Dr. Phil's Pearls of Widsom

Updates on Urologic Topics of Interest in the Press -  Helping you become a better informed health care consumer!

PSA
excerpted and modified from ProstateTruth.org with contributions from other referenced sources.

There is so much mystery and confusion surrounding PSA levels, and what that means for you and your prostate gland. Let’s take a close look:

• PSA stands for Prostate Specific Antigen 
• PSA is a protein produced by cells in the prostate gland 
• Elevated PSA Levels are associated with prostate cancer 
• There are many other causes for elevated PSA levels
• PSA does not take the place of the digital rectal exam                                       
• It is recommended by the American Urologic Association
• It is recommended by the American Cancer Society

A quick and simple blood test is all that is needed to check the levels of PSA in your body. It is an incredibly effective way of helping healthcare providers in detecting prostate cancer in its early stages, but it should be noted that an elevated PSA level does not necessarily mean prostate cancer, it is merely the most commonly understood and acceptable (to the public) explanation.

Although the name suggests that PSA is produced and secreted solely by the prostate gland, PSA is produced by other tissues as well-breast tissue, the periurethral glands, parotid gland, and adrenal and renal call tumors-albeit in very low concentrations. (Reference: Partin AW, Hanks GE, Klein EA, et al. Prostate specific antigen as a marker of disease activity in prostate cancer. Oncology 2002; 16:1024-1038, 1042, 1047-1048)

PSA in the body is primarily responsible for liquefaction of semen. Most PSA exists in the blood serum bound to other proteins. The remainder exists in the serum unbound or “free”. The half life of PSA is 2-3 days.

It is believed pathologic processes affecting the prostate gland result in the disruption of membrane barriers within the prostate with resultant “leakage” of PSA into the blood, making it measurable.

It is generally accepted that a healthy, or normal, level for total PSA is under 4.0 nanograms per milliliter of blood. You may just be given, or refer to, a number, and here that would be ‘4’.

Be careful! That upper level of 4.0 can be misleading. As a specialist in Men’s Health and Prostate care, I will tell you that the “4.0” upper limit is in no way “cut in stone” as the “defining number” which tells you and your doctor that you have prostate cancer, or you don’t have cancer. For example, although cancerous prostate tissue releases up to 30 times more PSA in the serum than does benign growing (BPH) tissue, BPH remains the most common cause of elevated PSA levels in the serum.

In my opinion, urologists are unsettled by PSA and recognize the inherent difficulty the serum PSA test presents in clinical practice. For that reason, PSA is looked at in many different ways. Race and age appears to influence PSA. We are able to see differences between age groups and racial groups but are at a loss to explain why. To increase the degree of certainty, various urologists from around the world have looked at establishing age and racial parameters in an effort to identify early prostate cancer victims.

To date, there has not been global acceptance of these criteria presented here for your review.

Age-specific reference ranges have been developed as an additional modality in an attempt to improve the sensitivity and specificity of PSA as a screening tool for Prostate Cancer. This is not without its controversy amongst urologists. Use of age specific PSA ranges may lead to the increased detection of prostate cancer in younger men and therefore those patients are more likely to survive and benefit from early intervention. However, it is criticized by others because of the decreased detection that will occur in older men due to raising the PSA threshold for biopsy higher than the 4.0.

With respect to Race, a similar criticism with respect to having a PSA threshold in excess of 4.0 in an already high risk population is felt to be inappropriate. Others have offered a simpler classification for PSA as a cancer detection tool. It was recommended that there simply be two PSA “normals” for two population groups, >4.0ng/ml for the “general population”, and >2.0ng/ml for the “high-risk population”.

Walter Reed vs. Traditional vs. Mayo Clinic PSA Ranges
Age and Race -Adjusted PSA Reference Ranges for Maximum Detection:

(References:Ricchiutti VS and Resnick MI. Staging of prostate cancer, PSA Issues leading up to prostate biopsy and biopsy technique. Chapter 8, in Prostate Cancer Science and Clinical Practice. Editors: MydloJH and Godec CJ. Academic Press. San Diego, CA 2003. Moul JW Population screening for prosate cancer and early detection in high—risk African American men. Cjapter 1, in Prostate Cancer Science and Clinical Practice. Editors: MydloJH and Godec CJ. Academic Press. San Diego, CA 2003 . Littrup PJ. Editorial: Prostate Cancer in African American men. The Prostate 1997;31:129-41)

Other PSA based tools that are used in clinical practice:

PSA Velocity:
This is a very useful tool and in my practice this is one of the earliest identifiers of “possible” malignant transformation from benign to malignant. The PSA velocity is the rate of change of PSA in the blood stream over a minimum time of 18-24 months. Three repeat PSA’s over this 18-24 month interval optimizes the accuracy of this test. An increase of more than 0.75ng/ml per year identifies a patient at risk and one who should be considered for ultrasound with guided biopsies. Less than 5% of men without prostate cancer will have a PSA velocity >0.75 ng/ml.  (References: Ricchiutti VS and Resnick MI. Staging of prostate cancer, PSA Issues leading up to prostate biopsy and biopsy technique. Chapter 8, in Prostate Cancer Science and Clinical Practice. Editors: MydloJH and Godec CJ. Academic Press. San Diego, CA 2003.)

Free and Complexed PSA:
The standard PSA assay measures the total PSA concentration in the serum i.e., “complexed” and “free” PSA fractions. Approximately 60-75% of the PSA found in the circulation is “complexed” with proteins and inhibitors, leaving approximately 30-40% unbound or “free” in the blood. Compared with healthy men and those with BPH, men with prostate cancer are more likely to have less free PSA (<25%). Men with a higher likelihood of having prostate cancer will therefore have more complexed PSA. It is most useful in those cases where the PSA is between 4.0-10.0 ng/ml. (Reference: Carter HB, DeMarzo AM, Lilja H. Chapter 1 Detection, diagnosis, and prognosis of prostate cancer in Report to the Nation on Prostate Cancer 2004. Carroll PR and Nelson WG (eds) Prostate Cancer Foundation, Santa Monica, CA 2004.)

Potential Causes of Changes in PSA:

The following elevates PSA:

• Benign Prostatic Hypertrophy (BPH)
• Prostate Cancer
• Prostatitis
• Physical Manipulations of the prostate:
  The following cause a spike in the level of “Free PSA”. The total PSA is not affected by these; Free PSA levels return to normal in a few days:
  • Digital Rectal Exam (DRE)
  • Transrectal Ultrasound of Prostate (TRUS-P)
  • Urethral catheterization
• Urinary Retention
• Ejaculation
• Pelvic Trauma
• Prostate Needle Biopsy
• Prostate Ultrasound for Volume
• Black Race

The following reduces PSA:

• Relief of Urinary Retention
• Finasteride (Proscar)
• Dutasteride(Avodart)
• Prostate Cancer therapies:
  • PCSpes (Herbal Supplement)
  • LHRH Agonists i.e., Lupron and  Zoladex
  • Antiandrogens i.e., Casodex, Flutamide

If you have further questions, please don’t hesitate to print this and bring it in. We will be more than happy to review this with you at your next office visit  at Main Urology!