Prostate Cancer
Conditions
Keywords
Urinary Exosome, ExoDx Prostate test, ExosomeDx, ERG, Erythroblast Transformation-Specific Related Gene, SPDEF, SAM Pointed Domain-containing ETS Transcription Factor, Exosome Diagnostic Intelligence, EPI, Prostate cancer, Prostate Biopsy, Exosome, Prostate MRI
Brief summary
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.
Interventions
DEVICEUrinary ExoDx test
A urine sample for ExoDx Study Kit will be collected onsite and shipped to Exosome Diagnostic's laboratory.
DIAGNOSTIC_TESTTransrectal ultrasound-guided prostate biopsy
Participants will be scheduled for transrectal ultrasound-guided prostate biopsy as per the standard diagnostic practice after urinary test.
DIAGNOSTIC_TESTTransperineal 12-core prostate biopsy
Participants will be scheduled for transperineal 12-core prostate biopsy as per the standard diagnostic practice after urinary test.
Sponsors
Bio-Techne Corporation
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
A prospective diagnostic test design will be used to compare the sensitivity of ExoDx with PSA density (H0: SensitivityPSA Density ≤ SensitivityExoDx versus H1: SensitivityPSA Density \> SensitivityExoDx) and the specificity (H0: Specificity PSA Density ≤ Specificity ExoDxversus H1: Specificity PSA Density \> Specificity ExoDx).
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | duration of study, average 3 months | 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 |
| Specificity | duration of study, average 3 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biopsy aversion rate | duration of study, average 3 months | 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. |
| Net Benefit | duration of study, average 3 months | 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. |
| Cancer Detection Rate | duration of study, average 3 months | 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 |
| Positive Predictive Value (PPV) | duration of study, average 3 months | Positive predictive value is defined as the probability that an elevated ExoDx actually has cancer. Positive Predictive Value = (True Positive)/(True Positive + False Positive) |
| Negative Predictive Value (NPV) | duration of study, average 3 months | Negative predictive value is defined as the probability a negative ExoDx test does not cancer. Negative Predictive Value = (True Negative)/(True Negative + False Negative) |
| Diagnostic Accuracy | duration of study, average 3 months | 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 |
| csPCa Detection Rate | duration of study, average 3 months | 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 |
Countries
United States
Contacts
Primary ContactNikhil Waingankar, MD
Outcome results
None listed