2 Background: Active surveillance is an increasing alternative for the management of low risk prostate cancer; however, there is a crucial need for better biomarkers to distinguish men with indolent versus aggressive disease. Both PCA3 and TMRPSS2-ERG (T2-ERG) are biomarkers that show promise in that they may be associated with more aggressive disease. This study examines the correlation of these biomarkers with higher volume or grade cancer in an active surveillance cohort. Methods: Post-DRE urine was collected prospectively as part of the multi-institutional Canary/EDRN Prostate Active Surveillance Study (PASS). PCA3 and T2-ERG levels were analyzed in urine collected from 401 men at study entry. Many of the men had undergone previous biopsies after initial prostate cancer diagnosis, and 20% of the urine specimens were associated with a negative serial biopsy. Biomarker scores were correlated to clinical and pathologic variables, including tumor volume - measured by percent of biopsy core involvement - and Gleason score, using non-parametric and univariate analyses. Results: Both PCA3 and T2-ERG scores were significantly associated with higher volume disease. For negative repeat biopsy, 1-10%, 11-34%, >34% positive cores, median (95% CI) PCA3 scores were 27 (24-31), 26 (22-33), 40 (29-51), 47 (26-90), p = 0.003 [Kruskal Wallis test (KW)], and median T2-ERG scores were 5 (2-8), 9 (4-14), 21 (14-40), 23 (4-115), p < 0.0001 (KW). Both PCA3 and T2-ERG scores were also significantly associated with presence of higher grade disease. For negative biopsy, Gleason 5 - 6, and Gleason >7, the median PCA3 scores were 27 (24-31), 31 (27-35), 48 (31-92), p = 0.02 (KW), and median T2-ERG scores were 5 (2-8), 14 (9-18), 29 (13-78), p = 0.001 (KW). The odds ratio for a positive biopsy versus a negative biopsy (ref) on modeling was 1.37 (1.04-1.81), p = 0.02 for PCA3 and 1.30 (1.12-1.51), p = 0.0006 for T2-ERG. Conclusions: Both PCA3 and T2-ERG appear to stratify risk, for men on active surveillance, of having aggressive cancer as defined by tumor volume or Gleason score and may have clinical applicability in selecting men with low volume/low grade disease for active surveillance.
Complications after prostate biopsies in men on active surveillance and its effects on receiving further biopsies in the Prostate cancer Research International: Active Surveillance (PRIAS) study
