More men sit in my waiting room over this number than any other, and most were never told what it actually measures.
Prostate Specific Antigen, or PSA, is a protein produced by prostate cells. It goes up as men age, when the prostate enlarges, when the prostate is inflamed, and when prostate cancer is present. It also bumps up temporarily after a digital rectal exam, after ejaculation, and after bike riding.
That last list is the whole problem in a nutshell. PSA is prostate specific, but it is not cancer specific. A single number read on its own tells you less than most people assume, and there are several different ways to look at it.
Absolute value
When PSA came into use, a cutoff of 4.0 was chosen to strike an acceptable balance between sensitivity, meaning how many cancers it catches, and specificity, meaning how often a positive result is real.
We learned fairly quickly that one number for every man does not work. A 4.0 cutoff missed too many cancers in younger men, and in older men it produced too many biopsies and too much diagnosis of disease that was never going to cause harm.
Age-based ranges
PSA rises with age, so it makes sense to expect less of it in a younger man. Using a lower threshold in younger men catches cancers earlier, and a higher threshold in older men avoids a great many unnecessary biopsies. Several reference ranges are in use. One of the more common:
| Age | Upper limit |
|---|---|
| 46–55 | 2.5 |
| 56–65 | 3.5 |
| 66–75 | 4.5 |
| Over 75 | 6.5 |
Free and total PSA
PSA circulates in more than one form. Some of it floats free and some is bound to other proteins.
Benign conditions tend to produce a higher proportion of free PSA, above about 25 percent. Prostate cancer tends to produce less, below about 15 percent. That helps stratify risk. If a man has a PSA of 8.0 and a negative biopsy, knowing his free PSA is above 25 percent gives real reassurance that he does not have cancer.
PSA density
PSA rises as the prostate gets bigger, so big prostates make more PSA. A normal prostate is around 25 grams; we consider anything over 40 grams enlarged. Roughly, expect about 0.1 of PSA per gram, which is why a 40 gram prostate lines up neatly with an upper limit of 4.0.
This one has become more useful than it used to be, not less. We are less worried about a PSA of 6.0 in a man with a 60-gram prostate. We are considerably more worried about a PSA of 4.2 in a 17-gram prostate. And because MRI now gives us an accurate prostate volume as a matter of course, density is easy to calculate and is used routinely to help decide who actually needs a biopsy.
PSA velocity
Velocity is the rate at which your PSA rises over time. The logic is intuitive: a PSA that goes 5.0, then 5.1, then 5.2 is less concerning than one that goes 1.0, then 2.0, then 4.0.
I made more of this one in the original version of this post than I would now. Guidelines have moved away from treating velocity as a reason to biopsy on its own. Individual PSA measurements bounce around more than people expect, and a rising trend across a few draws often turns out to be noise or inflammation rather than cancer.
A rising PSA is still worth paying attention to, and it is a reason to look more carefully. By itself it is not a reason to go to a needle.
What actually happens after an elevated PSA
This is the part that has changed most since 2016, and most of it is good news.
An elevated PSA no longer sends you straight to biopsy. The usual next step is an MRI of the prostate. A reassuring MRI can mean no biopsy at all. A suspicious one lets us aim at the specific area of concern rather than sampling blindly, which finds the cancers that matter and misses fewer of them.
There are also blood and urine tests (the 4Kscore, PHI and SelectMDx among them) that refine the odds before anyone commits to a biopsy. They are not perfect and they are not always necessary, but they give us another way to avoid a procedure a man does not need.
When a biopsy is warranted, more of them are now done through the perineum rather than through the rectum, which lowers the risk of infection quite a bit.
And if it is cancer
The old argument against PSA screening rested on overtreatment. It was a fair argument at the time. It is much weaker now.
Low risk prostate cancer today is usually not treated. It is watched, with periodic PSA, imaging and repeat biopsy when indicated, and surgery or radiation held back for the cancers that prove they need it. That approach is called active surveillance. It broke the link between finding a small cancer and getting an operation you did not need.
The summary
PSA is a tool. It is far from perfect, and it is useful when a patient and physician use it together to make a decision instead of treating one number as a verdict.
Since PSA screening began, the death rate from prostate cancer has fallen substantially. [verify current figure] Prostate cancer remains one of the leading cancer killers of men in the United States. [verify current ranking] There is still plenty left to learn.
Get as much information as you reasonably can, understand what each piece does and does not tell you, and make the decision with your doctor. I know that sounds like a dodge. With this test it happens to be the right answer.