IsoPSA: One Step Closer to a Better Prostate Cancer Blood Test

“Build a better mousetrap, and the world will beat a path to your door.”
Ralph Waldo Emerson

The entire world of prostate cancer is eagerly waiting for a better prostate cancer (PCa) blood test. Before the development of the Prostate Specific Antigen (PSA) blood test, countless patients were diagnosed only after symptoms appeared, and by then their cancer had generally left the gland. This meant a high prostate cancer mortality rate.

When the PSA blood test was introduced in the mid-1990s as a way to screen for possible PCa, the death rate dropped dramatically over the following decade. However, that reduction came with a price. Most men who were found to have a high (or rising) PSA were promptly sent for an ultrasound-guided biopsy (TRUS biopsy). In turn, this often had one of two general outcomes:

  1. If the biopsy picked up PCa, they were quickly sent for surgery or radiation – even if they had a low risk Gleason score of 3+3.
  2. Or, the biopsy missed cancer altogether (a “false negative”), even if they had Gleason 3+4 or higher disease.

This led to a series of confusing and conflicting statements from the U.S. Preventive Services Task Force about broad PSA screening, since for untold thousands of men it was doing more harm than good.

Need for a better blood test

The core problem was the test itself. All prostate cells, whether they are cancerous or not, have surface proteins called antigens. While PSA has a role to play in liquefying semen, some of it also makes its way into the bloodstream. Prostate cells “shed” PSA into the blood when the gland is stimulated or disturbed in some way. This can occur not only during sexual activity and ejaculation, but also by things like prostate inflammation, BPH (benign gland enlargement with aging), infection, even riding a bike or the digital rectal exam. And of course, cancer activity in the prostate also disturbs the gland, so more PSA is released. This is how PSA came to be understood as possible evidence of prostate cancer.

Thus, PSA is a biomarker because its presence in the blood is a measure of prostate activity. Does this automatically mean a man has prostate cancer? No, it does not, and that’s the problem.

The new IsoPSA test

In 2017, a group of researchers from the Cleveland Clinic announced that they had developed a new molecular blood test that could tell the difference between prostate cancer and noncancerous conditions. It could even identify which patients had likely high-risk disease. This was based on a preliminary study conducted at five academic and community urology centers. An accurate blood test would mean that men with negative results would not need a biopsy! However, the preliminary results needed more confirmation.

A validation study was completed in time for the 2018 American Urological Association annual meeting in May. The news was just as good the second time around. The Cleveland team’s lead researcher, Dr. Eric Klein, commented on the results:

…IsoPSA has a 94% sensitivity for detecting high-grade (Gleason score 7 or higher) cancer and a 93% negative predictive value for high-grade cancer, Dr Klein said. ‘If you have a low IsoPSA number, you’re about 93% certain that you don’t have high-grade cancer,’ he said. Results showed that 47% of prostate biopsies could have been avoided.[i]

The patients in the study also had multiparametric MRI which, in the hands of an expert, is able to detect high-grade cancer before a biopsy. During the clinical study, the combination of IsoPSA and mpMRI proved 86% accurate in pre-biopsy identification of high risk PCa. Dr. Klein commented, “That’s pretty good, certainly much better than standard PSA and free PSA.”[ii]

What’s the difference in blood tests?

The difference between conventional PSA and the new IsoPSA test has to do with the 3-dimensional molecular form of the PSA protein molecules. A traditional PSA test is a simple count, whereas the IsoPSA can define the distinctive 3-D structure of PSA from the cancer cells. Essentially, this “unmasks” prostate cancer, making it identifiable by a blood test.

But a word of caution is in order: the IsoPSA test is NOT the equivalent of a prostate biopsy, which diagnoses the physical tumor itself. Thus, IsoPSA is very highly accurate in showing whether or not a biopsy is needed, but a doctor cannot make a treatment decision based on a positive IsoPSA result alone.

The best way to obtain that information is by real-time MRI-guided targeted biopsy. Since mpMRI reveals the size, shape, location, and clues to aggression, Dr. Sperling can direct a minimum number of needles into the core of the tumor where the most dangerous cells are likely to be found. Unlike the standard TRUS biopsy, there is nothing random or blind about Dr. Sperling’s biopsy method – and the fewer the needles, the lower the risks.

Without a doubt, until something better comes along, the prostate cancer world will beat a path to the IsoPSA once it’s FDA-approved.


[i] Charnow, Jodie. “Novel Blood Test Improves Detection of High-Grade Prostate Cancer.” Renal & Urology News, May 18, 2018.

[ii] Ibid.