Personalized Prostate Cancer Screening Improves Specificity

Genetic variants have been identified that can increase serum prostate specific antigen (PSA) concentrations and prostate cancer risk. Correcting PSA levels for these genetic variants can have significant consequences, among them avoiding unnecessary biopsies for some men and eliminating false complacency for others.

Scientists at Northwestern University (Evanston, IL, USA) determined the genotypes of four single nucleotide polymorphisms previously associated with serum prostate specific antigen levels of 964 healthy Caucasian men. Genetic correction of prostate specific antigen was performed by dividing an individual's prostate specific antigen value by his combined genetic risk.

Correcting individual PSA levels for these genetic variants led to an 18.3% reduction in the number of men who initially had a measured serum PSA above the biopsy criteria, but whose adjusted PSA fell below the cutoff value. In this latter group, the men would have likely undergone what would have been an unnecessary biopsy. Conversely, genetic correction led to PSA levels moving from below threshold to above threshold for 3.4% of the men, consequently sending out a signal that these results need further investigation.

For 98% of the men, genetic adjustment of PSA levels did not change outcome. However, genetic correction was important for the 17 men who were reclassified as no longer meeting the biopsy criteria of a PSA of 2.5 ng/mL or greater and the three whose condition was reclassified up. The results suggest that traditional single cutoff PSA screening levels of 2.5 ng/mL or greater or 4.0 ng/mL or greater should be personalized to reflect an individual's genetic make-up.

William J. Catalona, MD, a professor of urology and lead author of the study said, “If our results are validated, adjustment for the four PSA single nucleotide polymorphisms (SNPs) could potentially prevent up to 15% to 20% of prostate biopsies. Since it has been estimated that more than one million biopsies are performed in the United States of America annually, this could translate into 150,000 to 200,000 potentially unnecessary biopsies every year.” In addition to cost savings, fewer biopsies mean fewer adverse outcomes, such as infection, sepsis, and hospitalization. The study was published in the May 2013 issue of the Journal of Urology.

Related Links:
Northwestern University