The potential role for IsoPSA in prostate cancer risk assessment

In this interview, Jason M. Hafron, MD, discusses how IsoPSA, a blood test for the assessment of risk for high-grade prostate cancer, fits into the current diagnostic and treatment landscape. Hafron also highlights key findings from the study, “Using IsoPSA With Prostate Imaging Reporting and Data System Score May Help Refine Biopsy Decision Making in Patients With Elevated PSA.”¹

Jason M. Hafron, MD

Hafron is the chief medical officer and medical director of clinical research at the Michigan Institute of Urology, PC, as well as a professor of urology at the William Beaumont School of Medicine at Oakland University.

Could you discuss what IsoPSA is and how it is used in practice?

IsoPSA is a blood test that's indicated for men over 50 years old with a PSA greater than 4 ng/mL. It's meant to be an adjuvant marker for an abnormal PSA. IsoPSA does not simply measure PSA concentration, but it's looking at different isoforms of PSA. Using a 2-stage aqueous solution, it separates these isoforms and has a proprietary calculation to predict the likelihood of Gleason 7 and higher prostate cancer. When you look at the performance of IsoPSA in validation trials, you see that it outperforms standard PSA as well as free PSA in its accuracy and predictability in predicting high-grade prostate cancer. In our practice, we found IsoPSA to be very helpful. It's a simple blood test that we can order, and that can help guide on how we evaluate these patients with a PSA higher than 4 ng/mL.

Could you describe the background/key findings from the study, “Using IsoPSA With Prostate Imaging Reporting and Data System Score May Help Refine Biopsy Decision Making in Patients With Elevated PSA”?¹

I think it was an interesting trial because it gave us real practical numbers that we can use in everyday practice on how to integrate IsoPSA with MRI. Frequently we are faced with an MRI that has a PI-RADS 1, 2, or 3, but the patient has a rising PSA or there is suspicion that that PI-RADS 3 lesion might be significant. Historically, we've known that it may or may not be significant and it's vague on how to manage the PI-RADS 3 lesions.

What this study looked at–and it was a single center Cleveland Clinic dataset that they looked at with over 200 men–is that when you apply IsoPSA or integrate it into your MRI strategy, you can actually improve the performance of both the IsoPSA, as well as the MRI. So, getting back to that patient with the PI-RADS 3 lesion, if they have an IsoPSA less than 6 and a PI-RADS 3 lesion, the chance of that patient having clinically significant prostate cancer is less than 4%. If they have an abnormal IsoPSA greater than 6, that can go up to 16%. So, that's very helpful.

Also, it's very helpful in the patient with a PI-RADS 1 or 2. If they have a IsoPSA less than 6 or a normal IsoPSA, their risk of prostate cancer is 2%. So, that's a pretty strong note to leave those patients alone. If they have an abnormal IsoPSA, that percentage goes up to about 8%, but that's a discussion you can have with your patient.

The key from this paper is that now we have some good numbers to discuss with patients to decide on what's the best path forward, whether we need to biopsy or not. I think it's also very fair–and it's in the discussion and the conclusions of the paper–and every case is different, but if you have a PI-RADS 4 or 5, those patients probably should be biopsied regardless of the IsoPSA result. Again, the importance of this paper to clinical practice is that it gives us real numbers on what the likelihood is of cancer in those patients with PI-RADS 3 or less.

Could you elaborate on how IsoPSA may fit into the prostate cancer treatment landscape?

I think IsoPSA fits very well. We've had the good fortune of using IsoPSA for many years and have found it very helpful in our everyday practice. It's a simple blood test that can be sent out very easily. Eventually, the test may be FDA approved, so we may be able to offer it in our labs, making patient care even more coordinated.

Overall, IsoPSA really helps us decide who needs a biopsy and who doesn't need a biopsy. Looking at data, if you apply IsoPSA in a consistent manner, based on the studies published, you'll see up to a 55% reduction in unnecessary biopsies. The negative predictive value of IsoPSA is very strong, so you can decide pretty confidently who doesn't need a biopsy. The other aspect of it is, aside from being in the NCCN guidelines as a recommendation, that it's a very simple and straightforward test. it's above 6, it tells you that patient is at increased risk. There's even data coming out now that if it’s significantly higher than 6, the patient is at even higher increased risk. I think that the beauty of IsoPSA is that it's a simple blood test that has a very straightforward report that gives you the necessary information to decide who needs to be biopsied and who doesn't.

Are there any next steps with IsoPSA that you find particularly exciting?

I think IsoPSA is just at the tip of the iceberg. There's a lot more studies to be done with it. Some of the unique aspects of IsoPSA that have already been published is that it can work with 5-alpha reductase inhibitors; it's been validated with these drugs. But also, I think there’s more work to be done in African American populations to validate it a little bit better in those patient populations.

What’s also exciting is can IsoPSA, knowing that it can predict Gleason 7 or higher disease, can that be used in an active surveillance population? Can we use this as a marker to decide how often or how intensely we want to follow these patients? If they have a low IsoPSA, or an IsoPSA between 6 and 10, do we need to follow them as closely as a patient who has an IsoPSA of 15? I think there's a good opportunity to expand the uses–it's currently not approved for this–but to expand the use of IsoPSA to determine intensity of follow-up in the active surveillance population.

Reference

1. Benidir T, Lone Z, Wood A, et al. Using IsoPSA with Prostate Imaging Reporting and Data System Score may help refine biopsy decision making in patients with elevated PSA. Urology. 2023:176:115-120. doi:10.1016/j.urology.2023.03.014