Development and evaluation of the MiCheck test for aggressive prostate cancer

• Published in: Urologic oncology Vol. 38; no. 8; pp. 683.e11 - 683.e18
• Main Authors: Shore, Neal D., Pieczonka, Christopher M., Henderson, R. Jonathan, Bailen, James L., Saltzstein, Daniel R., Concepcion, Raoul S., Beebe-Dimmer, Jennifer L., Ruterbusch, Julie J., Levin, Rachel A., Wissmueller, Sandra, Le, Thao Ho, Gillatt, David, Chan, Daniel W., Campbell, Douglas H., Walsh, Bradley J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020
• Subjects: Aged; Aged, 80 and over; Aggressive; Biomarker; Clinical study; Hematologic Tests - statistics & numerical data; Humans; Male; Middle Aged; Monte Carlo Method; Neoplasm Grading; Prostate; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Biomarker; Aggressive; Prostate; Clinical study
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2020.03.010

•MiCheck test is a blood test developed to detect aggressive prostate cancer.•Uses an algorithm containing clinical factors and soluble analytes to give a risk score.•Outperforms existing tests in differentiating aggressive from nonaggressive prostate cancer.•Has potential to significantly reduce biopsies and healthcare costs. A clinical need exists for a biomarker test to accurately delineate aggressive prostate cancer (AgCaP), and thus better assist clinicians and patients decision-making on whether to proceed to prostate biopsy. To develop a blood test for AgCaP and compare to PSA, %free PSA, proPSA, and prostate health index (PHI) tests. Patient samples from the MiCheck-01 trial were used for development of the MiCheck test. Serum analyte concentrations for cellular growth factors were determined using a custom-made Luminex-based R&D Systems multianalyte kit. Bayesian model averaging and random forest approaches were used to identify clinical factors and growth factors able to distinguish between men with AgCaP (Gleason Score [GS] ≥3+4) from those with non-AgCaP (GS 3+3). Logistic regression and Monte Carlo cross-validation identified variable combinations in order to able to maximize differentiation of AgCaP from non-AgCaP. The MiCheck logistic regression model was developed and comprises the following variables: serum prostate-specific antigen (PSA), patient age, Digital Rectal Exam (DRE) status, Leptin, IL-7, vascular endothelial growth factor, and Glypican-1. The model differentiated AgCaP from non-AgCaP with an area under the curve of 0.83 and was superior to PSA, %free PSA and PHI in all patient groups, regardless of PSA range. Applying the MiCheck test to all evaluable biopsy patients from the MiCheck-01 study demonstrated that up to 30% of biopsies could be avoided while delaying diagnosis of only 6.8% of GS ≥3+4 cancers, 5% of GS ≥4+3 cancers and no cancers of GS 8 or higher. The MiCheck test outperforms PSA, %free PSA and PHI tests in differentiating AgCaP vs. non-AgCaP patients. The MiCheck test could result in a significant number of biopsies being avoided with a low number of patients experiencing a delayed diagnosis.