News

NCCN recommends IsoPSA test for upfront prostate cancer risk assessment

 

 

SAP Partner | <b>Cleveland Clinic</b>
 

The IsoPSA test has been added to the National Comprehensive Cancer Network Prostate Cancer guidelines for early detection of the disease, according to Cleveland Diagnostics, the developer of the assay.1

The blood-based, non-invasive IsoPSA test is used prior to an initial biopsy to assess the likelihood that a patient has high-grade prostate cancer.

Eric Klein, MD

Eric Klein, MD

“IsoPSA is intended to be used in men over 50 who are being screened for prostate cancer as a way of helping to decide whether or not a biopsy should be done. So the standard paradigm is someone has a PSA test, and we know that PSA is only a little better than a coin flip in determining whether or not someone has prostate cancer. In our prior published studies, IsoPSA is far better than that. It has 80% accuracy or better in predicting for hi-grade cancer. And in fact, if it’s used in conjunction with MRI, we found that it was close to 85% accurate. So it’s far better than PSA in deciding whether or not someone might have a hi-grade cancer that deserves a biopsy,” Eric Klein, MD, fellow, Stanford University Distinguished Careers Institute and Emeritus Professor and Chair, Glickman Urological and Kidney Institute, Cleveland Clinic, said in an interview earlier this year with Urology Times.

Klein was the lead investigator on a real-world clinical validation study of IsoPSA that was published in the Journal of Urology Practice. The study included a diverse group of 38 community-based and academic sites withing the Cleveland Clinic health system. There were 900 patients under evaluation for prostate cancer who were enrolled at these locations. Of these, 734 met the study inclusion criteria, which comprised age ≥50 years, total serum PSA ≥4 ng/ml and <100 ng/ml, and no history of prostate cancer. The study investigators assessed biopsy recommendations of participating clinicians before and after receipt of IsoPSA results.

The results showed that in men with total PSA ≥4 ng/ml, IsoPSA led to a 55% (284 vs 638) net reduction in prostate biopsy recommendations. Further, there was also a 9% reduction in MRI imaging recommendations.

“What we found was really remarkable and it was what we had hoped for. The whole point of using IsoPSA is because it has improved sensitivity and specificity for finding higher grade cancers—grade seven or higher. The intended use of IsoPSA is to reduce the number of biopsies that show only benign tissue or show only low-grade cancer; those are things that we’d rather not find on labs,” said Klein.

“And what we found was that incorporating IsoPSA into practice for these 38 providers changed their recommendations about whether additional evaluation was necessary based on an initial total PSA; More than half—55%—of biopsies that otherwise would have been recommended, and probably would have happened, actually were recommended against. And so in this population of 900 patients, we saved a little more than half of them from the need for undergoing a biopsy with high confidence that we’re not overlooking a hi-grade cancer,” Klein added.

Regarding the next steps with IsoPSA, Klein said, “Going forward we have a paper pending on a multinational, multicenter trial of little over 1000 men that confirmed the prior performance characteristics of IsoPSA in terms of sensitivity and specificity of positive and negative predictive value and that sort of thing; that’s under review currently. And IsoPSA received FDA breakthrough technology designation about 2 years ago and so there is a pending FDA application for premarket approval.”

Reference

1. Scovell JM, Hettel D, Abouassaly R, et al. IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study. Journal of Urology Practice. 2022;9(2):173-180. doi: 10.1097/UPJ.0000000000000291

 
 

IsoPSA cuts biopsy rate in half for newbies

Wonderful world’ ahead in AS? Better anyway.

 

New PSA test may change the future of screening newbies as well as AS (Part II)

By Howard Wolinsky

IsoPSA.

You probably haven’t heard of it until now.

But at least, you’ll be familiar with the PSA part as men who have undergone screening for prostate cancer.

We follow our PSAs to determine whether to have a biopsy. As Active Surveillors, we have been diagnosed with low-risk PCa and are following PSAs of above 4.0 ng/mL to determine if we need an mpMRI and a focused biopsy to determine next steps.

IsoPSA may hold the key to a new future for men who up to now were put on Active Surveillance. We’ll get to IsoPSA, which already is available commercially from https://www.clevelanddx.com/, in a moment.

First, some biology.

You don’t have to be an A student as the late Sam Cooke crooned in 1960 in his hit “Wonderful World”: “Don’t know much biology/Don’t know much about a science book.” 

You don’t have to know a lot. Just a little.

Prostate-specific antigens (PSA) are glycoproteins [sugar proteins] detected in blood tests. We’ve had PSAs to screen for prostate cancer and then, if the reading is above 4.0 ng/mL, we have PSAs to monitor our cancers and help determine if we need definitive treatment such as radical prostatectomy or radiation. 

Depending on the source, as many at least one million American men undergo biopsies based on their PSA scores. Maybe half of those biopsies are unnecessary, wasting an estimated $4 billion in health funding per year. 

Typically, these are transrectal biopsies that put men at risk of potentially deadly sepsis and other infections.

PSA is not cancer-specific since an enlarged prostate (benign prostatic hyperplasia) also can produce PSA. In fact, BPH is the leading cause of high PSAs.

Now back to IsoPSA and urologic oncologist Eric Klein, MD, emeritus chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. 

 

(Eric Klein, MD.)

(Note: Klein is currently on sabbatical and is an unpaid consultant faculty member at Cleveland Clinic and is a consultant to Cleveland Diagnostics. The Cleveland Clinic owns an equity stake in Cleveland Diagnostics. )

Don’t know chemistry?

Klein said: “PSA exists in multiple different forms, multiple different proteins in the blood that are called isoforms. An isoform is a slight variation in the structure of a protein.”

Fun fact:  BPH makes a slightly different form of PSA than cancer does. 

“If you have the right tools you can sort that out,” said Klein. “PSA exists in two general forms in the blood: free-floating PSA (called free PSA) and PSA that is bound to other blood proteins (called bound PSA).” 

There’s basic total PSA, which most of us have tested with a regular PSA assay quarterly or annually.

But there also are the phi (Prostate Health Index from Beckman Coulter Inc.), which combines free and bound forms of PSA plus an isoform known as pre-pro precursor (PreProPSA)

to produce a phi score, and the 4kscore Test (OPKO), which looks at total, free and intact forms plus the isoform human kallikrein 2 [hK2].

4Kscore and phi are used after a man has an abnormal reading above 4 before the patient has undergone a biopsy to help determine the risk of cancer being present and to help decide if a biopsy is indicated because of that risk.

“When you put them in the algorithm they can improve the ability to say this elevation in a concentration of PSA is more likely due to BPH or due to cancer. And they do that well. They are better than PSA alone,” Klein said.

While IsoPSA, which has been studied since 2011, is now used as a reflex test to help decide on who should have a biopsy, studies evaluating the utility of isoPSA for active surveillance are in the planning stages, he said, emphasizing that currently there is no established role for isoPSA in men on surveillance.  

More than concentrations in the blood

Regular PSAs, phi and 4kscore tests measure the concentration of PSA in the blood. 

IsoForm is more dynamic. The test measures all the isoforms–dozens, maybe hundreds– in the blood, increasing its accuracy. Unlike standard PSA tests, which assess the blood concentration of this protein, the IsoPSA test detects cancer by identifying cancer-related structural changes in PSA.

Klein said the net effect of how the isoforms interact with the solvent in the isoPSA test kit is what matters: separating isoforms of PSA based on protein structure and other physicochemical properties prior to determining the concentration of PSA structural variants using traditional immunoassay techniques.

Change for the better?

OK, we’re coming up to the good part for patients.

In studies of tissue of men about to undergo biopsies, IsoPSA outperformed regular PSA.

IsoPSA reduced the biopsy rate by 55% and eliminated the need for mpMRIs by 9% in a study at the Glickman Urological and Kidney Institute that involved test ordering and recommendations by general urologists, fellowship-trained urologic oncologists, and advanced practice providers. 

Brian Helfand, MD, PhD, head of NorthShore University HealthSystem in suburban Chicago, who uses the phi test, said, the tests “have not gone head-to-head. They claim (IsoPSA) is different, but don’t have the comparisons. In addition, they have not published (to my knowledge) how it performs in men on AS.”

Klein responded: “Let me be very clear. We have not tested IsoPSA in men on Active Surveillance. We have not. This is used as a reflex test for men who are not diagnosed with cancer where we’re trying to figure out whether or not we should do a biopsy.”

What’s a reflex test? Klein explained that refers to the reflex of the urologist of what to do when a patient’s PSA is between four and 10. “And I have a question in my head about whether that represents BPH or prostate cancer, so my reflex currently is to do a biopsy. A few years ago, we changed to do these other blood tests to see if we can refine our prediction of the likelihood of having cancer. Now, isoPSA, 4Kscore and phi all do that.

The main advantage that IsoPSA may bring to the active surveillance space is to substantially decrease the number of biopsies that show only low-grade cancer – fewer men with this result would mean fewer men having to go on active surveillance, with its attendant worry and need for repeated MRI and biopsies.”

Another issue

This brings up another issue. Patients–and maybe some doctors– find the results from 4Kscore and phi difficult to read.

Klein said, “The challenge with them is that they are hard to interpret. Have you ever seen the lab reports for either of those?” My answer is yes and yes.

 As one of Helfand’s patients, my eyes defocus when I read my phi results. I look for a bottom line reading such as “no change.”

Klein said IsoPSA reports are patient-friendly. Patients look at whether they are above or below a threshold. It looks like a pregnancy test.

FDA Grants Breakthrough Device Designation to IsoPSA Blood Test for PC  Diagnosis

New PSA test may change the future of screening newbies as well as AS (Part II)

By Howard Wolinsky

IsoPSA.

You probably haven’t heard of it until now.

But at least, you’ll be familiar with the PSA part as men who have undergone screening for prostate cancer, which entails following their PSAs to determine whether to have a biopsy or who, as an Active Surveillor, have been diagnosed with low-risk PCa and is following PSAs of above 4.0 ng/mL to determine if you need to move over to treatment after a mpMRI and a focused biopsy.

IsoPSA may hold the key to a new future for men who up to now were put on Active Surveillance. We’ll get to IsoPSA, which already is available commercially from

https://www.clevelanddx.com/

, in a moment.

First, some biology.

You don’t have to be an A student as the late Sam Cooke crooned in 1960 in his hit “Wonderful World”: “Don’t know much biology/Don’t know much about a science book.” 

You don’t have to know a lot. Just a little.

Prostate-specific antigens (PSA) are glycoproteins [sugar proteins] detected in blood tests. We’ve had PSAs to screen for prostate cancer and then, if  the reading is above 4.0 ng/mL, we have PSAs to monitor our cancers and help determine if we need definitive treatment such as radical prostatectomy or radiation. 

Depending on the source, as many at least one million American men undergo biopsies based on their PSA scores. Maybe half of those biopsies are unnecessary, wasting an estimated $4 billion in health funding per year. 

Typically, these are transrectal biopsies that put men at risk of potentially deadly sepsis and other infections.

PSA is not cancer-specific since an enlarged prostate (benign prostatic hyperplasia) also can produce PSA. In fact, BPH is the leading cause of high PSAs.

Now back to IsoPSA and urologic oncologist Eric Klein, MD, emeritus chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. 

(Note: Klein is currently on sabbatical and is an unpaid consultant faculty member at Cleveland Clinic and is a consultant to Cleveland Diagnostics. The Cleveland Clinic owns an equity stake in Cleveland Diagnostics. )

Don’t know chemistry?

Klein said: “PSA exists in multiple different forms, multiple different proteins in the blood that are called isoforms. An isoform is a slight variation in the structure of a protein.”

Fun fact:  BPH makes a slightly different form of PSA than cancer does. 

“If you have the right tools you can sort that out,” said Klein. “PSA exists in two general forms in the blood: free-floating PSA (called free PSA) and PSA that is bound to other blood proteins (called bound PSA).” 

There’s basic total PSA, which most of us have tested with a regular PSA assay quarterly or annually.

But there also are the phi (Prostate Health Index from Beckman Coulter Inc.), which combines free and bound forms of PSA plus an isoform known as pre-pro precursor (PreProPSA)

to produce a phi score, and the 4kscore Test (OPKO), which looks at total, free and intact forms plus the isoform human kallikrein 2 [hK2].

4Kscore and phi are used after a man has an abnormal reading above 4 before the patient has undergone a biopsy to help determine the risk of cancer being present and to help decide if a biopsy is indicated because of that risk.

“When you put them in the algorithm they can improve the ability to say this elevation in a concentration of PSA is more likely due to BPH or due to cancer. And they do that well. They are better than PSA alone,” Klein said.

While IsoPSA, which has been studied since 2011, is now used as a reflex test to help decide on who should have a biopsy, studies evaluating the utility of isoPSA for active surveillance are in the planning stages, he said, emphasizing that currently there is no established role for isoPSA in men on surveillance.  

More than concentrations in the blood

Regular PSAs, phi and 4kscore tests measure the concentration of PSA in the blood. 

IsoForm is more dynamic. The test measures all the isoforms–dozens, maybe hundreds– in the blood, increasing its accuracy.

Klein said the net effect of how the isoforms interact with the solvent in the isoPSA test kit is what matters: separating isoforms of PSA based on protein structure and other physicochemical properties prior to determining the concentration of PSA structural variants using traditional immunoassay techniques.

Change for the better?

OK, we’re coming up to the good part for patients.

In studies of tissue of men about to undergo biopsies, IsoPSA outperformed regular PSA.

IsoPSA reduced the biopsy rate by 55% and eliminated the need for mpMRIs by 9% in a study at the Glickman Urological and Kidney Institute that involved test ordering and recommendations by general urologists, fellowship-trained urologic oncologists, and advanced practice providers. 

Brian Helfand, MD, PhD, head of NorthShore University HealthSystem in suburban Chicago, who uses the phi test, said, the tests “have not gone head-to-head. They claim (IsoPSA) is different, but don’t have the comparisons. In addition, they have not published (to my knowledge) how it performs in men on AS.”

Klein responded: “Let me be very clear. We have not tested IsoPSA in men on Active Surveillance. We have not. This is used as a reflex test for men who are not diagnosed with cancer where we’re trying to figure out whether or not we should do a biopsy.”

What’s a reflex test? Klein explained that refers to the reflex of the urologist of what to do when a patient’s PSA is between four and 10. “And I have a question in my head about whether that represents BPH or prostate cancer, so my reflex currently is to do a biopsy. A few years ago, we changed to do these other blood tests to see if we can refine our prediction of the likelihood of having cancer. Now, isoPSA, 4Kscore and phi all do that.

The main advantage that IsoPSA may bring to the active surveillance space is to substantially decrease the number of biopsies that show only low-grade cancer – fewer men with this result would mean fewer men having to go on active surveillance, with its attendant worry and need for repeated MRI and biopsies.”

Another issue

This brings up another issue. Patients–and maybe some doctors– find the results from 4Kscore and phi difficult to read.

Klein said, “The challenge with them is that they are hard to interpret. Have you ever seen the lab reports for either of those?” My answer is yes and yes.

 As one of Helfand’s patients, my eyes defocus when I read my phi results. I look for a bottom-line reading such as “no change.”

Klein said IsoPSA reports are patient-friendly. Patients look at whether they are above or below a threshold. 

Todd Morgan, MD, chief of urologic oncology at the University of Michigan, said of IsoPSA: “The data look encouraging and this may well have clinical use in the future. They’ve done a great job developing this assay, and it could help with the identification of which men with an elevated PSA should undergo additional testing with an MRI and/or biopsy. 

“The big challenge is that we now have an incredible wealth of prostate cancer biomarkers for early detection and very little comparative data. At the end of the day, the field would be well served by some clarity from comparative studies that help identify the best performing tests in a given patient population.”

Doctors and patients need those kinds of comparisons to make informed decisions.

Klein said the plan is to study IsoPSA in men on AS in the near future.

IsoPSA is available as a pre-biopsy blood test from Cleveland Diagnostics for about $400. Under the rules from the Food and Drug Administration, IsoPSA is considered a laboratory-developed test (LDT), a type of in vitro diagnostic test designed, manufactured and used within a single laboratory. FDA designated IsoPSA as an LDT in 2019.

However, Klein is hopeful for  two big things by year’s end: 

(1) The FDA will approve IsoPSA as a diagnostic, which will make it available far more easily and widely. 

(2) The National Comprehensive Cancer Center Network (NCCN) will incorporate IsoPSA into its guidelines.

These changes would be huge deals for those few men who have PSAs in the reflex zone of 4-10.  It could spare many men from being diagnosed with low-grade cancers and the ritual and rigamarole of AS: regular MRIs, biopsies, digital rectal exams, and urologist visits.

Also, planning is in place to determine if IsoPSA could serve as a replacement for regular PSAs as a more accurate approach for screening the undiagnosed and those of us who already are on active surveillance.

This could represent a game-changer for the AS world. 

As Cooke said: “What a wonderful world this would be.”

Todd Morgan, MD, chief of urologic oncology at the University of Michigan, said of IsoPSA: “The data look encouraging and this may well have clinical use in the future. They’ve done a great job developing this assay, and it could help with the identification of which men with an elevated PSA should undergo additional testing with an MRI and/or biopsy. 

“The big challenge is that we now have an incredible wealth of prostate cancer biomarkers for early detection and very little comparative data. At the end of the day, the field would be well served by some clarity from comparative studies that help identify the best performing tests in a given patient population.”

Doctors and patients need those kinds of comparisons to make informed decisions.

Klein said the plan is to study IsoPSA in men on AS in the near future.

IsoPSA is available as a pre-biopsy blood test from Cleveland Diagnostics for about $400. Under the rules from the Food and Drug Administration, IsoPSA is considered a laboratory-developed test (LDT), a type of in vitro diagnostic test designed, manufactured and used within a single laboratory.

However, Klein is hopeful for  two big things by year’s end: 

(1) The FDA will approve IsoPSA as a diagnostic, which will make it available far more easily and widely. 

(2) The National Comprehensive Cancer Center Network (NCCN) will incorporate IsoPSA into its guidelines.

These changes would be huge deals for those few men who have PSAs in the reflex zone of 4-10.  It could spare many men from being diagnosed with low-grade cancers and the ritual and rigamarole of AS: regular MRIs, biopsies, digital rectal exams, and urologist visits.

Also, planning is in place to determine if IsoPSA could serve as a replacement for regular PSAs as a more accurate approach for screening the undiagnosed and those of us who already are on active surveillance.

This could represent a game-changer for the AS world. 

As Cooke said: “What a wonderful world this would be.”


Talking about what the future holds for Active Surveillance, don’t miss this program: Top docs—including Dr. Laurence Klotz, who named AS; Dr. Peter Carroll and Dr. Peter Albertsen, who helped develop the approach, and Dr. E. David Crawford, who believes it’s time to move beyond AS— will be exploring the future of Active Surveillance at 11 a.m. Eastern April 22. Register here ASAP: https://zoom.us/meeting/register/tJEtfuuqrzwtHNPuqzkigx65YBk8vV-teUdy

Translate »