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Cited by 179Prostate Cancer Diagnosis and TreatmentProstate Cancer Treatment and ResearchBreast Cancer Treatment Studies

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Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer

Blume-Jensen, Peter, Berman, David M., Rimm, David L., Shipitsin, Michail, Putzi, Mathew, Nifong, Thomas P., Small, Clayton, Choudhury, Sibgat, Capela, Teresa, Coupal, Louis, Ernst, Christina, Hurley, Aeron, Kaprelyants, Alex, Chang, Hua, Giladi, Eldar, Nardone, Julie, Dunyak, James, Loda, Massimo, Klein, Eric A., Magi-Galluzzi, Cristina, Latour, Mathieu, Epstein, Jonathan I., Kantoff, Philip, Saad, Fred·2015·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-14-2603

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Abstract

Purpose: Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction leading primarily to overtreatment and also missed opportunities for curative therapy. Experimental Design: An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay's ability to distinguish “favorable” versus “nonfavorable” pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D'Amico). Results: A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on “false-negative” and “false-positive” rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D'Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non–GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95). Conclusions: The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy. Clin Cancer Res; 21(11); 2591–600. ©2015 AACR.

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Metadata

Authors
Blume-Jensen, P., Berman, D. M., Rimm, D. L., Shipitsin, M., Putzi, M., Nifong, T. P., Small, C., Choudhury, S., Capela, T., Coupal, L., Ernst, C., Hurley, A., Kaprelyants, A., Chang, H., Giladi, E., Nardone, J., Dunyak, J., Loda, M., Klein, E. A., Magi-Galluzzi, C., Latour, M., Epstein, J. I., Kantoff, P., & Saad, F.
Affiliations
  • 1Metamark Genetics Inc., Cambridge, Massachusetts.
  • Queen's University (CA)
  • Yale University (US)
  • 4Urology Austin, Austin, Texas.
  • 5Impacts Inc., Montreal, Quebec, Canada.
  • Dana-Farber Cancer Institute (US)
  • Cleveland Clinic (US)
  • 8Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Johns Hopkins University (US)
  • 9Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2015-05-31
Volume
21
Issue
11
Pages
2591-2600
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-14-2603
OpenAlex
W2025795030
Cited by
179
References
0
Citations by year
2026: 8 · 2025: 6 · 2024: 12 · 2023: 8 · 2022: 23 · 2021: 18 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 27 · 2016: 24 · 2015: 6
FWCI
21.62
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Comprehensive Cancer Network
  • National Cancer Institute (P30CA008748)
Topics
  • Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
prostate cancer, risk stratification, proteomic biomarkers, prostate pathology, Gleason score, NCCN risk classification, D'Amico risk classification, prognostic factors, overtreatment, prostatectomy specimens
MeSH terms
Aged, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Prostatectomy, Prostatic Neoplasms, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Prostate-Specific Antigen, Risk Assessment, Proteomics

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