Development and evaluation of the MiCheck test for aggressive prostate cancer

Neal  D Shore; Dmitry M. Polikarpov; 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 A. Gillatt; Daniel  W. Chan; Niantao  Deng; Jaya Sowjanya Siddireddy; Yanling  Lu; Douglas  H. Campbelle; Bradley  J. Walsh

doi:10.1016/j.urolonc.2020.03.010

Development and evaluation of the MiCheck test for aggressive prostate cancer

Neal D Shore
, Dmitry M. Polikarpov
, 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 A. Gillatt
, Daniel W. Chan
, Niantao Deng
, Jaya Sowjanya Siddireddy
, Yanling Lu
, Douglas H. Campbelle
, Bradley J. Walsh

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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 language	English
Pages (from-to)	683.e11-683.e18
Number of pages	8
Journal	Urologic Oncology: seminars and original investigations
Volume	38
Issue number	8
DOIs	https://doi.org/10.1016/j.urolonc.2020.03.010
Publication status	E-pub ahead of print - Sept 2023
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.urolonc.2020.03.010

Cite this

D Shore, N., M. Polikarpov, D., M Pieczonka, C., Henderson, R. J., L Bailen, J., R. Saltzstein, D., S. Concepcion, R., L. Beebe-Dimmer, J., J. Ruterbusch, J., A. Levin, R., Wissmueller, S., Ho Le, T., A. Gillatt, D., W. Chan, D., Deng, N., Siddireddy, J. S., Lu, Y., H. Campbelle, D., & J. Walsh, B. (2023). Development and evaluation of the MiCheck test for aggressive prostate cancer. Urologic Oncology: seminars and original investigations, 38(8), 683.e11-683.e18. Advance online publication. https://doi.org/10.1016/j.urolonc.2020.03.010

@article{88a1d39a652d40f690eaf8b5b99cfec2,

title = "Development and evaluation of the MiCheck test for aggressive prostate cancer",

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.",

keywords = "Aggressive, Biomarker, Clinical study, Prostate",

author = "\{D Shore\}, Neal and \{M. Polikarpov\}, Dmitry and \{M Pieczonka\}, Christopher and Henderson, \{R Jonathan\} and \{L Bailen\}, James and \{R. Saltzstein\}, Daniel and \{S. Concepcion\}, Raoul and \{L. Beebe-Dimmer\}, Jennifer and \{J. Ruterbusch\}, Julie and \{A. Levin\}, Rachel and Sandra Wissmueller and \{Ho Le\}, Thao and \{A. Gillatt\}, David and \{W. Chan\}, Daniel and Niantao Deng and Siddireddy, \{Jaya Sowjanya\} and Yanling Lu and \{H. Campbelle\}, Douglas and \{J. Walsh\}, Bradley",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2023",

month = sep,

doi = "10.1016/j.urolonc.2020.03.010",

language = "English",

volume = "38",

pages = "683.e11--683.e18",

journal = "Urologic Oncology: seminars and original investigations",

issn = "1078-1439",

publisher = "Elsevier Inc.",

number = "8",

}

D Shore, N, M. Polikarpov, D, M Pieczonka, C, Henderson, RJ, L Bailen, J, R. Saltzstein, D, S. Concepcion, R, L. Beebe-Dimmer, J, J. Ruterbusch, J, A. Levin, R, Wissmueller, S, Ho Le, T, A. Gillatt, D, W. Chan, D, Deng, N, Siddireddy, JS, Lu, Y, H. Campbelle, D & J. Walsh, B 2023, 'Development and evaluation of the MiCheck test for aggressive prostate cancer', Urologic Oncology: seminars and original investigations, vol. 38, no. 8, pp. 683.e11-683.e18. https://doi.org/10.1016/j.urolonc.2020.03.010

TY - JOUR

T1 - Development and evaluation of the MiCheck test for aggressive prostate cancer

AU - D Shore, Neal

AU - M. Polikarpov, Dmitry

AU - M Pieczonka, Christopher

AU - Henderson, R Jonathan

AU - L Bailen, James

AU - R. Saltzstein, Daniel

AU - S. Concepcion, Raoul

AU - L. Beebe-Dimmer, Jennifer

AU - J. Ruterbusch, Julie

AU - A. Levin, Rachel

AU - Wissmueller, Sandra

AU - Ho Le, Thao

AU - A. Gillatt, David

AU - W. Chan, Daniel

AU - Deng, Niantao

AU - Siddireddy, Jaya Sowjanya

AU - Lu, Yanling

AU - H. Campbelle, Douglas

AU - J. Walsh, Bradley

PY - 2023/9

Y1 - 2023/9

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 - https://www.scopus.com/pages/publications/85083294523

U2 - 10.1016/j.urolonc.2020.03.010

DO - 10.1016/j.urolonc.2020.03.010

M3 - Article

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 -

Development and evaluation of the MiCheck test for aggressive prostate cancer

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this