MP17-11 REFINEMENT AND EXTERNAL VALIDATION OF A NOVEL MULTIPLEX URINE TEST FOR HIGH-GRADE PROSTATE CANCER (2023)

You have accessJournal of UrologyCME1 Apr 2023MP17-11 REFINEMENT AND EXTERNAL VALIDATION OF A NOVEL MULTIPLEX URINE TEST FOR HIGH-GRADE PROSTATE CANCER Nathan Samora, Yuping Zhang, Lanbo Xiao, Heng Zheng, Cassie Xie, Bruce Trock, Javed Siddiqui, Lakshmi Kunju, Yashar Niknafs, Zoey Chopra, Grace Herron, Neil Vaishampayan, Kumaran Arivoli, Simpa Salami, Todd Morgan, Ganesh Palapattu, Yingye Zheng, John Wei, Arul Chinnaiyan, and Jeffrey Tosoian Nathan SamoraNathan Samora More articles by this author , Yuping ZhangYuping Zhang More articles by this author , Lanbo XiaoLanbo Xiao More articles by this author , Heng ZhengHeng Zheng More articles by this author , Cassie XieCassie Xie More articles by this author , Bruce TrockBruce Trock More articles by this author , Javed SiddiquiJaved Siddiqui More articles by this author , Lakshmi KunjuLakshmi Kunju More articles by this author , Yashar NiknafsYashar Niknafs More articles by this author , Zoey ChopraZoey Chopra More articles by this author , Grace HerronGrace Herron More articles by this author , Neil VaishampayanNeil Vaishampayan More articles by this author , Kumaran ArivoliKumaran Arivoli More articles by this author , Simpa SalamiSimpa Salami More articles by this author , Todd MorganTodd Morgan More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , Yingye ZhengYingye Zheng More articles by this author , John WeiJohn Wei More articles by this author , Arul ChinnaiyanArul Chinnaiyan More articles by this author , and Jeffrey TosoianJeffrey Tosoian More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The MyProstateScore (MPS) test employs the long non-coding RNA PCA3 and the TMPRSS2:ERG (T2:ERG) gene fusion to detect clinically-significant (Grade Group [GG]≥2) prostate cancer (PCa). To build upon MPS, we analyzed RNA-seq data from a PCa compendium, identifying 50 additional cancer- and high-grade cancer-specific markers. In total, 54 transcripts were measured by multiplex qPCR in 1504 urine biospecimens. The current study sought to develop and validate a novel urinary test for improved detection of GG≥2 PCa. METHODS: The 54-marker qPCR panel was assessed in a development cohort of men undergoing biopsy at the University of Michigan. The development cohort was divided into four subsets over ten iterations for glmnet modeling, identifying 17 markers independently contributing to discriminative accuracy. Acknowledging varying availability of patient-level clinical data (c) and prostate volume (v) in clinical practice, three novel MyProstateScore 2.0 models were developed: i) markers-only (MPS2), ii) markers and clinical data (MPS2c), and iii) markers, clinical data, and prostate volume (MPS2cv). The locked MPS2 models were provided to external analysts for validation in a blinded, multi-institutional NCI-EDRN biopsy cohort. RESULTS: Model development included 761 men with PSA 3-10 ng/ml, of whom 293 (39%) were found to have GG≥2 cancer on biopsy. The existing MPS test provided an area under the receiver operating characteristic curve (AUC) of 0.73, while the MPS2, MPS2c, and MPS2cv models yielded cross-validated AUC values of 0.78, 0.80, and 0.82, respectively. In the external validation cohort of 743 men with PSA 3-10 ng/ml, of which 151 (20%) were found to have GG≥2 cancer, the existing MPS test yielded an AUC of 0.73. The MPS2, MPS2c, and MPS2cv models yielded AUC values of 0.75, 0.81, and 0.82, respectively. At test thresholds providing 95% sensitivity, MPS provided 17% specificity, while the novel MPS2cv model provided 38% specificity. CONCLUSIONS: Incorporating novel transcripts associated with high-grade cancer, we externally validated a 17-marker urinary panel for detection of GG≥2 PCa. Compared to the clinically-available MPS test, the MPS2cv model improved diagnostic accuracy (AUC) by nearly 10% and increased specificity by 21% at clinically-actionable, highly-sensitive thresholds. These findings suggest that the MPS2 test meaningfully improves detection of GG≥2 PCa relative to current diagnostic tests and could contribute to a more optimal contemporary diagnostic pathway. Source of Funding: This work was funded by the Prostate Cancer Foundation Young Investigator Award (20YOUN11), the Early Detection Research Network (U01CA214170, U2CCA271854), the NCI Prostate SPORE (P50CA186786), and an NCI Outstanding Investigator Award (R35CA231996). We would like to acknowledge the EDRN PCA3 cohort study investigators and coordinators for their contribution to this work © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e217 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nathan Samora More articles by this author Yuping Zhang More articles by this author Lanbo Xiao More articles by this author Heng Zheng More articles by this author Cassie Xie More articles by this author Bruce Trock More articles by this author Javed Siddiqui More articles by this author Lakshmi Kunju More articles by this author Yashar Niknafs More articles by this author Zoey Chopra More articles by this author Grace Herron More articles by this author Neil Vaishampayan More articles by this author Kumaran Arivoli More articles by this author Simpa Salami More articles by this author Todd Morgan More articles by this author Ganesh Palapattu More articles by this author Yingye Zheng More articles by this author John Wei More articles by this author Arul Chinnaiyan More articles by this author Jeffrey Tosoian More articles by this author Expand All Advertisement PDF downloadLoading ...