Here’s a startling statistic: As many as 75% of PSA tests are false positives. That means a high test result was not due to prostate cancer. Instead, something else was driving up the number, such as BPH, some type of inflammation, or activity like riding a bike or having sex.
Not so long ago, the only way to find out if prostate cancer was the real culprit was a needle biopsy. Like the PSA test, a 12-needle TRUS-guided biopsy also has a margin of error. Men dreaded it due to potential risks such as pain and infection, not to mention the fear of actually diagnosing cancer.
If the biopsy found cancer, most men were sent for surgery or radiation. These whole-gland treatments likewise had potential risks that lessen quality of life—and could even be permanent.
In many cases, the low-risk cancer may not have required immediate treatment. Such cancers are called clinically insignificant. Nowadays, Active Surveillance for low-risk disease is a good monitoring strategy to hold off on whole-gland treatment. However, as recently as 10 years ago doctors wanted to take no chances that the biopsy needles had missed more aggressive cancer cells that are called clinically significant prostate cancer, so whole gland treatment was recommended. In fact, clinically significant disease should be removed or destroyed before it has a chance to spread.
For the first time in history, the PSA test gave an early clue that prostate cancer might be present. Since the majority of tests resulted in false positives, however, untold thousands of men had a biopsy for nothing. The problem was, there was no other way to pin down the meaning of a high PSA result.
Avoiding unnecessary biopsies
This situation created a clinical goal to avoid putting men through an invasive test unless there was clear necessity for it. Thankfully, a new approach has finally been developed to detect cancer clues before taking needle tissue samples. Such clues are called biomarkers, and they can be found in body fluids.
The National Cancer Institute defines a biomarker as a “biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.”
The PSA test itself measures a cell protein biomarker called prostate specific antigen (PSA). If the prostate gland is disturbed, it causes more PSA to enter the bloodstream. Thus, PSA is a biomarker for ANY prostate cell activity, not just prostate cancer. If a PSA test result is abnormally high, it raises two key questions that the test alone can’t answer:
- Does a high PSA result mean prostate cancer is the cause?
- If it’s prostate cancer, is it clinically significant?
Not being specific for prostate cancer, PSA is an imperfect biomarker. Something more specific is needed.
Comparing two biomarker tests
Scientists have been hard at work identifying biomarkers that are prostate cancer-specific. It’s a challenge, because prostate cancer cells originate from normal prostate cells, so they share many of the same molecular characteristics. This meant identifying genomic mutations of prostate cancer cells that normal prostate cells don’t have.
Recently, the Desai Sethi Urology Institute (U. of Miami) announced results of a comparison study of a urine-based biomarker and a blood-based biomarker to see which performed more accurately. According to a May 2026 news story, research team leader Dr. Sanoj Punnen presented the “MDSelect Trial” at AUA2026, the American Urologic Association’s annual meeting.
Here are the two biomarker tests that were compared:
- The ExoDx Prostate test, a urine liquid biomarker test that helps urologists identify patients who have a low versus high risk of clinically significant disease, independent of PSA testing and other standard of care parameters.
- The 4Kscore Test, a blood-based analysis of 4 biomarkers that improves the prediction of clinically significant prostate cancer before biopsy.
The role of multiparametric MRI (mpMRI)
In this study, the 4Kscore performed slightly better than the ExoDx based on biomarkers only, but the difference was not significant. However, when scan results from multiparametric MRI (mpMRI) were combined with either biomarker, their accuracy was comparable.
mpMRI of the prostate plays an essential role in determining if a biopsy is needed or not. Thanks to the ability of the PI-RADS score, mpMRI is used to stratify a patient’s risk level in order to determine if a biopsy is needed.
The Sperling Prostate Center is a top-tier facility for detecting clinically significant prostate cancer based on Dr. Sperling’s expertise in reading scans from our powerful 3 Tesla magnet. Biomarker analysis may be included if indicated.
Our Center is invested in sparing patients from a needle biopsy if there is no necessity. In addition, if a biopsy is needed, we offer in-bore MRI-guided targeted biopsy, which generally requires 2-4 needles, and has the highest diagnostic accuracy. Contact the Sperling Prostate Center for more information.
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.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
