Biology of Human Tumors Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer

Peter Blume-Jensen, David M. Berman, David L. Rimm, Michail Shipitsin, Mathew Putzi, Thomas P. Nifong, Clayton Small, Sibgat Choudhury, Teresa Capela, Louis Coupal, Christina Ernst, Aeron Hurley, Alex Kaprelyants, Hua Chang, Eldar Giladi, Julie Nardone, James Dunyak, Massimo Loda, Eric A. Klein, Cristina Magi-GalluzziMathieu Latour, Jonathan I. Epstein, Philip Kantoff, Fred Saad

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2591-2600
Number of pages10
JournalClinical Cancer Research
Issue number11
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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