Highly preserved in the evolution chain, prostate-specific antigen (PSA) is a serine protease elaborated, almost exclusively, by the epithelial cells lining the acini and ducts of the prostate gland. Once produced, it is secreted into the prostatic ductal system and is present in high concentrations in the seminal plasma, in which it serves the purpose of liquefying the seminal coagulum.42 Oesterling J.E. Prostate specific antigen: A critical assessment of the most useful tumor marker for adenocarcinoma of the prostate J Urol 1991 ; 145 : 907
Cliccare qui per andare alla sezione Riferimenti, 52 Sensabaugh G.F. Isolation and characterization of a semen-specific protein from human seminal plasma: A potential new marker for semen identification J Forensic Sci 1978 ; 23 : 106
Cliccare qui per andare alla sezione Riferimenti Since its isolation and identification in the human serum, prostatic fluid, and tissue nearly 2 decades ago, PSA has been under intensive investigation by the urologic community.34 Hara M., Inorre T., Fukuyama T. Some physico-chemical characteristics of gamma-seminoprotein, an antigenic component specific for human seminal plasma Japanese Journal of Legal Medicine 1971 ; 5 : 322
Cliccare qui per andare alla sezione Riferimenti, 39 Li T.S., Beling C.G. Isolation and characterization of two specific antigen of human seminal plasma Fretil Steril 1973 ; 24 : 134
Cliccare qui per andare alla sezione Riferimenti, 58 Wang M.C., Valenzuela I.A., Murphy G.P. , e al. Purification of a human prostate specific antigen Investig Urol 1979 ; 17 : 159
Cliccare qui per andare alla sezione Riferimenti Today, as a result of such efforts and because of its unique characteristics, PSA has been established as the most clinically useful tumor marker for mass screening, diagnosis, staging, and monitoring of prostate cancer.42 Oesterling J.E. Prostate specific antigen: A critical assessment of the most useful tumor marker for adenocarcinoma of the prostate J Urol 1991 ; 145 : 907
Cliccare qui per andare alla sezione Riferimenti, 46 Partin A.W., Oesterling J.E. The clinical usefulness of prostate specific antigen: Update J Urol 1994 ; 143 : 1358
Cliccare qui per andare alla sezione Riferimenti
Used classically as a follow-up marker for patients who had undergone treatment for adenocarcinoma of the prostate, measurement of serum PSA in more recent years has been strongly advocated and widely used by some authors as a screening test for this malignancy.17 Catalona W.J., Smith D.S., Ratliff T.L. , e al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer N Engl J Med 1991 ; 324 : 1156 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti, 25 Crawford E.D., DeAntoni E.P. PSA as a screening test for prostate cancer Urol Clin North Am 1993 ; 20 : 637
Cliccare qui per andare alla sezione Riferimenti Though unique, PSA has important shortcomings that prevent it from being the ideal tumor marker.10 Brawer M.K., Lange P.H. PSA in the screening, staging, and follow-up of early prostate cancer: A review of recent developments World J Urol 1989 ; 7 : 7 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti, 27 Ercole C.J., Lange P.H., Mathisen M. Prostate specific antigen and prostatic acid phosphatase in the monitoring and staging of prostate cancer J Urol 1987 ; 138 : 1181
Cliccare qui per andare alla sezione Riferimenti, 35 Hudson M.A., Bahnson R.R., Catalona W.J. Clinical use of prostate specific antigen in patients with prostate cancer J Urol 1989 ; 142 : 1011
Cliccare qui per andare alla sezione Riferimenti, 43 Oesterling J.E., Chan D.W., Epstein J.I. Prostate specific antigen in the preoperative and postoperative evaluation of localized prostate cancer treated with radical prostatectomy J Urol 1988 ; 139 : 766
Cliccare qui per andare alla sezione Riferimenti, 47 Partin A.W., Carter H.B., Chan D.W. , e al. Prostate specific antigen in the staging of localized prostate cancer: Influence of tumor differentiation, tumor volume, and benign hyperplasia J Urol 1990 ; 143 : 747
Cliccare qui per andare alla sezione Riferimenti, 55 Stamey T.A., Yang N., Hay A.R. , e al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate N Engl J Med 1987 ; 317 : 909 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti Although organ-specific, PSA is not cancer-specific, resulting in a limitation of the marker's ability to differentiate PSA abnormalities owing to prostate malignancy from a series of benign and more prevalent conditions that frequently can produce elevations in serum PSA concentrations, such as benign prostatic hyperplasia (BPH), acute prostatitis, acute urinary retention, and prostatic ischemia.28 Glenski W.J., Malek R.S., Myrtle J.F. , e al. Sustained substantially increased concentration of prostate specific-antigen in the absence of prostatic malignant disease: An unusual clinical scenario Mayo Clin Proc 1992 ; 67 : 249
Cliccare qui per andare alla sezione Riferimenti, 42 Oesterling J.E. Prostate specific antigen: A critical assessment of the most useful tumor marker for adenocarcinoma of the prostate J Urol 1991 ; 145 : 907
Cliccare qui per andare alla sezione Riferimenti, 49 Robles J.M., Morell A.R., Redorta J.P. , e al. Clinical behavior of prostatic specific antigen and prostatic acid phosphatase: A comparative study Eur Urol 1988 ; 14 : 360
Cliccare qui per andare alla sezione Riferimenti Noteworthy also is the finding that serum PSA elevation is not always observed in men with prostate cancer.
Several studies have shown that the median PSA concentration is significantly and consistently higher for men with organ-confined prostate cancer than for men with BPH.44 Oesterling J.E., Cooner W.H., Jacobsen S.J. , e al. Influence of patient age on serum PSA concentration Urol Clin North Am 1993 ; 20 : 671
Cliccare qui per andare alla sezione Riferimenti, 53 Sershon P.D., Barry M.J., Oesterling J.E. Serum PSA values in men with histologically confirmed BPH versus patients with organ-confined prostate cancer [abstract] J Urol 1993 ; 149 : 421A
Cliccare qui per andare alla sezione Riferimenti Using a cut-off point of 4.0 ng/mL, however, most of these studies have shown a considerable overlap in PSA values between these two pathologies. Because of the lack of sensitivity (68% to 80%) and specificity (49% to 90%) well documented by these reports, the value of PSA measurement in routine mass screening and its adequacy as a tumor marker for the early detection of prostate cancer has been questioned.5 Babaian R.J., Fritsche H.A., Evans R.B. Prostate specific antigen and the prostate gland volume: Correlation and clinical application J Clin Lab Anal 1990 ; 4 : 135 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti, 19 Chan D.W., Bruzek D.J., Oesterling J.E. , e al. Prostate specific antigen as a marker for prostatic cancer: A monoclonal and polyclonal immunoassay compared Clin Chem 1987 ; 33 : 1916
Cliccare qui per andare alla sezione Riferimenti, 33 Guinan P., Bhatti R., Ray P. An evaluation of prostate specific antigen in prostatic cancer J Urol 1987 ; 137 : 686
Cliccare qui per andare alla sezione Riferimenti, 38 Lange P.H., Brawer M.K. Serum prostate-specific antigen: Its use in diagnosis and management of prostate cancer Urology 1989 ; 33 (suppl) : 13
Cliccare qui per andare alla sezione Riferimenti, 55 Stamey T.A., Yang N., Hay A.R. , e al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate N Engl J Med 1987 ; 317 : 909 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti
This lack of accuracy is most striking for the subgroup of patients whose PSA values lie between 4.1 and 10.0 ng/mL, in which range the aforementioned overlapping results most frequently are found and also many patients with organ-confined disease are likely to be located. Many of these patients undergo prostatic transrectal ultrasonography (TRUS) and prostate biopsy to determine the cause of their PSA elevation.22 Cooner W.H., Mosley B.R., Rutherford C.L. , e al. Clinical application of transrectal ultrasonography and prostate specific antigen in the search for prostate cancer J Urol 1988 ; 139 : 758
Cliccare qui per andare alla sezione Riferimenti, 23 Cooner W.H., Mosley B.R., Rutherford C.L. , e al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination, and prostate specific antigen J Urol 1990 ; 143 : 1146
Cliccare qui per andare alla sezione Riferimenti, 59 Waterhouse R.L., Resnick M.I. The use of transrectal prostatic ultrasonography in the evaluation of patients prostatic carcinoma J Urol 1989 ; 141 : 233
Cliccare qui per andare alla sezione Riferimenti For the population whose PSA is 4.0 ng/mL or less, there is a low prevalence of prostate malignancy (1.4%), whereas if PSA is greater than 10.0 ng/mL, a high prevalence is verified (53.3%).5 Babaian R.J., Fritsche H.A., Evans R.B. Prostate specific antigen and the prostate gland volume: Correlation and clinical application J Clin Lab Anal 1990 ; 4 : 135 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti, 21 Cooner W.H. Prostate-specific antigen, digital rectal examination, and transrectal ultrasonic examination of the prostate in prostate cancer detection Monogr Urol 1991 ; 12 : 3
Cliccare qui per andare alla sezione Riferimenti
Researchers have undertaken the task of improving the ability of serum PSA measurement to detect organ-confined prostate cancer. To do so, it is necessary to enhance the capability of this tumor marker to distinguish reliably BPH from clinically significant, nonpalpable prostate cancer, assuming the fact that larger lesions can be detected by digital rectal examination (DRE), and consequently serum PSA is not required for their diagnoses. As a result, in recent years several concepts have been developed and proposed and are being tested clinically with the purpose of optimizing the clinical use of PSA by improving its specificity and preserving its sensitivity. These new techniques include PSA density (PSAD), PSA velocity, age-specific PSA, and percent free PSA.4 Babaian R.J., Miyashita H., Evans R.B. , e al. The distribution of prostate specific antigen in men without clinical or pathological evidence of prostate cancer: Relationship to gland volume and age J Urol 1992 ; 147 : 837
Cliccare qui per andare alla sezione Riferimenti, 9 Benson M.C., Whang I.S., Pontuk A. , e al. Prostate specific antigen density: A means of distinguishing benign prostatic hypertrophy and prostate cancer J Urol 1992 ; 147 : 815
Cliccare qui per andare alla sezione Riferimenti, 14 Carter H.B., Pearson J.D., Metter E.J. , e al. Longitudinal evaluation of prostate specific antigen levels in men with and without prostate disease JAMA 1992 ; 267 : 2215
Cliccare qui per andare alla sezione Riferimenti, 18 Catalona W.J., Smith D.S., Wolfert R.L. , e al. Evaluation of the percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening JAMA 1995 ; 274 : 124
Cliccare qui per andare alla sezione Riferimenti, 44 Oesterling J.E., Cooner W.H., Jacobsen S.J. , e al. Influence of patient age on serum PSA concentration Urol Clin North Am 1993 ; 20 : 671
Cliccare qui per andare alla sezione Riferimenti, 45 Oesterling J.E., Jacobsen S.J., Chute C.G. , e al. Serum prostate-specific antigen in a community-based population of healthy men: Establishment of age-specific reference ranges JAMA 1993 ; 270 : 860
Cliccare qui per andare alla sezione Riferimenti, 55 Stamey T.A., Yang N., Hay A.R. , e al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate N Engl J Med 1987 ; 317 : 909 [cross-ref]
Cliccare qui per andare alla sezione Riferimenti, 56 Stenman U.H., Leinonen J., Alfthan H. , e al. A complex between prostate-specific antigen and alpha-1-antichymotrypsin is the major form of prostate-specific antigen in the serum of patients with prostate cancer Cancer Res 1991 ; 51 : 222
Cliccare qui per andare alla sezione Riferimenti Most of these concepts are still under evaluation to determine their true clinical usefulness. Their specific features are discussed separately elsewhere in this issue. In this article PSA density is reviewed in its concept, application, and results in the assessment and management of the male population at risk of harboring prostate cancer.
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