Abstract
Purpose: Prostate specific antigen tests have low specificity, which frequently results in unnecessary biopsy and typically limits screening to patients with prostate specific antigen greater than 4.0 ng/ml. We evaluated an investigational prostate cancer methylation specific polymerase chain reaction assay that detects aberrant methylation in 3 markers (GSTP1, RARβ2 and APC) that indicate the presence of prostate cancer. Materials and Methods: The assay was evaluated in 337 post-digital rectal examination urine samples (178 cancer and 159 noncancer) collected prospectively at a total of 9 clinical sites. Samples were processed wholly or after division into equal portions. Subject prostate specific antigen was 2.0 to 10.0 ng/ml. All subjects underwent transrectal ultrasound guided needle biopsy with 6 or greater cores sampled. Detection of 1 or greater markers indicated positivity. Results: Methylation specific polymerase chain reaction assay performance was better in whole than in divided urine cohorts (p = 0.035). Assay AUC was 0.72 in the whole urine cohort and 0.67 in the combined population. These values were higher than those of prostate specific antigen alone using 4.0 ng/ml as the cutoff (p = 0.00 and 0.01, respectively). Moreover, the assay together with the Prostate Cancer Prevention Trial risk calculator or a standard nomogram significantly improved AUC in the whole urine cohort and the combined population vs predictive algorithms alone (p <0.05). Assay positive predictive value was 54% in whole urine cohort with prostate specific antigen 2.0 to 4.0 ng/ml and negative predictive value was 87% with prostate specific antigen 4.1 to 10.0 ng/ml. Assay positive predictive value was higher in subjects with all 3 methylation markers positive. Conclusions: These data demonstrate that this investigational assay used in conjunction with current screening algorithms may potentially add value to the biopsy decision making process.
Original language | English (US) |
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Pages (from-to) | 1186-1193 |
Number of pages | 8 |
Journal | Journal of Urology |
Volume | 182 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2009 |
Keywords
- biological
- methylation
- prostate
- prostate-specific antigen
- prostatic neoplasms
- tumor markers
ASJC Scopus subject areas
- Urology