The Meaning of PSA

As men get older, they almost all develop enlargement of the prostate.  Invariably, PSA rises as a result.  PSA comes both from the prostate gland and potentially, in some cases, from prostate cancer.  This what confuses things.  PSA can come from both cancer and the benign prostate gland. So when checking PSA, the question should never be, "Is it above a pre-specified arbitrary threshold such as 2.5 or 4.0?" The question should be, "Is the PSA elevated above what should be expected based on the size of the prostate?"

The size of a man’s prostate can be estimated by digital rectal examination by a well-trained doctor.  However, in my experience, very few physicians are skillful at estimating prostate size by digital examination.  Therefore, in most cases prostate size can only be determined by measuring it with an ultrasound or MRI.  Ultrasound can be performed in the doctor’s office by a urologist.  MRI is usually performed at a specialized imaging center.  Modern prostate MRI imaging technology, termed 3-T multi-parametric MRI, is gaining in popularity and becoming more widely available.   

Once the size of the prostate gland has been ascertained by imaging, the expected normal PSA for that individual can be calculated.  Typically, PSA rises one point for each 10 cubic centimeters (cc) of prostate volume.  Therefore, the formula for calculating how the PSA relates to the prostate’s size in normal person works by dividing the prostate volume by 10.

 For example, for a 30cc prostate the normal PSA should be around 3; for a 50cc prostate, around 5.  A man with a 100cc prostate will have a normal PSA of approximately 10.

The PSA level becomes abnormal when it’s 50% higher than what would be expected - based on the prostate’s size.  For example, an “abnormal” PSA for a man with a 30cc prostate is 4.5 or above.

  Abnormal PSA for a 50cc prostate is above 7.5.  For a 100cc gland, PSA would need to be above 15 to create a concern. In the medical textbooks this ratio of prostate gland size to PSA is called PSA density.  Until you determine the size of the prostate gland, unless the PSA level is off the charts, say over 20, you really can't draw any conclusions about how the PSA may pertain to the risk of underlying prostate cancer.

There are also other possibilities to explain why the PSA may be elevated besides cancer or having an enlarged prostate gland.  Temporary increases can occur from recent sexual activity, prolonged bicycle riding and from nonspecific prostatitis.  PSA levels that seem unexpectedly high should always be repeated can confirmed before embarking on further action.

Nonspecific, subclinical prostatitis is a very common cause of PSA elevation in the general male population.  Infections of the prostate gland serious enough to cause men to feel ill with pelvic pain and fever, also called prostatitis, are rather uncommon.

  However, subclinical infection of the prostate gland, a condition that men are generally unaware of, occurs in almost all men at some point in their lives.  Some experts suspect that these subclinical infections are the root cause of prostate enlargement but this connection has not been established with certainty. 

The important thing about prostatitis to know is that this silent inflammatory process frequently causes PSA levels to elevate, creating all kinds of confusions and consternation about the possibility of underlying prostate cancer.  Unfortunately, simple treatments to reliably alleviate inflammation do not exist.  Sometimes antibiotics are tried but frequently they are ineffective or the PSA decline is temporary.  Much further research is needed into figure out how to effectively manage this common problem.

By imaging the prostate and accurately determining its size, we can put PSA into a meaningful context.  PSA has been a very useful test, but unfortunately, forgetting how much variation there is in the size of men's prostate glands often leads to unnecessary random biopsy.  Since PSA levels are affected by the size of the prostate, finding an oversized gland can be good news.  It provides a benign explanation for why the PSA level is running high and helps reduce the need for doing a biopsy.

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