A Review on the Clinical Utility of PSA in Cancer Prostate

Prostate cancer has come to share the oncological centrestage among male cancers. The availability of Serum Prostate Specific Antigen, PSA, as a marker has encouraged it’s use to diagnose both cancer and cancer recurrence. Some clarity is required about its precise role in clinical practice. The available literature on Prostate Specific Antigen was reviewed; Articles were reviewed for content, applicability to the problem at hand, availability of data about sensitivity and specificity of values, refinements in measurements and finally for impact of screening programmes using these values on survival and quality of life. The data in the literature was critically re-evaluated and analysed to draw reasonable conclusions. Serum PSA measurements show variable reliability when it comes to diagnosis of Prostate cancer, given the dynamics of PSA physiology. Surrogate measures like PSA density, PSA velocity, free-to-complexed PSA ratio, percentage Pro-PSA, etc., have been used to improve the predictive utility of this assay for Prostate cancer. The ability of PSA to detect those cancers that will cost life, and thereby permit early curative treatment, is as yet unclear. It’s most definitive role appears to be in diagnosing recurrences after adequate surgical treatment, and in evaluating response to treatment.

[1]  L. Ferrucci,et al.  Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. , 2006, Journal of the National Cancer Institute.

[2]  Sudhir Srivastava,et al.  A Prospective, Multicenter, National Cancer Institute Early Detection Research Network Study of [−2]proPSA: Improving Prostate Cancer Detection and Correlating with Cancer Aggressiveness , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[3]  E. Metter,et al.  Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis. , 1997, Urology.

[4]  Alan W Partin,et al.  Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. , 2005, JAMA.

[5]  D. Kuban,et al.  PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis. , 2004, International journal of radiation oncology, biology, physics.

[6]  G. Perry,et al.  Serum prostate-specific antigen profile following radiotherapy for prostate cancer: implications for patterns of failure and definition of cure. , 1998, Urology.

[7]  Peter H Gann,et al.  Prostate specific antigen best practice statement: 2009 update. , 2009, The Journal of urology.

[8]  James D. Cox,et al.  Consensus statement: Guidelines for PSA following radiation therapy , 1997 .

[9]  Ian M Thompson,et al.  Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. , 2005, JAMA.

[10]  T. Wilt,et al.  Systematic Review: Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer , 2008, Annals of Internal Medicine.

[11]  T. Stamey,et al.  Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. , 1988, The New England journal of medicine.

[12]  A. Pantuck,et al.  Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. , 1992, The Journal of urology.

[13]  D. Budman,et al.  Down-regulation of prostate-specific antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binding consensus in the promoter of the PSA gene in LNCaP cells. , 1997, Cancer research.

[14]  A. D'Amico,et al.  Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. , 2007, The Lancet. Oncology.

[15]  D. Chan,et al.  Multicenter Evaluation of the Performance and Clinical Utility in Longitudinal Monitoring of the Bayer Immuno 1™ Complexed PSA Assay , 1999, The International journal of biological markers.

[16]  Alan W Partin,et al.  Prostate-specific antigen as a marker of disease activity in prostate cancer. , 2002, Oncology.

[17]  J. Oesterling,et al.  Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer. , 1996, Urology.

[18]  M. Benson,et al.  The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen. , 1992, The Journal of urology.

[19]  D Robert Siemens,et al.  Prostatitis and prostate cancer: implications for prostate cancer screening. , 2004, Urology.

[20]  B. Littenberg,et al.  Using the free-to-total prostate-specific antigen ratio to detect prostate cancer in men with nonspecific elevations of prostate-specific antigen levels , 2000, Journal of General Internal Medicine.

[21]  A. Localio,et al.  A meta-analysis of the performance characteristics of the free prostate-specific antigen test. , 2006, Urology.

[22]  Lisa M. Schwartz,et al.  Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. , 2005, Journal of the National Cancer Institute.

[23]  D. Tindall,et al.  The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. , 2011, The Journal of urology.

[24]  O. Nilsson,et al.  Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. , 1993, The Journal of urology.

[25]  A. Renshaw,et al.  Adult urologyUrological survey: urological oncology: prostate cancerPretreatment PSA Velocity and Risk of Death From Prostate Cancer Following External Beam Radiation Therapy , 2006 .

[26]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[27]  E. Feuer,et al.  SEER Cancer Statistics Review, 1975-2003, National Cancer Institute. Bethesda, MD, , 2006 .

[28]  C. Ed Prostate Cancer Awareness Week: September 22 to 28, 1997. , 1997 .

[29]  J. Oesterling,et al.  Ejaculation increases the serum prostate-specific antigen concentration. , 1996, Urology.

[30]  W. J. Allard,et al.  Novel immunoassay for the measurement of complexed prostate-specific antigen in serum. , 1998, Clinical chemistry.

[31]  A. Hanlon,et al.  Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[32]  D. McCullough,et al.  Correlation of prostate-specific antigen and prostate-specific antigen density with outcome of prostate biopsy. , 1994, Urology.

[33]  E. Metter,et al.  Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. , 1992, JAMA.

[34]  A. D'Amico,et al.  American Cancer Society Guideline for the Early Detection of Prostate Cancer: Update 2010 , 2010, CA: a cancer journal for clinicians.

[35]  Ruth Etzioni,et al.  Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial. , 2005, The Journal of urology.

[36]  H. D. de Koning,et al.  Prostate cancer detection at low prostate specific antigen. , 2000, The Journal of urology.

[37]  A. Partin,et al.  Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. , 1994, Urology.

[38]  I. Thompson,et al.  The association of body mass index and prostate‐specific antigen in a population‐based study , 2005, Cancer.

[39]  P. Walsh,et al.  Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. , 2005, The Journal of urology.

[40]  R. Bruskewitz,et al.  Analysis of variation in prostate-specific antigen values. , 1993, Urology.

[41]  B. G. Blijenberg,et al.  Screening and prostate-cancer mortality in a randomized European study. , 2009, The New England journal of medicine.

[42]  Michael J Barry,et al.  Health Decision Aids To Facilitate Shared Decision Making in Office Practice , 2002, Annals of Internal Medicine.

[43]  D. Hussey American Society for Therapeutic Radiology and Oncology , 2001 .

[44]  R. Lamerz,et al.  Screening for prostatic carcinoma with prostate specific antigen. , 1997, Anticancer research.

[45]  A. Neugut,et al.  Obesity and screening PSA levels among men undergoing an annual physical exam , 2008, The Prostate.

[46]  W. Catalona,et al.  Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels. , 1992, The Journal of urology.

[47]  A. Lu,et al.  Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml. , 2002, The Journal of urology.

[48]  D. Ornstein,et al.  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. , 1997, JAMA.

[49]  D. Kuban,et al.  Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. , 1999, JAMA.

[50]  H Ballentine Carter,et al.  Prostate cancers in men with low PSA levels--must we find them? , 2004, The New England journal of medicine.

[51]  A. D'Amico,et al.  Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  O. Nilsson,et al.  Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. , 1991, Clinical chemistry.

[53]  J. Oesterling,et al.  Interpreting results of prostate-specific antigen testing for early detection of prostate cancer , 1996, Journal of General Internal Medicine.

[54]  Steven L. Chang,et al.  Impact of common medications on serum total prostate-specific antigen levels: analysis of the National Health and Nutrition Examination Survey. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  U. P. S. T. Force,et al.  Screening for Prostate Cancer: Recommendation and Rationale , 2002, Annals of Internal Medicine.

[56]  Jill,et al.  Effect of digital rectal examination on serum prostate-specific antigen in a primary care setting. The Internal Medicine Clinic Research Consortium. , 1995, Archives of internal medicine.

[57]  A W Partin,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. , 1998, JAMA.

[58]  C. Reddy,et al.  Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era. , 2002, International journal of radiation oncology, biology, physics.

[59]  M. Desai,et al.  Age-specific prostate specific antigen and prostate specific antigen density values in a community-based Indian population , 2007, Indian journal of urology : IJU : journal of the Urological Society of India.

[60]  Long-term durability of PSA failure-free survival after radiotherapy for localized prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[61]  E. Crawford Prostate Cancer Awareness Week: September 22 to 28, 1997 , 1997, CA: a cancer journal for clinicians.

[62]  J. Stanford,et al.  The Distribution of Serum Prostate‐Specific Antigen Levels Among American Men: Implications for Prostate Cancer Prevalence and Screening , 2006, The Prostate.

[63]  C Coley,et al.  Prostate-specific antigen best practice policy--part I: early detection and diagnosis of prostate cancer. , 2001, Urology.

[64]  J. Michalski,et al.  Chemical disease-free survival in localized carcinoma of prostate treated with external beam irradiation: comparison of American Society of Therapeutic Radiology and Oncology Consensus or 1 ng/mL as endpoint. , 2001, International journal of radiation oncology, biology, physics.

[65]  C G Chute,et al.  Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. , 1993, JAMA.

[66]  A W Partin,et al.  Natural history of progression after PSA elevation following radical prostatectomy. , 1999, JAMA.

[67]  J. Hugosson,et al.  Assessment of intra‐individual variation in prostate‐specific antigen levels in a biennial randomized prostate cancer screening program in Sweden , 2005, The Prostate.

[68]  S. Kanazawa,et al.  Prostate‐specific antigen ‘bounce’ after permanent 125I‐implant brachytherapy in Japanese men: a multi‐institutional pooled analysis , 2009, BJU international.

[69]  S. Gilbert,et al.  Evidence suggesting PSA cutpoint of 2.5 ng/mL for prompting prostate biopsy: review of 36,316 biopsies. , 2005, Urology.

[70]  E. Platz,et al.  Statin drugs, serum cholesterol, and prostate-specific antigen in the National Health and Nutrition Examination Survey 2001–2004 , 2010, Cancer Causes & Control.

[71]  Paul Schellhammer,et al.  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. , 2006, International journal of radiation oncology, biology, physics.

[72]  J. Oesterling,et al.  The effect of prostatitis, urinary retention, ejaculation, and ambulation on the serum prostate-specific antigen concentration. , 1997, The Urologic clinics of North America.

[73]  H. Morgenstern,et al.  Body composition and serum prostate-specific antigen: review and findings from Flint Men's Health Study. , 2008, Urology.

[74]  W. Catalona,et al.  Effect of ejaculation on serum total and free prostate-specific antigen concentrations. , 1997, Urology.

[75]  H. Uno,et al.  Clinical Evaluation of Serum Prostate‐Specific Antigen‐Alpha1 ‐ Antichymotrypsin Complex Values in Diagnosis of Prostate Cancer: A Cooperative Study , 1998, International journal of urology : official journal of the Japanese Urological Association.

[76]  W. Catalona,et al.  Rate of change in serum prostate specific antigen levels as a method for prostate cancer detection. , 1994, The Journal of urology.

[77]  J. Richie,et al.  Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. , 1994, The Journal of urology.

[78]  J. Oesterling,et al.  Prostate specific antigen: a decade of discovery--what we have learned and where we are going. , 1999, The Journal of urology.

[79]  T. Wilt,et al.  Screening for prostate cancer. , 2013, The Cochrane database of systematic reviews.

[80]  R. Beyth,et al.  Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials , 2010, BMJ : British Medical Journal.

[81]  J. Oesterling,et al.  The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study. , 1992, The Journal of urology.

[82]  M. Becich,et al.  Re: Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: prostate specific antigen is superior to all other clinical parameters. , 1992, The Journal of urology.

[83]  E. Platz,et al.  The influence of statin medications on prostate-specific antigen levels. , 2008, Journal of the National Cancer Institute.

[84]  G. Bubley,et al.  Biology of prostate-specific antigen. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[85]  P. Walsh Screening for prostate cancer. American College of Physicians. , 1997, The Journal of urology.

[86]  E. Klein,et al.  Biochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results. , 1999, Urology.

[87]  J. Oesterling,et al.  The effect of finasteride on prostate specific antigen: review of available data. , 1996, The Journal of urology.

[88]  P. Humphrey,et al.  Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. , 1995, The Journal of urology.

[89]  A. Partin,et al.  Free prostate-specific antigen in serum is becoming more complex. , 2002, Urology.

[90]  J. Potts,et al.  Influence of asymptomatic histologic prostatitis on serum prostate-specific antigen: a prospective study. , 2004, Urology.

[91]  D. Freedman,et al.  Obesity Is Negatively Associated with Prostate-Specific Antigen in U.S. Men, 2001-2004 , 2007, Cancer Epidemiology Biomarkers & Prevention.

[92]  D. Johnston,et al.  The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy. , 2001, The Journal of urology.