Development and evaluation of the MiCheck® Prostate test for clinically significant prostate cancer.
Biomarker
Clinical study
Clinically significant cancer
NPV
Prostate
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
23
04
2023
revised:
03
08
2023
accepted:
09
08
2023
medline:
5
12
2023
pubmed:
22
9
2023
entrez:
21
9
2023
Statut:
ppublish
Résumé
There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer. To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set. About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP. Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm. Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer. The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10. The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer.
OBJECTIVES
OBJECTIVE
To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set.
DESIGN, SETTINGS, AND PARTICIPANTS
METHODS
About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP.
METHODS
METHODS
Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer.
RESULTS
RESULTS
The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10.
CONCLUSIONS
CONCLUSIONS
The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis.
Identifiants
pubmed: 37734979
pii: S1078-1439(23)00265-X
doi: 10.1016/j.urolonc.2023.08.005
pii:
doi:
Substances chimiques
Prostate-Specific Antigen
EC 3.4.21.77
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
454.e9-454.e16Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Neal D. Shore has neither equity nor salary with Minomic. The author has received honorarium as a consultant/advisor.