A Novel Combination of Serum Markers in a Multivariate Model to Help Triage Patients Into “Low-” and “High-Risk” Categories for Prostate Cancer

Abstract

BackgroundAlmost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies.Materials and MethodsSerum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA).ResultsThe data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log10 IL-8, log10 MCP-1, and log10 tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA.ConclusionsThe novel combination of serum markers identified in this study could be employed to help triage patients into “low-” and “high-risk” categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments.