Evaluating PSA Levels in Men on Oral Medication to Treat Prostate Disease

Benign prostatic hyperplasia (BPH) is a common health condition in men, affecting about 50 percent of men by the age of 60. Severity is highly variable but increases with age. Lower urinary tract symptoms (LUTS) associated with BPH substantially impact a man's daily life and his psychological well-being. BPH may lead to a severe condition known as acute urinary retention in a significant number of younger men, and dramatically increases to nearly 10 percent of men in their 70s over a five year period.1

Men diagnosed with BPH may be prescribed alpha-1-blockers, 5-alpha-reductase inhibitors (5ARIs) or both drugs for medical treatment of their condition. Combination therapy with doxazosin and finasteride has recently been shown to significantly reduce the risk of BPH progression over the use of either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.2

Using a 5-alpha-reductase inhibitor (5ARI) like Finasteride treats the underlying cause of BPH symptoms by gradually shrinking the prostate gland over many months of?Therapy.3 The levels of serum PSA in most men on the same dose (five mg/day) of 5ARI eventually decline by 20 percent to greater than 60 percent, generally reflecting the smaller size of the prostate gland. As a result, investigators have suggested doubling PSA results to retain PSA's role in guiding follow-up testing and procedures.3 However, the use of arbitrary mathematical factors is potentially highly unreliable in men being treated with 5ARIs.

In the July 17, 2003, issue of the New England Journal of Medicine, a seven-year study?showed a 25 percent reduction in prostate cancer for those patients on finasteride. This finding has prompted discussions about the possible use of 5ARIs in healthy men for prostate cancer chemoprevention, making interpretation of PSA levels more complex for a larger group of men. Patient noncompliance in this study was detected at 14.5 percent, representing another possible source of uncertainty in interpretation of PSA levels.4

In clinical studies containing large numbers of BPH patients on finasteride, the median change in total-PSA level appears to be predictable. However, changes in individual patients ranges from -81 percent to +20 percent. Men placed on 5ARI therapy need to be monitored carefully with a reliable means of detecting prostate cancer. The decrease in total PSA with finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and Act PSA. This explains why the ratio of free PSA to total PSA does not change significantly with finasteride treatment.5 Preliminary studies that have shown percent-free PSA (free PSA/total PSA) does not change significantly during 5-ARI therapy, need additional investigation to address the question of whether percent-free PSA can help normalize the impact of 5ARIs on PSA levels and prostate cancer detection.6

References

1. Jacobson S, et al, Natural History of Prostatism: Risk Factors for Acute Urinary Retention, The Journal of Urology, Vol 158, p 481-487, Aug, 1997

2. McConnell J D, et al, The Long-Term Effect of Doxazosin, Finasteride and Combination Therapy on the Clinical Progression of BPH, New Eng. J. of Med.Vol 349, No 25, 2387-98, Dec. 18, 2003

3. Brawer M, et al, Effect of Finasteride and /or Terazosin on Serum PSA: Results of Cooperative Study # 359, The Prostate, 39, p 234-239, 1999

4. Thompson, I M, et al, The Influence of Finasteride on the Development of Prostate Cancer, New Eng. J. of Med., Vol 349, No 3, p 213-222, July 17, 2003

5. Espana F, et al, Changes in Molecular Forms of PSA During Treatment with Finasteride, BJU International, Vol 90, p 672-677, 2002

6. Pannek, J et al, Influence of Finasteride on Free and Total Serum PSA Levels in Men with BPH, The Journal of Urology, Vol 159, p 449-453, February 1998