Prostate Specific Antigen

The facts about prostate cancer are frightening.
Prostate PSA cancer is the most commonly detected cancer in men in the U.S., affecting approximately 1 out of every 6 men. It is the second leading cause of cancer death among men in the U.S. Although prostate PSA cancer is thought to begin when men are in their thirties or forties, it is more often diagnosed in men over 65 years of age and increases with increasing age. Laboratory testing can assist with screening, diagnosis, staging, prognosis, detection of residual or recurrent disease, and therapeutic monitoring. The primary test used for these purposes is prostate specific antigen (PSA). Prostate PSA is an androgen-regulated, kallikrein-like serine protease produced by normal and malignant epithelium in the prostate, breast, and salivary glands. When secreted into seminal fluid, PSA liquifies the gel-forming proteins in semen. Normal PSA function in breast and salivary glands is unknown.

Other Prostate Cancer testing
Free PSA: This immunoradiometric assay (IRMA) measures the serum level of unbound, or free, PSA. Total PSA is also measured via an equimolar IRMA method and the percentage of free:total PSA is reported.
Total PSA: This microparticle enzyme immunoassay (MEIA) measures the serum level of free and bound PSA in a non-equimolar reaction favoring free PSA. Assay results correlate clinically with those from equimolar assays.

Screening
Prostate cancer screening is valuable because of the high incidence, absence of preventive agents, ease & simplicity of screening, increased detection rates resulting from screening, potential curability of organ-confined disease, and lack of effective therapy for advanced disease.

Prostate Cancer Resources
CapCure http://www.capcure.org/
Prostate Help Association http://www.pha.u-net.com/index.htm
Prostate Health http://www.prostatehealth.com/
Prostate Cancer Institute http://www.prostate-cancer-institute.org/index.html


Diagnosis Information
Prostate cancer diagnosis begins with DRE and total PSA. If either is suggestive of cancer, a transrectal ultrasound (TRUS) guided biopsy is generally the next step. Investigators have attempted to reduce the number of unnecessary biopsies (i.e., enhance the specificity of total PSA testing) without reducing the cancer detection rate. To this end, age-specific PSA reference ranges have been proposed as well as calculations of the prostate specific antigen density (PSAD), PSA velocity, the percentage of free to total PSA (% free PSA), and the percentage of complexed to total PSA (% complexed PSA). Although conflicting studies have been published regarding the benefit of these strategies, guidelines for use and interpretation are provided herein for physicians who want to use them. Serum PSA levels increase with increasing age and prostate size in healthy men. Use of age-related reference ranges theoretically would increase sensitivity in younger men and increase specificity (reducing unnecessary biopsies) in older men. Use of age-related reference ranges has not been widely adopted due to studies demonstrating diminished sensitivity in older men. Some investigators support the use of age-specific ranges only in men younger than 60 years of age.Use of PSAD combines total PSA level with prostate gland volume to assess the probability of a positive biopsy. It is defined as the total PSA divided by the prostate gland volume as determined by TRUS. PSAD has not been widely used owing to lack of consistent evidence regarding clinical benefit. In individuals with pre-clinical prostate cancer, there is an accelerated increase in serum PSA levels, beginning 7 to 9 years prior to diagnosis. Thus, evaluation of the rate of change in PSA levels (PSA velocity) may theoretically assist in early detection of cancer. PSA circulates in both free and bound, or complexed, forms. Immunoreactive PSA is primarily bound to the a1-antichymotrypsin (ACT) protease inhibitor; thus, PSA levels in healthy individuals are comprised mainly of complexed PSA. Individuals with benign prostatic hypertrophy (BPH), though, tend to have lower proportions of complexed PSA (i.e., higher % free PSA) relative to those with prostate cancer. Since the overlap in total PSA levels is substantial among men with BPH and prostate cancer, use of % free PSA may help distinguish those with BPH from those with cancer. Studies have shown improved specificity in men with borderline total PSA levels (4.1-10.0 ng/mL), resulting in a 13-46% reduction in negative biopsies. This improvement was not statistically significant in all the studies however. In men with "normal" PSA levels (2.5 or 3.0 to 4.0 ng/mL), on the other hand, use of % free PSA may increase the sensitivity of PSA by detecting cancers that would have been missed by total PSA alone.