Mp17-08 clinical validation of a novel six-gene risk-stratification signature to support treatment decisions for men diagnosed with prostate cancer

You have accessJournal of UrologyCME1 Apr 2023MP17-08 CLINICAL VALIDATION OF A NOVEL SIX-GENE RISK-STRATIFICATION SIGNATURE TO SUPPORT TREATMENT DECISIONS FOR MEN DIAGNOSED WITH PROSTATE CANCER Agnieszka Krzyzanowska, Stephen Barron, Debra F. Higgins, Tony Loughman, Katherine M. Sheehan, Angel Chan-Ju Wang, Bozena Fender, Leah M. McGuire, David Galvin, Amanda O'Neil, Joanna Fay, Anthony O'Grady, Desmond O'Leary, R. William. G. Watson, Anders Bjartell, and William M. Gallagher Agnieszka KrzyzanowskaAgnieszka Krzyzanowska More articles by this author , Stephen BarronStephen Barron More articles by this author , Debra F. HigginsDebra F. Higgins More articles by this author , Tony LoughmanTony Loughman More articles by this author , Katherine M. SheehanKatherine M. Sheehan More articles by this author , Angel Chan-Ju WangAngel Chan-Ju Wang More articles by this author , Bozena FenderBozena Fender More articles by this author , Leah M. McGuireLeah M. McGuire More articles by this author , David GalvinDavid Galvin More articles by this author , Amanda O'NeilAmanda O'Neil More articles by this author , Joanna FayJoanna Fay More articles by this author , Anthony O'GradyAnthony O'Grady More articles by this author , Desmond O'LearyDesmond O'Leary More articles by this author , R. William. G. WatsonR. William. G. Watson More articles by this author , Anders BjartellAnders Bjartell More articles by this author , and William M. GallagherWilliam M. Gallagher More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is diagnosed in over 1.2 million men worldwide annually. Most men have indolent PCa and can safely defer treatment with active surveillance. However, many men are commonly treated with surgery or radiation therapy which are associated with reduced quality of life. Clinicians are increasingly using molecular information to further understand a patient’s risk of aggressive PCa, and while these signatures have shown promise, there remains a significant opportunity for improving prognostic capacity. METHODS: Expression of a novel six-gene signature was measured by RT-qPCR in prostate samples from an Irish cohort of men diagnosed with PCa and treated with radical prostatectomy (RP) (PCRC, n=426). Cross-validated logistic regression identified a six-gene molecular risk score (MRS) with strong prognostic performance to predict aggressive PCa. The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score to create a molecular plus clinical risk score (MCRS). The MRS and MCRS were clinically validated in an independent Swedish cohort of men diagnosed with PCa and treated by RP (UPCA, n=203 RP and n=100 biopsy samples). RESULTS: We identified a six-gene signature, four prognostic and two reference genes, with improved prognostic value over clinical features. In the clinical biopsy validation study, the AUC of the signature for AP was 0.72 (MRS) and 0.82 (MCRS) versus 0.72 (EAU) and 0.82 (CAPRA), and for high primary Gleason was 0.75 (MRS) and 0.85 (MCRS) versus 0.77 (EAU) and 0.83 (CAPRA). The C index for BCR was 0.62 (MRS) and 0.74 (MCRS) versus 0.65 (EAU) and 0.73 (CAPRA). In bivariable analysis, the six-gene signature added statistically significant (p<0.001) prognostic value to EAU and CAPRA. In the RP clinical validation study, the C index for BCR was 0.74 (MRS) and 0.83 (MCRS) versus 0.69 (EAU) and 0.77 (CAPRA). In bivariable analysis, the six-gene signature added statistically significant (p<0.0001) prognostic value to EAU and CAPRA. CONCLUSIONS: The six-gene molecular prognostic signature has strong performance for AP, high primary Gleason and BCR in independent clinical validation studies when tested on prostate biopsy or RP tissue. MCRS provides improved prognostic stratification and can inform optimal patient management post-diagnosis and post-treatment. Source of Funding: Support is acknowledged from the Swedish Cancer Society, the Swedish Scientific Council and Government Funding of Clinical Research within the Swedish National Health Service (ALF), the Irish Cancer Society, and OncoAssure Ltd © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e215 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Agnieszka Krzyzanowska More articles by this author Stephen Barron More articles by this author Debra F. Higgins More articles by this author Tony Loughman More articles by this author Katherine M. Sheehan More articles by this author Angel Chan-Ju Wang More articles by this author Bozena Fender More articles by this author Leah M. McGuire More articles by this author David Galvin More articles by this author Amanda O'Neil More articles by this author Joanna Fay More articles by this author Anthony O'Grady More articles by this author Desmond O'Leary More articles by this author R. William. G. Watson More articles by this author Anders Bjartell More articles by this author William M. Gallagher More articles by this author Expand All Advertisement PDF downloadLoading ...