Genetic Analysis Might Improve PSA Accuracy

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(ChemotherapyAdvisor) – Correcting serum prostate specific antigen (PSA) measurements using patients' genotype information significantly reduces the percentage of white men who meet commonly-employed prostate biopsy thresholds (PSA ≥2.5 or ≥4.0 ng/mL), report authors of a study published in The Journal of Urology.

Genetic correction of serum PSA levels “could lead to an 18-22% reduction in the number of potentially unnecessary biopsies and a 3% decrease in potentially delayed diagnoses,” wrote senior author William J. Catalona, MD, of the Department of Urology at the Feinberg School of Medicine, Northwestern University, Chicago, IL, and his coauthors.

“Although PSA is highly prostate-specific, it is not cancer-specific,” the authors noted. “For example, serum PSA levels may be increased with urinary tract infections, urinary tract instrumentation, and/or other benign conditions, including benign prostatic hyperplasia.”

It is not surprising, therefore, approximately 33% of men with PSA levels elevated above 10 ng/mL are found not to have prostate cancer after biopsy. The American Urological Association's best practice recommendations emphasize consideration of additional clinical data, such as PSA velocity, patient ethnicity and age, and family cancer histories.

“We hypothesized that genetic factors that are associated with increases or decreases in serum PSA concentrations may provide improved specificity for early detection and aid in determining whether a prostate biopsy is warranted,” the authors wrote.

To find out, the authors studied a cohort of 964 healthy Caucasian men during 2003-2009 (59 of whom underwent prostate biopsy), taking blood samples for genotype analysis and recording clinicopathological features, including serum PSA, family history of prostate cancer, and the number of prostate biopsies, they reported. Genetic analyses characterized four SNPs found within or near the PSA-encoding kallikrein-related peptidase 3 (KLK3) gene, found in previous studies to be “principally associated” with serum PSA concentrations, the authors wrote.

They found “an 18.3% reduction in the number of men who initially had a measured serum PSA above biopsy criteria (threshold) but fell below it after genetic correction (i.e., potentially unnecessary biopsies) and a 3.4% reduction in the number of men who had a measured PSA below biopsy criteria but went above it after genetic correction (i.e., potentially delayed biopsies).”

“If we limited our population to men with an unadjusted PSA ≥2.5 ng/mL, genetic correction could possibly prevent one of every 6 biopsies,” the authors concluded. “If confirmed, this approach could potentially be used to tailor PSA screening, possibly reducing unnecessary biopsies and avoid delay in performing necessary biopsies.”

Abstract

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