Development and clinical validation of an in situ biopsy based multi-marker assay for risk stratification in prostate cancer - 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 over-treatment but 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 'non-favorable' pathology independently and relative to current risk classification systems (NCCN and D'Amico).

Results: A favorable biomarker risk score of ≤ 0.33, and a non-favorable 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- 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 non-favorable 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 co-primary endpoints, separating favorable from non-favorable pathology (AUC, 0.68, P< 0.0001, odds ratio=20.9) and GS-6 versus non-GS-6 pathology (AUC, 0.65, P< 0.0001, OR=12.95).

Conclusion: 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.

Written by:
Blume-Jensen P, Berman D, Rimm DL, Shipitsin M, Putzi M, Nifong TP, Small C, Choudhury S, Capela T, Coupal L, Ernst C, Hurley AD, Kaprelyants A, Chang H4, Giladi E, Nardone J, Dunyak J, Loda M, Klein EA, Magi-Galluzzi C, Latour M, Epstein JI, Kantoff P, Saad F.   Are you the author?
CSO, Metamark Genetics; Pathology and Molecular Medicine, Queens University; Dept of Pathology, Yale University School of Medicine; Research & Development, Metamark Genetics; Urology, Urology Austin; Clinical Laboratory, Metamark Genetics; Biostatistics, Impacts Inc; Informatics, Atreca; Medical Oncology, Dana-Farber Cancer Institute; Glickman Urological and Kidney Institute, Cleveland Clinic Foundation; Anatomical Pathology, Cleveland Clinic Foundation; Pathology, Centre Hospitalier de l'Université de Montréal; Pathology, Johns Hopkins Medicine; CRCHUM, Université de Montréal.  

Reference: Clin Cancer Res. 2015 Mar 2. pii: clincanres.2603.2014.
doi: 10.1158/1078-0432.CCR-14-2603

PubMed Abstract
PMID: 25733599 Prostate Cancer Section