LAUSR

58 Background: Distinguishing indolent from aggressive prostate cancer remains a key challenge for prostate cancer management decision-making. A growing number of biomarkers are now on the market to help address this need, but have rarely been examined together in the same patients to determine their relative value. Methods: We identified men with low-risk cancers defined by biopsy Gleason score ≤3+3, PSA ≤10ng/ml, and clinical stage ≤T2 who underwent immediate prostatectomy. We collected archived prostate tissue and pre-surgical plasma samples from N = 381 cases from UCSF and N = 279 cases from UW. Plasma was analyzed for TGFb1 and IL6SR, previously validated markers for prostate cancer prognosis, using ELISA. From prostate tissue, DNA and RNA were extracted and analyzed for the GEMCaP copy number variation score and the cell cycle progression (CCP) score, respectively, both well-validated and previously reported scores. Pathologic outcomes were minor (pGS 3+4 or pT3a) or major (pGS ≥4+3 or ≥pT3b) upgrading/upstaging (UGUS), and multinomial regression was performed to determine putative markers’ ability to predict these outcomes, controlling for PSA, percent of biopsy cores positive, age, and clinical site. Results: Overall, 357 men had no UGUS event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFb1 nor IL6SR statistically significantly predicted any UGUS or major UGUS. On the other hand, both CCP and GEMCaP were directly associated with minor UGUS on univariate analysis. On multivariable multinomial analysis including both scores, the CCP score predicted minor UGUS (OR 1.70, 95% CI 1.07-2.72, p = .03) and GEMCaP also predicted minor UGUS (OR 1.04, 95% CI 1.01-1.07, p < .01). Neither CCP nor GEMCaP predicted major UG/US, but the number of events was small. Noteworthy, both GEMCaP and the CCP score were statistically significant predictors of outcomes in the same model, suggesting they can complement each other by offering additional information. The other clinical parameters were not significant in this model. Conclusions: Biomarker signatures based on analysis of DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy.