Nick Mulcahy

May 23, 2014

ORLANDO, Florida — A newly available commercial blood test performs better than a commonly used online risk calculator in predicting which men with an elevated prostate-specific antigen (PSA) level will ultimately turn out, on biopsy, to have high-grade disease.

"This is a test that can personalize the risk of having a clinically relevant prostate cancer that deserves diagnosis," said lead author Daniel Lin, MD, from the University of Washington in Seattle, in an interview with Medscape Medical News.

He presented data on the blood test, known as the 4KScore test (OPKO Diagnostics), here at the American Urological Association (AUA) 2014 Annual Scientific Meeting.

4KScore is an assay panel that combines 3 PSA measures (total, free, and intact) with another prostate-specific measure, human kallikrein 2 (hK2), in an algorithm that takes into account a patient's age, digital rectal exam result, and previous biopsy status.

Dr. Lin and colleagues compared the 4KScore test with the Prostate Cancer Prevention Trial (PCPT) risk calculator in more than 1400 men. All had elevated PSA levels and were referred for biopsy at 26 centers in the United States from October 2013 to January 2014.

All of the men eventually underwent a 10-core biopsy.

The study population reflected "what would be seen in the community-practice population," said Dr. Lin.

About half of the biopsies (54%) were negative. Gleason score was 6 in 23% of the biopsies and was 7 or higher in 23%.

Before the biopsies were performed, the men had their blood analyzed at the 4KScore test laboratory in Nashville, Tennessee. Relevant data for each man were also entered into the PCPT online calculator, version 2.0.

For detecting high-grade disease, 4KScore had a "very robust and high" area under the curve (AUC), which compared favorably with the PCPT AUC (0.82 vs 0.74), Dr. Lin reported.

This finding could be considered the "take-home result" of the study, Dr. Lin told an AUA plenary session audience.

In other words, in the study population, 4KScore was incrementally better than PCPT at predicting — prebiopsy — the occurrence of high-grade disease on biopsy. The 4KScore test costs $395; PCPT is free.

The "widely used" PCPT was chosen for the study because it is the "best comparator" and uses clinical values to "ascertain high-risk prostate cancer," said Dr. Lin.

The 4KScore test did a very good job.

"The 4KScore test did a very good job at detecting high-grade cancer," said Stacy Loeb, MD, from New York University in New York City. She was not involved in the study and was asked to comment by Medscape Medical News.

However, Dr. Loeb said that another prebiopsy blood test, the Prostate Health Index (PHI), is "similarly effective in detecting high-risk prostate cancer." PHI is also considerably cheaper — at just $80, said Dr. Loeb, who has been a PHI investigator.

Detecting higher-grade disease (a Gleason score of at least 7) is crucial because treatment of intermediate- and high-risk disease is supported by clinical trials, and a survival benefit has been seen in these men, said Dr. Lin.

4KScore gives a "spectrum of risk" for high-grade cancer — from 1% to 95% — instead of providing a cutoff point like other tests do, he explained.

He showed a slide of a man who had a 9% chance of having a high-grade cancer on the basis of his 4KScore. This positive predictive value corresponds with a negative predictive value — in this case, 91%. The decision of whether to have a biopsy for this slight risk for high-grade disease would be based on patient preference, as well as factors such as comorbidities, Dr. Lin said.

The investigators also calculated the reduction in "unnecessary" biopsies as a result of the use of the 4KScore test in the study population. They found that biopsies would have been reduced by 30% to 58%, he reported.

Bold Statements

In retrospective studies of more than 7500 men that used data from the European Randomized Study of Screening for Prostate Cancer, the 4KScore test has been shown to reduce biopsies in screened and unscreened men by 27% to 82%, according to Dr. Lin.

He explained that his team undertook their study to replicate the European performance in an independent, prospective, blinded study, and to address possible differences in the 2 populations.

These new data are "more compelling" for clinicians in the United States, said Dr. Loeb.

During his presentation, Dr. Lin placed the test results in a larger context.

PSA screening leads to a lot of unnecessary biopsies, he said. Approximately 60% of initial biopsies are negative, and half of all positive biopsies are for low-grade prostate cancer (Gleason score of 6 or lower).

Because there is controversy surrounding the detection and treatment of low-grade prostate cancers, PSA screening is also controversial, he explained.

The 4KScore test could address much of the PSA screening controversy.

"The 4KScore test could address much of the PSA screening controversy," Dr. Lin stated. "If we biopsy the right men and do not detect indolent disease," he said, "then we more efficiently screen men."

Overdiagnosis of prostate cancer is the "main problem," according to critics of PSA screening, such as the US Preventive Services Task Force, added Dr. Lin.

The group famously recommended in 2012 that no healthy American men of any age undergo PSA testing because of a lack of favorable harm/benefit balance.

Funding for this study was provided by OPKO Diagnostics. Dr. Lin and Dr. Loeb have disclosed no relevant financial relationships.

American Urological Association (AUA) 2014 Annual Scientific Meeting: Abstract PI-06. Presented May 18, 2014.


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