TY - JOUR
T1 - Development and evaluation of the MiCheck test for aggressive prostate cancer
AU - Shore, Neal D.
AU - Pieczonka, Christopher M.
AU - Henderson, R. Jonathan
AU - Bailen, James L.
AU - Saltzstein, Daniel R.
AU - Concepcion, Raoul S.
AU - Beebe-Dimmer, Jennifer L.
AU - Ruterbusch, Julie J.
AU - Levin, Rachel A.
AU - Wissmueller, Sandra
AU - Le, Thao Ho
AU - Gillatt, David
AU - Chan, Daniel W.
AU - Campbell, Douglas H.
AU - Walsh, Bradley J.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Aggressive
KW - Biomarker
KW - Clinical study
KW - Prostate
UR - http://www.scopus.com/inward/record.url?scp=85083294523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083294523&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2020.03.010
DO - 10.1016/j.urolonc.2020.03.010
M3 - Article
C2 - 32305266
AN - SCOPUS:85083294523
SN - 1078-1439
VL - 38
SP - 683.e11-683.e18
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 8
ER -