More information on the Prostate Health Index (phi)

I did a quick search on our HW site and found a few threads about the Prostate Health Index (phi), so I know it's been covered somewhat out here.  I recently came across a study that will be reporting on PHI compared to total PSA and %fPSA. First a general overview on PHI I found from a mid-2012 article: "Beckman Coulter, Inc, leader in prostate cancer diagnostics has announced the Premarket Approval from the U.S. Food and Drug Administration (FDA) on the new Prostate Health Index (phi) blood test. The new approved PHI test is 2.5x’s more specific in detecting prostate cancer than the controversial PSA test. It has shown a 31 percent reduction in unnecessary biopsies, and finally provides a new solution and screening tool for men and their physicians. There has been a mix of confusion and heated arguments over the effectiveness of the well known prostate specific antigen (PSA) test since the United States Preventative Services Task Force (USPSTF) openly gave it a “D” rating. USPSTF stated that the PSA test led to several unnecessary biopsies and ultimately called for “a better test and better treatment options.” U.S. physicians previously recommended that men with a PSA in the range of 4-10ng/mL consider having a prostate biopsy. However, studies further showed that an elevated PSA was because of benign conditions, and not cancer which would lead men to have an unnecessary biopsy. The Prostate Health Index test helps physicians distinguish prostate cancer from these benign conditions. The PHI test has been available in Europe for nearly 2 years for men with a PSA in the range of 2-10ng/mL, and is now finally available to men in the U.S who are in the 4-10ng/mL range. The benefit of this test is that it provides men with another option to screening methods, lowers health care cost, reduces the number of unnecessary biopsies, and prevents over diagnosis and treatments. Men with a PSA test result in the range of 4-10ng/mL now have the option to a new non-invasive treatment option that also proves more effective in the detection of prostate cancer." Also, a study was recently completed titled "Prostate Health Index (phi) for reducing overdetection of indolent prostate cancer and unnecessary biopsy while improving detection of aggressive cancers."  The full results of this study will be given as part of this year's annual AUA meeting next week, but I found the following summary:   Prostate Cancer: Detection & Screening (IV) Moderated Poster :showABS(2055);"> Prostate Health Index (phi) for reducing overdetection of indolent prostate cancer and unnecessary biopsy while improving detection of aggressive cancers Martin Sanda; John Wei; Dennis Broyles; Sanhuk Shin; Alan Partin; George Klee; Chris Bangma; Kevin Slawin; Leonard Marks; Amabelle Cruz; Isaac Mizrahi; Dan Chan; Lori Sokoll; Ron H.N. van Schaik; Stacy Loeb; William Catalona Abstract: 2055 Introduction and Objectives The Prostate Health Index (phi) was recently approved by the FDA for evaluating probability of prostate cancer (PCa) diagnosis, but its role in discerning aggressive versus indolent cancer, and thereby reducing over-diagnosis and unnecessary biopsy, has not been fully characterized. We investigated whether use of phi (as compared to total PSA and % fPSA) can reduce unnecessary biopsy and over-detection of indolent PCa while improving the detection of histo-pathologically aggressive PCa. Methods 658 men met inclusion criteria for analysis of clinically significant PCa as an endpoint in a multi-center prospective clinical trial. All men had a biopsy confirmed diagnosis, a final PSA between 4-10 ng/mL, were 50 years or older and had a benign rectal examination (DRE). We evaluated prediction of clinically significant cancer (aggressive histopathology per Epstein criteria or Gleason 7+) based on pre-biopsy measures of [-2]proPSA, total PSA, fPSA, %fPSA and phi. We evaluated prospects for eliminating unnecessary biopsy based on results of phi prior to biopsy. Results At 90% sensitivity the specificity of phi was 31.1%, compared to 19.8% for %fPSA (p = 0.024) and 10.8% for PSA (p < 0.001). At phi from 27 to 55 the probability of cancer ranged from 9.8 to 50.1%, and of clinically significant cancer from 3.9% to 28.9. Increasing phi values were associated with higher biopsy Gleason score (GS) (p trend < 0.01), and significant cancer based on Epstein criteria (p = 0.009). Among men with pre-biopsy phi < 27, the number of aggressive or significant cancers in our study was consistently very low based on either the Epstein criteria (11/137, 8.0%), GS > 3+4 (4/137, 2.9%), or GS > 4+3 (1/137, 0.7%). Only 1 of 35 (2.9%) cancers having GS 4+3 or worse had a phi < 27. At the 90% sensitivity cut-point for phi (phi=27), 120/639 (18.8%) men (104 biopsy negative for cancer and 16 with clinically insignificant cancer) could have been spared from undergoing prostate biopsy or over-diagnosis of non-aggressive disease. Conclusions phi outperformed PSA and %fPSA in predicting the presence of clinically significant PCa and for improving PCa detection. Using phi=27 for selecting men for PCa biopsy when total PSA is 4 to 10 ng/mL, can mitigate unnecessary biopsies and reduce over-detection of indolent PCa. Date & Time: May 8, 2013 08:00 AM Session Title: Prostate Cancer: Detection & Screening (IV) Sources of Funding: NIH U01 113913 (Sanda PI)_x000D_ Beckman Coulter My caveat to this is I do not yet have an opinion on phi nor am I trying to promote this - I simply found this as I was continuing my own education on PCa and thought I'd throw it out here for everyone's consideration.

Hi Allen, the only thing I found a fair amount about was for pre-market approval:

"FDA OKs New Prostate Cancer Blood Test

By John Gever, Senior Editor, MedPage Today
Published: June 26, 2012

 

A blood test for prostate cancer billed by its manufacturer as "an answer to the current PSA [prostate-specific antigen] testing controversy" has won FDA approval, the company said.
 
Beckman Coulter said Monday that the agency had okayed its premarket approval application for the so-called Prostate Health Index test, which incorporates measurement of a PSA precursor protein called [-2] pro-PSA along with total and free PSA."

 

To clear the air a bit on what FDA "Pre-Market Approval" means I found this on the FDA website:

"Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of class III devices. Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. Please note that some Class III preamendment devices may require a Class III 510(k).

 

FDA regulations provide 180 days to review the PMA and make a determination. In reality, the review time is normally longer. Before approving or denying a PMA, the appropriate FDA advisory committee may review the PMA at a public meeting and provide FDA with the committee's recommendation on whether FDA should approve the submission. After FDA notifies the applicant that the PMA has been approved or denied, a notice is published on the Internet (1) announcing the data on which the decision is based, and (2) providing interested persons an opportunity to petition FDA within 30 days for reconsideration of the decision."

I have not yet seen a ruling or notification from the FDA on this PMA.

Hi Tall Allen: nice to see you on this board. I sent an email to them in Feb, please see the answer below.


Your Original Message sent on Feb 27, 2013
Subject: Application/technical specification information - Immunoassay
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When will the Prostate Health Index test be available in California? Where will it be available, Quest Diagnostics?


Beckman Coulter?s Reply:
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The p2PSA/PHI assay will be available in the US sometime in 2013. It is currently not available at any site, including Quest, in the US. Best Regards, Lisa Dickey Advanced Specialist Customer Technical Support Beckman Coulter Inc. 800-854-3633


Thank you,

Beckman Coulter, Inc.
www.beckmancoulter.com

So, no firm date yet. Since I am on AS, it is of particular interest to me.

Guys, I can also tell you getting ANYTHING through FDA approval is incredibly difficult and time consuming. I'm the business unit manager of the medical devices division for a company in suburban Chicago, we manufacture medical devices, mainly implants and delivery systems for a customer base that includes OEM's like Medtronic, Abbott, BSCI, etc - so I know firsthand what could be involved in getting full US approval. While I can't speak to the drug market or tests such as the PHI, in our world of implants it's typically a 5 to 7 year cycle from design to approval.

This sure sounds like a promising tool, I hope they continue to move this forward.

Contact Beckman-Coulter in Europe.