Fluctuation in prostate cancer gene 3 (PCA3) score in men undergoing first or repeat prostate biopsies.

ABSTRACT

OBJECTIVE: To evaluate the variability in prostate cancer gene 3 (PCA3) score over time in men with elevated serum prostate-specific antigen (PSA) levels who are undergoing first or repeat prostate biopsy. PATIENTS AND METHODS: A total of 360 men from two Italian institutions who had undergone at least two PCA3 assessments were selected. Of these, 97.5% were scheduled for first or repeat prostate biopsy because of elevated PSA level and/or positive digital rectal examination (DRE). We compared the PCA3 scores in men with a negative biopsy (normal parenchyma, benign prostatic hyperplasia [BPH], chronic prostatitis, high-grade prostate intraepithelial neoplasia [HG-PIN]) with those in men with a positive biopsy. We evaluated PCA3 repeated measures biological variability and its possible association with basic patient characteristics (age, family history of prostate cancer, DRE, prostate volume, BPH, prostatitis and HG-PIN). Three different thresholds were used to evaluate the possible changes in risk class the standard threshold (a PCA3 score of 35), a US Food and Drug Administation-approved PCA3 threshold of 25 and a threshold selected based on our previous research which was a PCA3 score of 50. RESULTS: The PCA3 scores varied significantly (P < 0.001) when comparing men with a negative biopsy with those with a positive biopsy (median [range] PCA3 score 25 [2-276] vs 43 [7-331]). There was no significant difference in PCA3 scores in men with chronic prostatitis and HG-PIN compared with other men with negative biopsies. The median (range) time between the two PCA3 assessments was 16.2 (3-53.7) months. No association was found between PCA3 repeated measures modifications and age, family history of prostate cancer, DRE, BPH, prostatitis, HG-PIN and use of 5-α-reductase inhibitors. The variability of PCA3 scores on repeated measures confirmed the risk class for about 80% of patients; of the remaining 20% of patients, the risk class was upgraded in two thirds and downgraded in one third. CONCLUSION: PCA3 score can be considered a stable marker over time in most cases but there is a group of men among whom there is clinically notable risk class change. Further investigation is required to determine the genesis of this phenomenon.