Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer

Mark Stovsky, Eric A. Klein, Arnon Chait, Kannan Manickam, Andrew J. Stephenson, Mathew Wagner, Martin Dineen, Yair Lotan, Alan Partin, Jack Baniel, Aimee Kestranek, Prasad Gawande, Zaslavsky Boris Zaslavsky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1115-1120
Number of pages6
JournalThe Journal of urology
Volume201
Issue number6
DOIs
StatePublished - Jun 1 2019

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Prostate-Specific Antigen
Prostatic Neoplasms
Biopsy
Image-Guided Biopsy
Area Under Curve
Magnetic Resonance Imaging
Neoplasms
ROC Curve
Prostate
Histology
Protein Isoforms

Keywords

  • biomarkers
  • neoplasm grading
  • prostate specific antigen
  • prostatic neoplasms
  • protein isoforms
  • tumor

ASJC Scopus subject areas

  • Urology

Cite this

Stovsky, M., Klein, E. A., Chait, A., Manickam, K., Stephenson, A. J., Wagner, M., ... Boris Zaslavsky, Z. (2019). Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer. The Journal of urology, 201(6), 1115-1120. https://doi.org/10.1097/JU.0000000000000185

Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer. / Stovsky, Mark; Klein, Eric A.; Chait, Arnon; Manickam, Kannan; Stephenson, Andrew J.; Wagner, Mathew; Dineen, Martin; Lotan, Yair; Partin, Alan; Baniel, Jack; Kestranek, Aimee; Gawande, Prasad; Boris Zaslavsky, Zaslavsky.

In: The Journal of urology, Vol. 201, No. 6, 01.06.2019, p. 1115-1120.

Research output: Contribution to journalArticle

Stovsky, M, Klein, EA, Chait, A, Manickam, K, Stephenson, AJ, Wagner, M, Dineen, M, Lotan, Y, Partin, A, Baniel, J, Kestranek, A, Gawande, P & Boris Zaslavsky, Z 2019, 'Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer', The Journal of urology, vol. 201, no. 6, pp. 1115-1120. https://doi.org/10.1097/JU.0000000000000185
Stovsky, Mark ; Klein, Eric A. ; Chait, Arnon ; Manickam, Kannan ; Stephenson, Andrew J. ; Wagner, Mathew ; Dineen, Martin ; Lotan, Yair ; Partin, Alan ; Baniel, Jack ; Kestranek, Aimee ; Gawande, Prasad ; Boris Zaslavsky, Zaslavsky. / Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer. In: The Journal of urology. 2019 ; Vol. 201, No. 6. pp. 1115-1120.
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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.",
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N2 - 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.

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