Performance of prostate cancer antigen 3 (PCA3) and prostate-specific antigen in Prescreened men: reproducibility and detection characteristics for prostate cancer patients with high PCA3 scores (≥ 100).

Abstract

Prostate cancer antigen 3 (PCA3) is considered to be prostate cancer (PCa) specific and highly overexpressed in cancer. Therefore a high PCA3 score should result in a high positive predictive value (PPV) and specificity for a positive biopsy. Our aim was to reevaluate, retest PCA3, and rebiopsy men with an initial PCA3 ≥ 100 and no PCa detected and compare the results with a random cohort of men with an initial PCA3<100. We invited men 63-75 yr of age with a PCA3 ≥100 for retesting and a control group with an initial PCA3 < 100 to participate in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam. Blood and urine sampling were used to determine prostate-specific antigen (PSA) and PCA3. Prostate biopsies were performed if the PSA was ≥2.5 ng/ml and/or the PCA3 score was ≥ 35. We correlated the initial and reevaluated PCA3 scores. Our assessment of the PPV after rebiopsy was based on the newly determined PCA3 score. After a mean study period of 19 mo, more cases of PCa were detected in rebiopsied men with initial PCA3 scores ≥ 100 than in the controls with PCA3 scores < 100 (30.0% vs 18.8%). Combining initial and rebiopsy data resulted in a PPV of 52.2% in men with PCA3 ≥ 100. Over time, changes in PSA and PCA3 levels were quite different. In spite of our rescreened population, PPV and specificity were comparable with all reported studies of men with PCA3 scores ≥ 100. These findings do not explain why these PCA3 scores were excessively high in spite of the absence of biopsy-detectable PCa.