Abstract A32: A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies

Abstract

Abstract Background: Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. Methods: We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with PSAD to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic “gray zone” (4–10 ng/ml) on a target subset of 82 men with no prior biopsy. Results: By univariate analysis, we found that the PSMA, PSGR, PCA3 and PSAD scores were significant predictors of PCa. Using a multiplex model, the area under the multireceiver operating characteristic curve was 0.80 versus 0.89 in the diagnostic gray zone. Fixing the sensitivity at 96%, we obtained a specificity of 40% and 62% in the gray zone. By this approach it would be possible to save approximately 35% of unnecessary biopsies with a sensitivity of 95%. Conclusions: Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Citation Format: Marina Rigau, Tatiana Altadill, Andreas Doll, Tamara Sequeiros, Mireia Olivan, Marta Garcia, Alex Sanchez, Melania Montes, Israel Ortega, Juan Morote, Jaume Reventos. A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A32.