Mark Stovsky1,2, Eric A Klein1, Arnon Chait2, Kannan Manickam3, Andrew J Stephenson1, Mathew Wagner4, Martin Dineen5, Yair Lotan6, Alan Partin7, Jack Baniel8, Aimee Kestranek2, Prasad Gawande2. 1. Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic , Cleveland , Ohio. 2. Cleveland Diagnostics, Inc. , Cleveland , Ohio. 3. Chesapeake Urology Associates , Baltimore , Maryland. 4. Kaiser Permanente Northwest , Clackamas , Oregon. 5. Advanced Urology Institute , Daytona Beach , Florida. 6. University of Texas Southwestern Medical Center , Dallas , Texas. 7. The Brady Urological Institute, The Johns Hopkins University , Baltimore , Maryland. 8. Rabin Medical Center , Petah-Tikva , Israel.
Abstract
PURPOSE: Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort. MATERIALS AND METHODS: We performed a multicenter prospective validation in 271 men scheduled for prostate biopsy at a total of 7 academic and community centers who were enrolled between May 2017 and March 2018. Blood samples were obtained for assay prior to biopsy. The discrimination power of the assay to detect high grade prostate cancer (Gleason 7 or greater) was evaluated by ROC analysis and compared to prior results. Clinical performance was further improved by comparison with multiparametric magnetic resonance imaging-ultrasound vs transrectal ultrasound guided biopsies. RESULTS: The assay AUC was 0.784 for high grade vs low grade cancer/benign histology, which was superior to the AUCs of total prostate specific antigen and percent free prostate specific antigen. If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high grade cancers, of which 7 would have been Gleason sum 4 + 3 or higher. Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831. CONCLUSIONS: Validation of the structure based IsoPSA assay demonstrated statistical concordance with previously reported results and verified its superior performance vs concentration based prostate specific antigen and the free-to-total prostate specific antigen ratio. The assay improvement in detecting high grade prostate cancer using multiparametric magnetic resonance imaging-ultrasound guided biopsy may help define a new diagnostic paradigm.
PURPOSE: Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort. MATERIALS AND METHODS: We performed a multicenter prospective validation in 271 men scheduled for prostate biopsy at a total of 7 academic and community centers who were enrolled between May 2017 and March 2018. Blood samples were obtained for assay prior to biopsy. The discrimination power of the assay to detect high grade prostate cancer (Gleason 7 or greater) was evaluated by ROC analysis and compared to prior results. Clinical performance was further improved by comparison with multiparametric magnetic resonance imaging-ultrasound vs transrectal ultrasound guided biopsies. RESULTS: The assay AUC was 0.784 for high grade vs low grade cancer/benign histology, which was superior to the AUCs of total prostate specific antigen and percent free prostate specific antigen. If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high grade cancers, of which 7 would have been Gleason sum 4 + 3 or higher. Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831. CONCLUSIONS: Validation of the structure based IsoPSA assay demonstrated statistical concordance with previously reported results and verified its superior performance vs concentration based prostate specific antigen and the free-to-total prostate specific antigen ratio. The assay improvement in detecting high grade prostate cancer using multiparametric magnetic resonance imaging-ultrasound guided biopsy may help define a new diagnostic paradigm.
Entities:
Keywords:
biomarkers; neoplasm grading; prostate specific antigen; prostatic neoplasms; protein isoforms; tumor
Authors: Rafael D Melani; Vincent R Gerbasi; Lissa C Anderson; Jacek W Sikora; Timothy K Toby; Josiah E Hutton; David S Butcher; Fernanda Negrão; Henrique S Seckler; Kristina Srzentić; Luca Fornelli; Jeannie M Camarillo; Richard D LeDuc; Anthony J Cesnik; Emma Lundberg; Joseph B Greer; Ryan T Fellers; Matthew T Robey; Caroline J DeHart; Eleonora Forte; Christopher L Hendrickson; Susan E Abbatiello; Paul M Thomas; Andy I Kokaji; Josh Levitsky; Neil L Kelleher Journal: Science Date: 2022-01-27 Impact factor: 63.714