James McKiernan1, Michael J Donovan2, Eric Margolis3, Alan Partin4, Ballentine Carter4, Gordon Brown5, Phillipp Torkler6, Mikkel Noerholm6, Johan Skog7, Neal Shore8, Gerry Andriole9, Ian Thompson10, Peter Carroll11. 1. Department of Urology, Columbia University Medical Center, New York City, NY, USA. 2. Icahn School of Medicine at Mt. Sinai, New York City, NY, USA. Electronic address: michael.donovan@mssm.edu. 3. Urology Center of Englewood, Englewood, NJ, USA. 4. The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Delaware Valley Urology, Vorhees, NJ, USA. 6. Exosome Diagnostics GmbH, Martinsried, Germany. 7. Exosome Diagnostics Inc, Waltham, MA, USA. 8. Atlantic Urology Clinics, Myrtle Beach, SC, USA. 9. Division of Urologic Surgery, Department of Surgery and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. 10. UT Health Science Center, San Antonio, TX, USA. 11. Department of Urology, University of California at San Francisco, CA, USA.
Abstract
BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of 64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n=519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. PATIENT SUMMARY: It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2-10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator's and standard clinical data.
BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of 64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n=519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. PATIENT SUMMARY: It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2-10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator's and standard clinical data.
Authors: J Woo; S Santasusagna; J Banks; S Pastor-Lopez; K Yadav; M Carceles-Cordon; A Dominguez-Andres; R B Den; L R Languino; R Pippa; C D Lallas; G Lu-Yao; W K Kelly; K E Knudsen; V Rodriguez-Bravo; A K Tewari; J M Prats; B E Leiby; L G Gomella; Josep Domingo-Domenech Journal: J Urol Date: 2020-04-06 Impact factor: 7.450
Authors: Anudeep Yekula; Koushik Muralidharan; Keiko M Kang; Lan Wang; Leonora Balaj; Bob S Carter Journal: Methods Date: 2020-02-12 Impact factor: 3.608
Authors: Anudeep Yekula; Koushik Muralidharan; Zachary S Rosh; Anna E Youngkin; Keiko M Kang; Leonora Balaj; Bob S Carter Journal: Adv Biosyst Date: 2020-06-02
Authors: Rania El Fekih; James Hurley; Vasisht Tadigotla; Areej Alghamdi; Anand Srivastava; Christine Coticchia; John Choi; Hazim Allos; Karim Yatim; Juliano Alhaddad; Siawosh Eskandari; Philip Chu; Albana B Mihali; Isadora T Lape; Mauricio P Lima Filho; Bruno T Aoyama; Anil Chandraker; Kassem Safa; James F Markmann; Leonardo V Riella; Richard N Formica; Johan Skog; Jamil R Azzi Journal: J Am Soc Nephrol Date: 2021-03-03 Impact factor: 10.121