See the published version of this preprint at BMC Urology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research article
Michael J Donovan
Icahn School of Medicine at Mt. Sinai
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0772-598X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.
Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.
Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.
Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.
Keywords
Prostate Cancer, Exosomes, Urine, early detection, prostate biopsy
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Urology.
No community comments so far
Editorial decision: Accept
On 25 Aug, 2020
Editor assigned
On 21 Aug, 2020
Submission checks complete
On 20 Aug, 2020
Editor invited
On 20 Aug, 2020
Version 2
Posted 13 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 19 Aug, 2020
Review #2 received
Received 17 Aug, 2020
Reviewer #1 agreed
On 11 Aug, 2020
Reviewer #2 agreed
On 11 Aug, 2020
Review #1 received
Received 11 Aug, 2020
Editor assigned
On 10 Aug, 2020
Reviewers invited
Invitations sent on 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
No comments provided
Editorial decision: Major revision
On 16 Jul, 2020
Review #1 received
Received 27 Jun, 2020
Review #2 received
Received 27 Jun, 2020
Reviewer #2 agreed
On 14 Jun, 2020
Reviewer #1 agreed
On 09 Jun, 2020
Reviewers invited
Invitations sent on 16 May, 2020
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Urology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Michael J Donovan
Icahn School of Medicine at Mt. Sinai
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0772-598X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Urology.
No community comments so far
Editorial decision: Accept
On 25 Aug, 2020
Editor assigned
On 21 Aug, 2020
Submission checks complete
On 20 Aug, 2020
Editor invited
On 20 Aug, 2020
Version 2
Posted 13 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 19 Aug, 2020
Review #2 received
Received 17 Aug, 2020
Reviewer #1 agreed
On 11 Aug, 2020
Reviewer #2 agreed
On 11 Aug, 2020
Review #1 received
Received 11 Aug, 2020
Editor assigned
On 10 Aug, 2020
Reviewers invited
Invitations sent on 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
No comments provided
Editorial decision: Major revision
On 16 Jul, 2020
Review #1 received
Received 27 Jun, 2020
Review #2 received
Received 27 Jun, 2020
Reviewer #2 agreed
On 14 Jun, 2020
Reviewer #1 agreed
On 09 Jun, 2020
Reviewers invited
Invitations sent on 16 May, 2020
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Urology & Nephrology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Urology.
BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.
Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.
Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.
Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.
Figure 1
This is a list of supplementary files associated with this preprint. Click to download.
Loading...