(PSA is a frequent subject in QUEST. Please use the website search engine for additional coverage if this topic. Also, please see QUEST, Spring 2004, The PSA Story: It’s A Lot More Than A PSA Score and QUEST, Winter 2004, Dr. Catalona Responds to Stories and Studies About Use of PSA Testing.)

1. Q: What is so special about the PSA test?
A: The PSA blood test is probably the single most accurate test we have for the detection of prostate cancer. PSA is a protein that’s produced in the prostate gland. Normally, the PSA should be very low in the bloodstream.

Our studies showed that the median PSA level is 0.7 for men in their 40s, 0.9 for men in their 50s and 1.4 for men in their 60s.

If the prostate is diseased – from benign enlargement, inflammation, or prostate cancer – the PSA is elevated.

If it’s diseased, the elevated PSA is like the red light going on in the cockpit of an airplane. It indicates that there is something wrong in the prostate gland. It may not be prostate cancer; it may be a benign condition, but there’s something going on there that needs further evaluation, which usually means a biopsy of the prostate. Nevertheless, the higher the PSA level, the more likely that a man has prostate cancer and the more likely that it will be aggressive and need treatment.

The PSA is not a perfect test. Initially, people were hoping for something like a pregnancy test. If the test was positive, the patient always had cancer, and when it was negative, the patient never had cancer. That’s almost too much to ask of any medical test. When used properly, the PSA test can detect prostate cancer in a curable stage in the great majority of patients.

2. Q: What is the range of PSA from normal to high?
A: Rather than consider the PSA range in terms of "normal or abnormal," it is more useful to consider it as a means of assessing the risk that prostate cancer would be found on a biopsy.

For instance, regardless of age, if a man has a perfectly healthy prostate gland (without inflammation, benign enlargement or cancer) the PSA should be very low - certainly less than 2. Our studies showed than the median PSA level is 0.7 for men in their 40s, 0.9 for men in their 50s and 1.4 for men in their 60s.

If there is cancer, inflammation, or benign enlargement, or a combination of these conditions, the PSA level will be higher.

If the PSA is in the 2.5-4 range, the chances of finding cancer on biopsy are about 25%. If the PSA is 4-10, the chances of finding cancer are 35-40%. If the PSA is higher than 10, the chances of finding cancer are about 60%.

With cancer and benign enlargement, the PSA levels always go up and never come down on their own. With inflammation, PSA levels go up with a flare-up and come back down with resolution of the inflammation.

There are other tests that help discriminate between elevations caused by prostate cancer and those caused by other benign conditions. These include PSA rate of change, PSA indexed to the prostate volume, and measurements of free or complexed PSA.

In general, the more rapidly the PSA rises, the more likely there is cancer, except for very dramatic rises of more than 2ng/ml per year that are more likely to be caused by inflammation in the prostate gland (prostatitis).

3. Q: At what age should a man be checked for prostate cancer?
A: Recent studies have caused me to believe that men should have an initial PSA test earlier than I previously recommended.

All men should have an annual PSA test and a digital rectal exam beginning at age 40 to assess their risk of having prostate cancer or developing prostate cancer in the future. And if men have a family history of early age-at-onset prostate cancer, then the PSA should be tested at 35.

I recommend biopsy for a suspicious DRE or a PSA of more than 2.5. Also, I recommend that PSA velocity be considered in biopsy decisions.

Some doctors do not recommend a biopsy if the PSA is over 2.5 or even if it is over 4. (Again, my recommendation is biopsy with a PSA 2.5 or over.) However, if the PSA velocity is higher than 0.5 ng/ml/year in a man whose total PSA is below four or if the PSA velocity is higher than 0.75 in a man with a PSA higher than 4, it is even more important to have a prostate biopsy.

An important caveat is that very dramatic increases in PSA (more than 2 ng/ml/year) are more likely to be caused by prostatitis rather than prostate cancer.

Also, in patients who have had a prior biopsy for a PSA over 2.5 or over 4.0 and the biopsy was negative for cancer, a rising PSA makes a case for repeating the biopsy procedure.

These recommendations are similar to the 2004 National Comprehensive Cancer Center Network guidelines.

4. Q: Does Medicare or Medicaid cover the PSA screening test?
A: Yes. By congressional act, all Medicare and Medicaid patients can receive an annual PSA test as part of their benefits.

5. Q: What could cause a PSA level to raise other than cancer?
A: The following can cause the PSA to rise: cancer, benign enlargement, and inflammation (prostatitis) of the prostate, or infection of the urinary tract.

With cancer and benign enlargement, the PSA goes up persistently; the slope is steeper with cancer. With infection, the PSA can rise with a flare-up and come back down with resolution of the inflammation.

A first response to an elevated PSA is an initial two-week prescription of CIPRO, the medication for treatment of an infection in the urinary tract or prostate gland. If, after taking CIPRO, the PSA lowers and stays low, then the cause of the elevated PSA was an infection.

Interpreting the PSA pattern is complicated because some patients have two or three conditions at the same time. If CIPRO results in a lower PSA, I would still recommend retesting in 3 months and consider a prostate biopsy if the PSA has risen again or remains high with respect to the median value for the age group.

6. Q: What does it mean when a PSA is in the normal range even though it has risen a significant percentage since the prior year? What is PSA Velocity? (also see QUEST, Fall2004, PSA Velocity: Important New Tool in Fight Against Prostate Cancer)
A: It is important to realize that PSA levels may fluctuate from 10-15% between readings. With prostate cancer, PSA levels usually increase about 20% per year, depending upon the growth rate of the tumor.

The rate of rise in PSA level is called PSA Velocity and we now think it could be one of the most important indicators of prostate cancer and the aggressiveness of the prostate cancer.

A persistently rising PSA level can be an indication of prostate cancer, even if the absolute level is within the “normal” range. On the other hand, very dramatic rises in PSA of greater than 2ng/ml per year are more likely to be caused by prostatitis.

7. Q: What is the free PSA test? (also see QUEST, Winter 2000, Free PSA Test Helps in Prostate Cancer Diagnosis)
A: PSA exists in the blood in two forms: one is free floating (free) and the other is attached to proteins.

In patients with PSA elevations due to cancer, more of the PSA is in the attached form and less is in the free form.

In patients with PSA elevations due to benign conditions such as benign enlargement or inflammation, more PSA is in the free form.

Thus, in patients whose PSA values are in the gray zone (2.5-10) in terms of prostate cancer risk, the percentage of PSA that is free and that is attached helps to evaluate the risk of prostate cancer.

For example, if the total PSA is between 4 and 10 and the % free PSA is over 25%, there is only an 8% chance that a biopsy would show cancer. On the other hand, if the % free PSA is less than 10%, the chances for prostate cancer would be almost 60%.

One of the problems with PSA blood tests is that if the PSA level is elevated, about 25 to 60 percent (depending on how high the PSA level is) of those men are actually found to have prostate cancer. That means roughly 40% to 80% of men who have elevated PSA levels don’t have prostate cancer and they go through the biopsy unnecessarily.

The free PSA blood test can eliminate at least 20 percent of these biopsies and still detect 95 percent of these cancers.

8. Q: Is there a relation between prostate size and PSA?
A: Yes. Usually, the larger the prostate gland, the higher the PSA. The ratio of serum PSA to prostate volume is called PSA density. If the density is greater than 0.1, there is a suspicion of cancer. A lower density is most consistent with benign enlargement but does not absolutely rule out prostate cancer.

9. Q: What do PSA values show after a radical prostatectomy? (For many more Q&As on this topic, see FAQ on PSA After Treatment for CaP and Recurrence Treatments)
A: After the prostate gland has been completely removed, any PSA in the blood is produced by prostate cancer cells that have left the prostate gland and spread to other areas of the body. However, sometimes the PSA can appear to be elevated because of a laboratory error.

All elevated PSA levels after surgery should be re-checked to rule out a laboratory error.

For practical purposes, it is very difficult to detect PSA in tests when the levels are less than 0.2 ng/ml; therefore, any PSA value less than 0.2 is considered negligible. Hence, a value of 0.2 ng/ml or 0.1 ng/ml would be considered essentially zero. (Other prostate cancer treatments might have different time-frames for post-treatment PSA values, but at some point, the PSA value of more than 0.2 indicates a possibility if recurrence.

10. Q: Is PSA Testing creating a high rate of overdetection of prostate cancer?
A: Clearly, early detection of prostate cancer is going to have more potential benefit for men in their 50s and early 60s because of their life expectancy. It is harder to show a benefit in older men who are more likely to die of another cause first. But with age expectancy rising, the definition of older men is also changing.

In addition, many older men develop aggressive prostate cancer that ultimately kills them in a very painful way. Early detection and some form of treatment can help prevent that outcome as well.

Statistical models for overdetection do not take into consideration the clinical judgment of a well-informed doctor and patient regarding the risk-benefit ratio of screening and treatment for prostate cancer.

Knowledge is useful, and it is usually beneficial to know whether cancer is likely to be present and whether there are signs of progression, such as a rising PSA level, so appropriate intervention can take place, if indicated. Some “overdetection” takes place with any cancer-screening program, but good clinical judgment can usually prevent this occurrence from harming the patient.

It is easier to call overdetection in patients with a short life expectancy than in patients with a long life expectancy. In a young patient with a very long life expectancy, it is not possible to say with certainty that a prostate cancer does not have or will not acquire the capacity to cause disability and/or death.

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