Prostate-Specific Antigen

Prostate-Specific Antigen (PSA) is a glycoprotein found in high concentrations in the prostatic lumen. Significant barriers such as prostate glandular tissue and vascular structure are interposed between the prostatic lumen and the bloodstream. These protective barriers can be broached when disease such as cancer, infection, and benign hypertrophy exists. PSA can be detected in all males; however, levels are greatly increased in patients with prostatic cancer.


Prostate-Specific Antigen test is used as a screening method for early detection of prostatic cancer. When the PSA test is combined with a rectal examination, nearly 90% of clinically significant cancers can be detected. This test is also used to monitor the disease after treatment.


Elevated PSA levels are associated with prostate cancer. Levels greater than 4 ng/mL have been found in more than 80% of men with prostate cancer. The higher the levels, the greater the tumor burden. The PSA assay is also a sensitive test for monitoring response to therapy. Successful surgery, radiation, or hormone therapy is associated with a marked reduction in the PSA blood level. Significant elevation in PSA subsequently indicates the recurrence of prostatic cancer. PSA is more sensitive and specific than other prostatic tumor markers, such as prostatic acid phosphatase (PAP). Also, PSA is more accurate than PAP in monitoring response to therapy and recurrence of tumor after therapy.



Prostate-Specific Antigen testing should be offered to men at the age of 50 years and greater, unless the man has increased risk factors, such as genetic predisposition via family history or African-American racial status. In these “at-risk” men, PSA testing should be offered between 40 and 50 years of age. PSA testing should be performed in conjunction with the digital rectal examination, because the combination of the two tests is more sensitive for diagnosis than either one alone. The U.S. Preventive Services Task Force (USPSTF) is advising against the routine use of PSA testing to screen for prostate cancer in men age 75 and older. This same task force suggests that there is limited benefit from PSA screening in men under the age of 75 who are not considered high risk for prostate cancer. Furthermore, this organization suggests that PSA screening every 4 years is as good as annual PSA testing.


It is important to be aware that some patients with early prostate cancer will not have elevated levels of PSA. It is equally important to recognize that PSA levels above 4 are not always associated with cancer. The PSA is limited by a lack of specificity within the “diagnostic gray zone” of 4 to 10 ng/mL. PSA levels also may be minimally elevated in patients with benign prostatic hypertrophy (BPH) and prostatitis. In an effort to increase the accuracy of PSA testing, other measures of PSA have been proposed. These measurements are:

  • PSA velocity: It is normal for Prostate-Specific Antigen levels to increase as a man ages, PSA velocity is rate in which PSA levels increase over time. A sudden and intense increase in the PSA level means an increase in PSA velocity which raises the possibilities of prostate cancer and can also be a sign of a fast-growing cancer. Statistics show that men whose their PSA increases in a rate   above 0.35 ng/mL per year have a higher risk for dying from prostate cancer than those who have a PSA velocity lower than 0.35 ng/mL a year.
  • Age-adjusted PSA: As mentioned earlier, PSA levels increase every year which causes man’s age to be an important factor that increases PSA levels. Normally, Men younger than age 50 have a PSA level lower than 2.4 ng/mL, on the other hand, men over 70 would have a normal PSA level up to 6.5 ng/mL.
  • PSA Density: It is normal that Prostate-Specific Antigen levels in blood to increase or decrease depending on the prostate size. The larger the prostate size, the higher PSA in the blood. PSA density is a measurement of the relationship between the PSA level and the size of the prostate. The consideration of PSA density is important to correctly interpret PSA findings, especially with patients who have enlarged prostate because the possibility of cancer may be overlooked in such cases. PSA Density can be calculated by knowing the gland volume. There have been several formulas that are developed in order to calculate the normal PSA level by knowing the gland volume. One such volume adjusted formula is:

Expected PSA= 0.12 of Gland Volume in Cubic Centimeters as measured by Ultrasound


  • Free and attached PSA: Prostate-Specific Antigen exist in the peripheral blood in two forms: Free PSA which circulate in the blood without being attached to any other objects, and Attached PSA  which circulate peripheral blood attached to protein molecule. High levels of Free PSA are associated with Benign Prostate Conditions (Benign Prostate Hyperplasia for example). On the other hand, high levels of Attached PSA are associated with prostate cancer which makes the percentage of Free Prostate-Specific Antigen (%FPSA) and important measurement to look at along with PSA levels. Low %FPSA (less than 25%) suggests a higher possibility of Prostate Cancer than BPH.
  • Protein patterns: Studying the patterns of Prostate Proteins is very helpful when the patients Prostate-Specific Antigen levels are high, but not high enough to determine that the condition is Prostate Cancer. A very important protein to look at is the Early Prostate Cancer Antigen (EPCA), EPCA doesn’t exist in healthy prostate cells, it is however found in large amount in cancerous prostate cells. EPCA is more accurate than PSA in diagnosing prostate cancer. EPCA levels are also noticed to increase significantly in conditions where cancer spreads outside the prostate. There are two types Early Prostate Cancer Antigen testing; EPCA-1 and EPCA-2. EPCA-2 is the more commonly used because it is a blood test. EPCA level of 30 ng/mL or higher is a strong indication that the patient is at risk for Prostate Cancer. EPCA-1 on the other hand is a tissue-based test. Another important prostate protein to look at for diagnosing Prostate Cancer is the Prostate-Specific Membrane Antigen (PSMA) which is expressed in all types of prostatic tissue. PSMA is a very useful marker for prostate cancer and it can be also used to monitor the process of treating prostate cancer.


PSA is used in the staging of men with known prostate cancer. Men with PSA levels below 10 ng/mL are most likely to have localized disease and respond well to local therapy (radical prostatectomy or radiation therapy). Routine metastatic staging tests are generally not required for men with clinically localized prostate cancer when their PSA is less than 20 ng/mL.


PSA is used to follow up men after treatment for prostate cancer. Periodic PSA testing should follow any form of treatment for prostate cancer, since PSA levels can indicate need for further treatment. Following curative radical prostatectomy or radiation therapy, PSA levels should probably be 0 to 0.5 ng/mL. The pattern of PSA rise after local therapy for prostate cancer can help distinguish between local recurrence and distant spread. Patients with elevated PSA levels more than 24 months after local treatment and with a PSA doubling time after 12 months are likely to have recurrence.


PSA can be measured by electrochemiluminescent immunoassay, immunohistochemistry, or radioimmunoassay. Newer, comparably accurate, chemical tests are being used to improve the worldwide use of PSA screening testing.




Causes of False Prostate-Specific Antigen Findings

  • Rectal examinations are well known to falsely elevate PAP levels, and they may also minimally elevate the PSA. To avoid this problem, the PSA should be drawn before rectal examination of the prostate or several hours afterward.
  • Prostatic manipulation by biopsy or transurethral resection of the prostate (TURP) will significantly elevate the PSA levels. The blood test should be done before surgery or 6 weeks after manipulation.
  • Ejaculation within 24 hours of blood testing will be associated with elevated PSA levels.
  • Recent urinary tract infection or prostatitis can cause elevations of PSA as much as five times baseline for as long as 6 weeks.
  • Drugs that may decrease PSA levels include Finasteride (Propecia, Proscar) and Diethylstilbesterol (DES).




Indications of Prostate-Specific Antigen Findings

Several factors (the patient’s age for example) should be considered before jumping to conclusions regarding what the PSA findings indicate. Depending on those factors, PSA Levels may have different indications for different patients. The following are the common indications of different PSA levels:

  • Less than or equal to 2.5 ng/mL is Low PSA Level.
  • Between 2.6 and 10 ng/mL is slightly to moderately High PSA Level.
  • Between 10 and 19.9 ng/mL is moderately High PSA Level.
  • More than 20 ng/mL or is significantly High PSA Level.




Causes of High Prostate-Specific Antigen Levels

Prostate-Specific Antigen found in the cytoplasm of diseased prostate is expelled into the bloodstream causing the PSA levels to be elevated. This is an indication of Prostate cancer, Benign Prostatic Hyperplasia (BPH), or Prostatitis.