Abstract 899: TMPRSS2:ERG urine test identifies Gleason score upgrading and significant prostate cancer

Abstract

Objective: In men diagnosed with prostate cancer (PCa) at biopsy, a major challenge is correctly stratifying those with indolent versus significant PCa for treatment selection. The extent and grade of PCa is assessed in part based on standard risk factors, biopsy Gleason score (bx GS) and the number of positive biopsy cores. However, due to under-sampling at biopsy, upgrading in Gleason score is often seen from biopsy to prostatectomy. In this study we evaluated a TMPRSS2:ERG (T2:ERG) urine test for its ability to identify significant cancer and upgrading at prostatectomy. Methods: Post-DRE urine specimens were prospectively collected from 218 men referred for prostatectomy. T2:ERG mRNA copies were quantified using a transcription-mediated amplification assay and normalized to PSA mRNA copies to calculate a T2:ERG score. The prototype T2:ERG urine assay detects the gene fusion mRNA isoform TMPRSS2 exon 1 to ERG exon 4. T2:ERG score was correlated to prostatectomy Gleason score (px GS) and significant cancer as defined by the Epstein criteria at prostatectomy. Results: Of 185 men scheduled for radical prostatectomy, 61 had low risk of significant cancer based on having bx GS<6 and % positive biopsy cores<33%, yet upon prostatectomy, 57% of these men were found to harbor a significant PCa. The T2:ERG assay identified an additional 31% prostatectomy significant cancer in the biopsy low-risk disease cancer group. In a multivariate model, adding T2:ERG to bx GS and % positive cores significantly increased the accuracy for predicting significant PCa at prostatectomy from 0.84 to 0.89 (p=0.0002). Sensitivity increased by 8% for detecting prostatectomy significant cancer when T2:ERG was added to these biopsy criteria (sens/spec=85%/87% vs 77%/87%). T2:ERG also significantly correlated with Gleason score upgrading from biopsy to prostatectomy (bx GS/px GS = 6/ 6 vs bx GS/px GS = 6/>7, p = 0.0076). At biopsy, 70 men were found to have low-grade cancer (bx GS<6), but upon prostatectomy, upgrading was seen in 50% of these men. T2:ERG was able to identify 40% of men with bx GS<6 that were later upgraded. Conclusions: A T2:ERG urine test may help identify significant cancers and Gleason score upgrading, and increase predictive accuracy when used in combination with currently available methods. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 899. doi:10.1158/1538-7445.AM2011-899