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prostate specific antigen (PSA) in serum

Pharmacokinetics: - PSA is found in serum complexed with alpha 1-antichymotrypsin (> 85%) & in free form. - another fraction is bound to alpha-2 macroglobulin, but is not available for detection by immunological methods - plasma clearance follows first order kinetics with a 1/2 life of 2-3 days Indications: - not recommended for routine screening for prostate cancer [22] - prostate cancer screening with serum PSA leads to overdetection & overtreatment of some patients [24] - a computer model suggests a higher PSA threshold for biopsy & longer screening intervals in men with low PSA levels would reduce the harms of screening [23] Benefit/risk: - no mortality benefit or prostate cancer-specific mortality benefit [26] - number needed to harm - 5 for 1 unnecessary prostate biopsy [26] Reference interval: - < 4 ug/L - risk of lethal prostate cancer very low in men with serum PSA of < 1 ug/L [28] - baseline serum PSA < 2 ng/mL at age 55-60 years associated with few cases of clinically significant prostate cancer later in life [29] Clinical significance: 1) serum levels (> 4 ug/L) are elevated in: a) benign prostatic hypertrophy b) prostatitis - levels at least as high 18-49 ng/mL may be observed - levels 2.5-10 ng/mL may be associated with asymptomatic prostatitis - antibiotic treatment of asymptomatic prostatitis may lower PSA but does not reduce risk of prostate cancer c) urinary retention, regardless of cause of obstruction [4] d) prostate cancer - serum levels > 10 ng/mL suggest prostate cancer [3] but are not diagnostic - serum level increases of > 2.0 ng/mL/year prior to surgery predicts prostate cancer recurrence after radical prostatectomy [9] - increases in PSA of > 0.35 ng/mL per year in early phase while PSA is within normal range may be associated with diminished survival [15] - refer for prostate biopsy [25] - neither digital rectal examination or PSA < 4 ug/L rules out prostate cancer e) any procedure that disturbs the prostate gland - indwelling urinary catheter - digital rectal exam, controversial - others, urologic etc. 2) serum levels correlate with weight of prostate [10] (mean PSA of 8 ng/mL) 3) levels flucuate such that a repeat level is indicated prior to an invasive procedure (i.e. prostate biopsy) 4) serum PSA < 1 ng/mL associated with low risk for clinically significant prostate cancer [27] Increases: 1) benign prostatic hypertrophy 2) prostatitis 3) urinary retention 4) prostate cancer Decreases: - finasteride & dutasteride can lower serum PSA as much as 50% (but does not diminish risk of prostate cancer) [25]* - low-dose dutasteride & finasteride reduce prostate specific antigen 25-31% [30] * to calculate a corrected serum PSA in patients on finasteride or dutasteride, multiply serum PSA x 2 [25] Management: Protocol: 1) annual PSA after age 50 (age 40 if African-American or family history of prostate cancer) 2) if PSA is > 4 ug/L (> 6 ug/L if > 65 years of age), order free PSA* - free PSA plays no role in active surveillance, prostate biopsy as indicated by protcol 3) if %free PSA is < 25%, then refer patient to urology for prostate biopsy 4) if patient is > 75 years, it is not necessary to order free PSA 5) if patient is > 75 years & PSA is > 20 ug/L, refer to urology/oncology for androgen deprivation therapy * With total PSA 4-10 ng/mL, 95% of men with prostate cancer have free PSA < 25%, 20% of men with BPH have free PSA < 25% Procedure: 1) serum levels depend on assay (15% variation Beckman vs Bayer) [8] 2) free PSA - two different antibodies used - one detects PSA complexed to alpha-1 antichymotrypsin; the other detects only free PSA - equilibrium dialysis is not useful since PSA is not easily dialyzed from PSA-apha-1 antichymotrypsin complex Notes: - test licensed by FDA in late 1980s [17]

Related

benign prostatic hyperplasia (BPH) prostate biopsy prostate cancer prostate-specific antigen (PSA) velocity prostate-specific antigen; PSA; gamma-seminoprotein; seminin; kallikrein-3; P-30 antigen; semenogelase (KLK3 APS) screening for prostate cancer

Specific

free prostate-specific antigen (free PSA) in serum/plasma

General

prostate specific antigen (PSA) in body fluid

References

  1. Clinical Diagnosis & Management by Laboratory Methods, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1991, pg 293
  2. Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 907
  3. Kaiser Permanente Northern California protocol, 1/2000
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Aronson WJ. in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  6. Journal Watch 23(14):113, 2003 Eastbam JA et al, Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations JAMA 289:2695,2003 PMID: 12771116
  7. Journal Watch 24(13):101, 2004
    1. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46. PMID: 15163773
    2. Carter HB, Isaacs WB. Improved biomarkers for prostate cancer: a definite need. J Natl Cancer Inst. 2004 Jun 2;96(11):813-5. No abstract available. PMID: 15173257
    3. Carter HB. Prostate cancers in men with low PSA levels--must we find them? N Engl J Med. 2004 May 27;350(22):2292-4. No abstract available. PMID: 15163780
  8. Journal Watch 24(14):111, 2004 Link RE, Shariat SF, Nguyen CV, Farr A, Weinberg AD, Morton RA, Richardson B, Bernard D, Slawin KM. Variation in prostate specific antigen results from 2 different assay platforms: clinical impact on 2304 patients undergoing prostate cancer screening. J Urol. 2004 Jun;171(6 Pt 1):2234-8. PMID: 15126793
  9. Journal Watch 24(15):120, 2004 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 Jul 8;351(2):125-35. PMID: 15247353
  10. Journal Watch 24(22):169, 2004 Stamey TA, Caldwell M, McNeal JE, Nolley R, Hemenez M, Downs J. The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol. 2004 Oct;172(4 Pt 1):1297-301. PMID: 15371827
  11. Welch HG, Schwartz LM, Woloshin S. Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst. 2005 Aug 3;97(15):1132-7. PMID: 160770711
  12. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, Richie JP, deKernion JB, Walsh PC, Scardino PT, Lange PH, Subong EN, Parson RE, Gasior GH, Loveland KG, Southwick PC. 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 May 20;279(19):1542-7. PMID: 9605898
  13. Scales CD et al Prostate-specific antigen testing in men older that 75 years in the United States. J Urolo 2006, 176:511 PMID: 16813879
  14. Walter LC et al, PSA screening among elderly men with limited life expectancies. JAMA 2006, 296:2336 PMID: 17105796
  15. Carter HB et al, Detection of life-threatening prostate cancer with prostate- specific antigen velocity during a window of curability. J Natl Cancer Inst 2006, 98:1521 PMID: 17077354
  16. Walter LC et al, PSA screening among elderly men with limited life expectancies. JAMA 2006, 296:2336 PMID: 17105796
  17. Wilkes, M UC Davis Medicine Grand Rounds, May 10, 2007
  18. Ankerst DP et al Yearly prostate specific antigen and digital rectal examination fluctuations in a screened population. J Urol 2009 May; 181:2071. PMID: 19286205 - Eastham JA et al Variation of serum prostate-specific antigen levels: An evaluation of year-to-year fluctuations. JAMA 2003 May 28; 289:2695-700. PMID: 12771116
  19. Stopiglia RM et al. Prostate specific antigen decrease and prostate cancer diagnosis: Antibiotic versus placebo prospective randomized clinical trial. J Urol 2010 Mar; 183:940 PMID: 20089269
  20. Prostate Specific Antigen, Total Laboratory Test Directory ARUP: 70121
  21. Panel of 3 tests Laboratory Test Directory ARUP: 80206
  22. Moyer VA et al Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement Annals of Internal Medicine, May 21, 2012 PMID: 22615453 http://www.annals.org/content/early/2012/05/21/0003-4819-157-2-201207170-00459.full (corresponding NGC guideline withdrawn Feb 2018)
  23. Gulati R et al Comparative Effectiveness of Alternative Prostate-Specific Antigen-Based Prostate Cancer Screening Strategies: Model Estimates of Potential Benefits and Harms Ann Intern Med. 5 February 2013;158(3):145-153 PMID: 23381039 http://annals.org/article.aspx?articleid=1567368 - Concato J Probability, Uncertainty, and Prostate Cancer Ann Intern Med. 5 February 2013;158(3):211-212 PMID: 23381041 http://annals.org/article.aspx?articleid=1567370
  24. Greene KL, Albertsen PC, Babaian RJ et al Prostate specific antigen best practice statement: 2009 update. J Urol. 2013 Jan;189(1 Suppl):S2-S11. PMID: 23234625
  25. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  26. The NNT: Prostate Specific Antigen (PSA) Test to Screen for Prostate Cancer. http://www.thennt.com/nnt/psa-test-to-screen-for-prostate-cancer/ - Djulbegovic M, Beyth RJ, Neuberger MM et al Screening for prostate cancer: systematic review and meta- analysis of randomised controlled trials. BMJ. 2010 Sep 14;341:c4543 PMID: 20843937
  27. Gelfond J et al. Intermediate-term risk of prostate cancer is directly related to baseline prostate specific antigen: Implications for reducing the burden of prostate specific antigen screening. J Urol 2015 Jul; 194:46. PMID: 25686543
  28. Brett AS Baseline PSA Level Predicts Subsequent Risk for Lethal Prostate Cancer. NEJM Journal Watch. Sept 1, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Preston MA, Batista JL, Wilson KM et al. Baseline prostate-specific antigen levels in midlife predict lethal prostate cancer. J Clin Oncol 2016 Aug 10; 34:2705 PMID: 27298404
  29. Kovac E, Carlsson sv, Lilja H et al. Association of baseline prostate-specific antigen level with long-term diagnosis of clinically significant prostate cancer among patients aged 55 to 60 years: A secondary analysis of a cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. JAMA Netw Open 2020 Jan 15; 3:e1919284 PMID: 31940039 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758743
  30. Kang HW, Chae MH, Park SH et al. Change in prostate specific antigen concentration in men with prostate specific antigen less than 2.5 ng/ml taking low dose finasteride or dutasteride for male androgenetic alopecia. J Urol. 2017;198(6):1340-1345 PMID: 28743526 https://www.auajournals.org/doi/10.1016/j.juro.2017.07.075
  31. Questions and Answers About the Prostate-Specific Antigen (PSA) Test http://cis.nci.nih.gov/fact/5_29.htm

Component-of

free prostate Specific antigen/prostate specific antigen total in serum/plasma