Beyond PSA: New Prostate Cancer Screening Options

Ingrid Hein

August 07, 2020

In the wake of more than a decade of controversy over PSA testing, research is emerging that points to new approaches for the stratification of prostate cancer risk.

Two noninvasive tests — an assessment of spermine levels in urine and a blood test that combines free and total PSA and the (-2) pro-PSA isoform (p2PSA) — are much safer than historically risky biopsy and what is now considered to have been unnecessary surgery.

"We've 'cured' a lot of men," Franklin Gaylis, MD, from the University of California, San Diego, told Medscape Medical News. "Even some who didn't need to be cured." Now we are working to solve this dilemma, he said. "It's time we determine who do you screen, [who do you] not screen, and how aggressively?"

Urine Spermine Test More Accurate Than PSA

Data from a highly predictive test that assesses spermine levels in urine were presented by Peter Ka-Fung Chiu, MD, from the University of Hong Kong, at the virtual European Association of Urology (EAU) 2020 Congress. Normal spermine levels are inversely associated with both prostate cancer (PCa) and high-grade prostate cancer (HGPCa).

To investigate the predictive value of spermine for any PCa or HGPCa (Gleason 7 or above), the researchers recruited 556 men from two centers and collected 30 mL of urine prior to prostate biopsy.

They analyzed data from 390 men, and used decision-curve analyses for PCa and for HGPCa. The multivariate spermine score — which takes into account age, prostate volume, PSA level, and spermine level — provided net clinical benefit over PSA alone and over spermine score alone.

"At 90% sensitivity, this risk score actually had a negative predictive value of 96.7% and avoided about 50% of unnecessary biopsies," Chiu explained. "This test predicts prostate cancer and high-grade prostate cancer well, without the need for prior prostate massage, offering improved predictive performance."

PHI Reduces Need for MRI Screening

Another test, the PHI prostate cancer biomarker, is as predictive as multiparametric (mp)MRI, both with and without PSA scoring.

PHI scores from 554 men from five centers added to either PSA density or mpMRI improved the prediction of risk for ≥GG2 cancers to more than 0.81 and for ≥CPG3 cancers to more than 0.85, according to data from the multicenter PRIM (PHI to Refine MRI) study group recently published in BMC Medicine and presented at EAU.

With a PHI cut-off of 30, mpMRI referrals could be cut by 25%, and unnecessary biopsies could be cut by 40%, the PRIM group reports. PHI misses 8% of ≥GG2 cancers, whereas mpMRI misses 9%.

The PHI strategy reduces "mpMRI and biopsies without compromising detection of significant prostate cancers," and also reduces costs, Nicholas Boxall, MB ChB, from Cambridge University Hospitals NHS Foundation Trust in the United Kingdom, explained during his presentation

"Instead of screening everyone, we're risk-adapting who needs to be screened, identifying the right population and defaulting to MRI as an alternative to invasive biopsy, and doing secondary tests to look at biomarkers," said Gerald Andriole, MD, from the Washington University School of Medicine in St. Louis, Missouri.

"We don't have to auto-toggle to aggressive treatment," he told Medscape Medical News. "We're getting better than we were 10 years ago, but we need slightly better tests, and we also need better biopsies; urologists must be more careful."

Chiu and Boxall report no relevant financial relationships. Gaylis is a scientific advisor for Stratify Genomics. Andriole is on the advisory board of Stratify Genomics.

European Association of Urology (EAU) 2020 Congress: Abstracts 306 and 303. Presented July 17, 2020.

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