What’s the best way to screen for prostate cancer (PCa)? It’s the PSA test, right? Well, not exactly.

What is PSA?

PSA stands for prostate specific antigen, a protein produced by prostate cells. PSA is “shed” into the bloodstream, and a simple blood test measures the amount. It is reported as a concentration, that is, how many nanograms (ng) per milliliter (ml) of blood, or ng/ml. The more PSA, the higher the number.

All healthy prostate cells produce PSA. As a man ages, the prostate tends to produce more cells. This noncancerous condition is called benign prostatic hyperplasia (BPH). These extra cells also produce PSA. An older man’s PSA is typically higher than a younger man’s. It’s normal, and nothing to worry about.

Is there a normal PSA for everyone?

PSA varies by age. Here is a chart from the Cleveland Clinic showing average normal PSA by age:

Age	Normal PSA Level (ng/ml)	Abnormal Level (ng/ml)
40 to 50	0 to 2.5	Higher than 2.5
50 to 60	2.5 to 3.5	Higher than 3.5
60 to 70	3.5 to 4.5	Higher than 4.5
70 to 80	4.5 to 5.5	Higher than 5.5

Does an abnormally high PSA mean cancer?

An abnormally high PSA may mean PCa. Cancerous prostate cells also produce PSA, because they are mutations of normal prostate cells. The abnormal structure of these cells allows more PSA to “leak” into the blood. Therefore, it’s more accurate to say that an abnormally high PSA is suspicious for PCa.

However, it does not automatically mean cancer, because other conditions that stimulate the prostate can cause more PSA to be released. These are things like prostatitis or infection, sexual orgasm, riding a bike, a digital rectal exam, a large amount of BPH, etc.

How do you know what a high PSA means?

There is a problem determining exactly what an abnormally high PSA means. Until fairly recently, the only way to clarify it was a prostate biopsy, but going from PSA directly to biopsy brought harms:

• A negative biopsy either meant no PCa (unnecessary biopsy) or the biopsy needles missed PCa that needed immediate treatment (underdetection).
• Biopsies picked up PCa that didn’t need immediate treatment (overdetection).
• A biopsy using 12 or more needles increases risk of infection and other side effects.
• Many patients with insignificant PCa were overtreated, leaving many with urinary, sexual or bowel side effects.

Thankfully, the screening pathway is evolving. Now there are better ways to know what a high or rising PSA means before having a biopsy. In fact, an unnecessary biopsy can be avoided due to two breakthroughs.

The first breakthrough is an immediate multiparametric MRI (mpMRI) after a suspicious PSA. Unlike ultrasound, which does not tell the difference between healthy prostate and PCa, mpMRI provides a 3-D anatomic portrait of the prostate that distinguishes between healthy tissue and significant PCa. If a cancerous area is detected, a real-time MRI-guided biopsy can target a minimum number of needles directly into that area. This greatly increases biopsy accuracy while reducing biopsy risks.

The second breakthrough is the ability to identify biomarkers that are highly specific for PCa. Unlike PSA, which can mean several things, there are telltale substances that can be found in blood or urine that indicate the presence of PCa.

Can these breakthroughs show if a biopsy is needed?

Yes, that’s the whole point. A PSA test alone can’t tell if a biopsy is necessary, but MRI and biomarkers take the guesswork out. Even so, imaging and biomarkers are not a certain diagnosis.

The reason a biopsy is needed to establish the presence of PCa is to obtain actual cells that will be examined under a microscope. Not only does this definitely identify cancer, it allows the cancer to receive a Gleason grade or Grade Group indicating how dangerous it is. Once the location, size, and aggression level are known, a treatment can be tailored to the patient’s PCa.

To explain how the screening pathway has changed, PCa expert Dr. Stacy Loeb gave a presentation to the 2025 annual meeting of LUGPA (Large Urology Group Practice Association). Her key points:

• It is now recommended that all men have a baseline PSA between ages 40-50
• The age and PSA value should be risk-adapted, since some men have more risk factors for developing significant PCa than others
• The intervals between blood draws should take risk into account
• Guidelines encourage shared decision-making between doctor and patient
• MRI is the most transformative element in the screening pathway because it not only helps with risk stratification, it localizes the tumor which allows a better, targeted biopsy

No doubt, future technologies will improve the screening pathway even more. For now, the way in which mpMRI has influenced its evolution is a great benefit to PCa patients.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.