ExosomeDx in MRI-negative Men With High PSA

Evaluation of Urinary Exosomes as a Risk Stratification Tool Among Men With Elevated PSAs and Negative Prostate MRIs

Magnetic resonance imaging (MRI) has become the current standard of care in risk stratifying men with an elevated Prostate-specific antigen (PSA) to determine who needs to undergo prostate biopsy, which is invasive and carries a 3-5% risk of serious infection. Recent data shows the negative predictive value of MRI to be only 77%, indicating that some men may inappropriately forego biopsy based on a negative MRI. Urinary exosomes can be captured and analyzed by the ExosomeDx (ExoDx) Prostate test, a urine based, gene signature derived from PCA3 (prostate cancer antigen 3) and ERG (erythroblast transformation-specific related gene), and SPDEF (SAM pointed domain-containing ETS transcription factor); ExoDx carries a 90% negative predictive value.

The use of ExoDx test among patients with negative MRIs has the potential to improve the risk stratification of patients with an elevated PSA in a way that the Urologist can more accurately determine which patients need to undergo prostate biopsy. In doing so, the Urologist can better risk-stratify which patients should undergo prostate biopsy and be exposed to the associated potential risks, and also be more confident about the safety of foregoing biopsy in those patients with negative MRI and negative ExoDx test.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Device: Urinary ExoDx test; Diagnostic test: Transrectal ultrasound-guided prostate biopsy; Diagnostic test: Transperineal 12-core prostate biopsy

• Study Type: Interventional
• Enrollment (Estimated): 425
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nikhil Waingankar, MD; Phone Number: (718) 808-7777; Email: nikhil.waingankar@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10019
      • Mount Sinai West
      • Sub-Investigator: Craig Nobert
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
      • Contact: Nikhil Waingankar, MD; Phone Number: 718-808-7777; Email: nikhil.waingankar@mountsinai.org
      • Principal Investigator: Nikhil Waigankar
    • New York, New York, United States, 10025
      • Mount Sinai Morningside
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel / Union Square
      • Sub-Investigator: Michael Palese
    • New York, New York, United States, 11102
      • Mount Sinai Queens
      • Sub-Investigator: Nikhil Waigankar
    • New York, New York, United States, 11234
      • Mount Sinai Brooklyn
      • Principal Investigator: Nikhil Waigankar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all the following criteria;

• Willingness to participate and provide signed and dated informed consent form
• Male (sex)
• Age ≥ 18 years

• PSA screen-eligible, per investigator discretion

  • 45-75 years of age for average risk
  • 40-75 years of age for high risk
• PSA ≥ 2.0 ng/mL and ≤ 10.0 ng/mL
• MRI PIRADS score of 1 or 2
• ECOG 0-1
• Must have a negative urine culture prior to biopsy
• No prior prostate biopsies within the last 5 years (biopsy-naïve)
• Willingness to undergo a prostate biopsy as part of the diagnostic work-up
• Digital rectal exam with no palpable nodules

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study;

• Prior or current histologic or pathologic confirmed diagnosis of prostate cancer
• Prior transrectal ultrasound within the last 5 years
• Any prior cancer diagnosis within the last 5 years
• On immunosuppression or predefined immunosuppressed state
• A known coagulopathy predisposition to bleeding
• Diagnoses of any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
• Cognitive inability or psychiatric conditions that preclude informed decision making or compliance with study requirements (per investigator discretion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants with elevated or rising PSA; Participants who have been diagnosed with an elevated or rising PSA as determined by their urologist, and who have a negative (PIRADS 1 or 2) prostate MRI will be offered enrollment in this trial. ExoDx Study Kit will be collected onsite. Participants will then be scheduled for transrectal ultrasound-guided or transperineal 12-core prostate biopsy as per the standard diagnostic practice.

Device: Urinary ExoDx test; A urine sample for ExoDx Study Kit will be collected onsite and shipped to Exosome Diagnostic's laboratory.; Diagnostic test: Transrectal ultrasound-guided prostate biopsy; Participants will be scheduled for transrectal ultrasound-guided prostate biopsy as per the standard diagnostic practice after urinary test.; Diagnostic test: Transperineal 12-core prostate biopsy; Participants will be scheduled for transperineal 12-core prostate biopsy as per the standard diagnostic practice after urinary test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	Sensitivity is defined as the probability that clinically significant cancer is detected when it is cancer. Sensitivity = true positive cases / true positive cases + false negative cases	duration of study, average 3 months
Specificity	Specificity is defined as the probability that clinically significant cancer is not detected when it is not cancer. Specificity = true negative cases / true negative cases + false positive cases	duration of study, average 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Detection Rate	Cancer Detection Rate (CDR): Cancer detection rate is defined as the proportion of enrolled patients with histologically Gleason grade group 1+ cancers and as determined by the Investigator. Cancer detection rate = true positive (histologically Gleason grade 1+) / all tests performed	duration of study, average 3 months
csPCa Detection Rate	csPCa Detection Rate (csCDR): clinically significant cancer detection rate is defined as the proportion of enrolled patients with histologically Gleason grade group 2+ cancers. csPCa detection rate = true positive (histologically Gleason grade 2+) / all tests performed	duration of study, average 3 months
Biopsy aversion rate	Biopsy aversion rate is defined as the proportion of patients in whom the biopsy could have been potentially averted using ExosomeDx, as compared to decisions based on PSA density.	duration of study, average 3 months
Net Benefit	Decision curve analysis will be used to calculate the net benefit of adding ExoDx to PSA density (including kinetics and density) and MRI in the diagnostic workflow following. Net benefit is calculated across a range of threshold probabilities, defined as the minimum probability of disease at which further intervention would be warranted, as net benefit = sensitivity × prevalence - (1 - specificity) × (1 - prevalence) × w where w is the odds at the threshold probability.	duration of study, average 3 months
Diagnostic Accuracy	Accuracy is defined as the potential of ExoDx to correctly detect the presences or absence of disease. Diagnostic Accuracy = (True Positive) + True Negative / All) * 100	duration of study, average 3 months
Positive Predictive Value (PPV)	Positive predictive value is defined as the probability that an elevated ExoDx actually has cancer. Positive Predictive Value = (True Positive)/(True Positive + False Positive)	duration of study, average 3 months
Negative Predictive Value (NPV)	Negative predictive value is defined as the probability a negative ExoDx test does not cancer. Negative Predictive Value = (True Negative)/(True Negative + False Negative)	duration of study, average 3 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Bio-Techne Corporation
• Investigators: Principal Investigator: Nikhil Waingankar, MD, ICAHN School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 2, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Prostate cancer; Prostate Biopsy; Exosome; EPI; ERG; Prostate MRI; Urinary Exosome; ExoDx Prostate test; ExosomeDx; Erythroblast Transformation-Specific Related Gene; SPDEF; SAM Pointed Domain-containing ETS Transcription Factor; Exosome Diagnostic Intelligence
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: STUDY-24-00010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Specify Other Mechanism Email proposal to Principal Investigator.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes