Trial] 16(6):1875–1883

    CAS  Google Scholar 

  123. Iwazawa J, Mitani T, Sassa S, Ohue S (2011) Prostate cancer detection with MRI: is dynamic contrast-enhanced imaging necessary in addition to diffusion-weighted imaging? Diagn Interv Radiol [Comparative Study] 17(3):243–248

    Google Scholar 

  124. Tamada T, Sone T, Higashi H, Jo Y, Yamamoto A, Kanki A et al (2011) Prostate cancer detection in patients with total serum prostate-specific antigen levels of 4–10 ng/mL: diagnostic efficacy of diffusion-weighted imaging, dynamic contrast-enhanced MRI, and T2-weighted imaging. AJR Am J Roentgenol [Research Support, Non-US Gov’t] 197(3):664–670

    Article  Google Scholar 

  125. Kitajima K, Kaji Y, Fukabori Y, Yoshida K, Suganuma N, Sugimura K (2010) Prostate cancer detection with 3 T MRI: comparison of diffusion-weighted imaging and dynamic contrast-enhanced MRI in combination with T2-weighted imaging. J Magn Reson Imaging 31(3):625–631

    Article  PubMed  Google Scholar 

  126. Tanimoto A, Nakashima J, Kohno H, Shinmoto H, Kuribayashi S (2007) Prostate cancer screening: the clinical value of diffusion-weighted imaging and dynamic MR imaging in combination with T2-weighted imaging. J Magn Reson Imaging 25(1):146–152

    Article  PubMed  Google Scholar 

  127. Dickinson L, Ahmed HU, Allen C, Barentsz JO, Carey B, Futterer JJ et al (2013) Scoring systems used for the interpretation and reporting of multiparametric MRI for prostate cancer detection, localization, and characterization: could standardization lead to improved utilization of imaging within the diagnostic pathway? J Magn Reson Imaging 37(1):48–58

    Article  PubMed  Google Scholar 

  128. Moore CM, Kasivisvanathan V, Eggener S, Emberton M, Futterer JJ, Gill IS et al (2013) Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an international working group. Eur Urol 64(4):544–552

    Article  PubMed  Google Scholar 

  129. Moore CM, Robertson NL, Arsanious N, Middleton T, Villers A, Klotz L et al (2013) Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol 63(1):125–140

    Article  PubMed  Google Scholar 

  130. Kattan MW, Eastham JA, Wheeler TM, Maru N, Scardino PT, Erbersdobler A et al (2003) Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors. J Urol 170(5):1792–1797

    Article  PubMed  Google Scholar 

  131. Roemeling S, Roobol MJ, Kattan MW, van der Kwast TH, Steyerberg EW, Schroder FH (2007) Nomogram use for the prediction of indolent prostate cancer: impact on screen-detected populations. Cancer [Randomized Controlled Trial Research Support, Non-US Gov’t] 110(10):2218–2221

    Google Scholar 

  132. Shukla-Dave A, Hricak H, Akin O, Yu C, Zakian KL, Udo K et al (2012) Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer. BJU Int [Research Support, NIH, Extramural Validation Studies] 109(9):1315–1322

    Google Scholar 

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  1. Department of Urology, Erasmus Medical Centre, Na-1710, 2040, 3000 CA, Rotterdam, Netherlands

    J. W. Salman, I. G. Schoots, S. V. Carlsson, G. Jenster & M. J. Roobol

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  2. I. G. Schoots
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    Roberto Scatena

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Salman, J.W., Schoots, I.G., Carlsson, S.V., Jenster, G., Roobol, M.J. (2015). Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects. In: Scatena, R. (eds) Advances in Cancer Biomarkers. Advances in Experimental Medicine and Biology, vol 867. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7215-0_7

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