2107 VALIDATION OF A CELL-CYCLE PROGRESSION GENE PANEL TO IMPROVE RISK-STRATIFICATION IN A CONTEMPORARY PROSTATECTOMY COHORT

Field: Medicine (Health Sciences)

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20122107 VALIDATION OF A CELL-CYCLE PROGRESSION GENE PANEL TO IMPROVE RISK-STRATIFICATION IN A CONTEMPORARY PROSTATECTOMY COHORT Matthew R. Cooperberg, Jeff Simko, Janet Cowan, Julia Reid, Kyle Kuchinsky, Satish Bhatnagar, Alexander Gutin, Jerry Lanchbury, Steven Stone, and Peter Carroll Matthew R. CooperbergMatthew R. Cooperberg San Francisco, CA , Jeff SimkoJeff Simko San Francisco, CA , Janet CowanJanet Cowan San Francisco, CA , Julia ReidJulia Reid Salt Lake City, UT , Kyle KuchinskyKyle Kuchinsky San Francisco, CA , Satish BhatnagarSatish Bhatnagar Salt Lake City, UT , Alexander GutinAlexander Gutin Salt Lake City, UT , Jerry LanchburyJerry Lanchbury Salt Lake City, UT , Steven StoneSteven Stone Salt Lake City, UT , and Peter CarrollPeter Carroll San Francisco, CA View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2275AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ongoing over-treatment of low-risk prostate cancer, and to a lesser extent under-treatment of occult high-risk disease, have contributed to an ongoing controversy regarding the relative risks and benefits of prostate cancer screening. Novel biomarkers are therefore needed which can help predict tumor behavior with greater accuracy, and thus facilitate better treatment decision-making. We aimed to validate a previously described risk score based on a 46-gene expression signature comprised of 31 cell-cycle progression genes (CCP genes) and 15 housekeepers for predicting outcome following radical prostatectomy (RP) in a contemporary cohort. METHODS Patients were eligible who underwent RP at UCSF since 1994 and had ≥5 years of follow-up. RNA was extracted from paraffin-embedded RP specimens and converted to cDNA. The CCP genes were amplified and quantified in triplicate, and the CCP score was calculated as the normalized average of CCP gene expression. Recurrence was defined as 2 PSAs ≥ 0.2 ng/ml or any second treatment at least 6 months after surgery. Associations between CCP score and recurrence were examined using univariate survival analysis and with adjustment for standard pathologic variables. The CCP score was assessed for its independent prognostic utility beyond a standard postoperative risk assessment tool (CAPRA-S). RESULTS 413 men were included, of whom 82 recurred. The hazard ratio (HR) for each unit increase in CCP score (range −1.62 to 2.16) was 2.1 (95% CI 1.6-2.9, p-value < 0.0001); with adjustment for age, year, preoperative PSA, pathologic Gleason score, staging parameters, the HR remained significant at 2.0 (1.4-2.8, p-value < 0.0001). The score was particularly able to sub-stratify patients with low clinical risk of recurrence as defined by CAPRA-S scores ≤2: HR 2.3 (1.4-3.7, p-value = 0.0027). By likelihood ratio testing, combining CAPRA-S and CCP score yielded a model that was significantly more prognostic than the CAPRA-S alone, both for the whole cohort and for the low-risk subset. Addition of the CCP score to the CAPRA-S improved the concordance (c) index from 0.74 to 0.77 for the overall cohort, and from 0.65 to 0.73 for the subset with low-risk disease. CONCLUSIONS In a contemporary RP cohort, the CCP score was validated to have significant prognostic accuracy even when controlling for all available clinical and pathologic data. The score has the potential to substantially improve accuracy of risk stratification, particularly among low-risk men. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e850 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew R. Cooperberg San Francisco, CA More articles by this author Jeff Simko San Francisco, CA More articles by this author Janet Cowan San Francisco, CA More articles by this author Julia Reid Salt Lake City, UT More articles by this author Kyle Kuchinsky San Francisco, CA More articles by this author Satish Bhatnagar Salt Lake City, UT More articles by this author Alexander Gutin Salt Lake City, UT More articles by this author Jerry Lanchbury Salt Lake City, UT More articles by this author Steven Stone Salt Lake City, UT More articles by this author Peter Carroll San Francisco, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...