Development and evaluation of the MiCheck test for aggressive prostate cancer

Neal D. Shore, Christopher M. Pieczonka, R. Jonathan Henderson, James L. Bailen, Daniel R. Saltzstein, Raoul S. Concepcion, Jennifer L. Beebe-Dimmer, Julie J. Ruterbusch, Rachel A. Levin, Sandra Wissmueller, Thao Ho Le, David Gillatt, Daniel W. Chan, Douglas H. Campbell, Bradley J. Walsh

Research output: Contribution to journalArticle

Abstract

Background: 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. Objectives: To develop a blood test for AgCaP and compare to PSA, %free PSA, proPSA, and prostate health index (PHI) tests. Design, settings and participants: Patient samples from the MiCheck-01 trial were used for development of the MiCheck test. Methods: Serum analyte concentrations for cellular growth factors were determined using a custom-made Luminex-based R&D Systems multianalyte kit. Outcome measurements and statistical analysis: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)683.e11-683.e18
JournalUrologic Oncology: Seminars and Original Investigations
Volume38
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Aggressive
  • Biomarker
  • Clinical study
  • Prostate

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Development and evaluation of the MiCheck test for aggressive prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Shore, N. D., Pieczonka, C. M., Henderson, R. J., Bailen, J. L., Saltzstein, D. R., Concepcion, R. S., Beebe-Dimmer, J. L., Ruterbusch, J. J., Levin, R. A., Wissmueller, S., Le, T. H., Gillatt, D., Chan, D. W., Campbell, D. H., & Walsh, B. J. (2020). Development and evaluation of the MiCheck test for aggressive prostate cancer. Urologic Oncology: Seminars and Original Investigations, 38(8), 683.e11-683.e18. https://doi.org/10.1016/j.urolonc.2020.03.010