Greater Boston Urology Blog

Elevated PSA Causes: 3 Reasons Yours Might Be High

Prostate specific antigen (PSA) has a long history as a blood-screening test for prostate cancer. But because of its limitations and relative low sensitivity, there has been a move to find better screening markers for prostate cancer.

While GBU advocates and uses the PSA test, it's important to understand elevated PSA causes, including the fact that PSA can be elevated for reasons other than prostate cancer. These other markers also have limitations but have better parameters in sensitivity, specificity, and predictive values.

Below, we're going to look at age-specific PSA, percent free vs. total PSA, and PSA velocity.

Bottom line: always have an open, honest discussion with your urologist about your options and any questions you have.

As with all content on Greater Boston Urology's blog, the following information is educational in nature, not medical advice. Always talk to your physician about your specific health care questions and conditions.

[Editor's note: This article was reviewed and updated on 7/21/21.]

Age-Specific PSA

As men age, the normal range for PSA changes. In the older man, a higher level PSA is acceptable relative to the younger man due to benign enlargement of the prostate that can occur with age. This benign enlarged prostate releases more PSA into the blood stream than a benign smaller prostate.

Acceptable age ranges:

Up to age 49








(Reference -Oesterling JE, Jacobsen SJ, Chute CG, et al: Serum prostate-specific antigen in a community-based population of healthy men: Establishment of age-specific reference ranges. JAMA 270:860-864, 1993.)

Even with this data, institutions have established their own age-specific guidelines and follow-up protocols. Always discuss test results with your doctor.

Percent Free and Total PSA

PSA is a serine protease that floats freely or is bound to different proteins in the blood. The ratio of free to bound PSA seems to differ in men who have elevated PSA due to either benign or malignant disease.

As such, doctors look at the ratio and use this to help decide whether to recommend a biopsy.

  • The lower the percent free PSA, the more likely the elevated PSA is due to prostate cancer.
  • The higher the percent free PSA, the more likely the elevated PSA is due to benign disease.

PSA Velocity

We have discussed how PSA increases as men age, but we also know that PSA increases as prostate cancer grows in men with cancer. How do we distinguish a "normal" rising rate vs. a "cancerous" rising rate? (This rate of rise over time is known as PSA velocity.)

This question was addressed in the classic study from Johns Hopkins University: The Baltimore Longitudinal Study of Aging.

This study followed many men for years checking PSA on regular intervals. It suggested that for men with PSA of 4-10, a PSA velocity of 0.75ng/ml/year was predictive of a higher risk of prostate cancer.

Because of individual variation in PSA, the researchers determined the PSAs must be drawn over a two-year period with at least three data points. If the PSA was < 4, then a rate of >0.35ng/ml/year should be used (J Natl Cancer Inst 2006;98(21):1521-1527).

In contrast to the above data and NCCN recommendation, a more recent study from Memorial Sloan Kettering Cancer Institute reported that PSA velocity did NOT enhance the ability to diagnose prostate cancer and adding PSA velocity to the current screening approach only added minimal improvement in prostate cancer detection. They found by using this criteria that for about every five men biopsied, only one would detect prostate cancer (J Natl Cancer Inst 2011;103(6):462-469) and decreasing the threshold PSA from 0-2.5 would be a better predictor of prostate cancer.

With this and many other screening test controversies, the best approach remains a multifaceted approach. You should have a discussion with your urologist about the benefits and deficits of screening and possible biopsy based on your individual situation.

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