AUA 2021: A High Through-Put Test Interrogating 442 Small Non-Coding RNAs Extracted from Urine Exosomes Accurately Identifies and Stratifies Prostate Cancer into Low-, Intermediate- or High-Risk Disease 

(UroToday.com) The American Urologic Association (AUA) annual meeting included a late-breaking abstract session with a presentation by Dr. Laurence Klotz discussing results of the Sentinel® Prostate Cancer Platform, a test for stratification of prostate cancer risk groups. The miR Sentinel® PCC4 Test measures the expressions of 442 small non-coding RNAs extracted from urinary exosomes to differentiate patients with no molecular evidence of prostate cancer from those with molecular evidence of prostate cancer. The test further classifies men with molecular evidence of prostate cancer into low-, intermediate- or high-risk disease. At the AUA meeting, Dr. Klotz and colleagues presented the results of their study comparing the miR Sentinel® PCC4 Test to systematic core needle biopsy in men presenting with initial suspicion of prostate cancer.


A total of 444 men over 45 years of age, scheduled for their first core needle biopsy, were recruited to the study. Small non-coding RNAs were isolated from urinary exosomes and interrogated by RT-PCR on a custom-designed OpenArray platform to provide the molecular classifications of “no molecular evidence of prostate cancer” or low- (corresponds to Gleason Group 1), intermediate- (corresponds to Gleason Group 2) or high-risk prostate cancer (corresponds to Gleason Group 3-5). The expression data for each patient is analyzed using a rigorously derived proprietary statistical classification system that operates using a discrete hazards modeling framework. As follows is the discrete hazard modeling approach:

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The molecular classification was compared to the Gleason Grade Group. Sensitivity and specificity for the classification of no molecular evidence of prostate cancer or Gleason Group 1 versus Gleason Group 2-5 was 130/132=98% and 300/312=96%, respectively. The concordance between the two methods was 413/444=93%. The false-negatives of the miR Sentinel® PCC4 Test are the lower-left discordances (5/444 = 1%), whereas the apparent false-positives correspond to the upper-right discordances (26/444 =6%).  The term ‘apparent’ alludes to the known false negative rate of systematic biopsy for significant cancer, which may account for some of the false positive test results.   Negative and positive predictive values of the miR Sentinel® PCC4 Test for no molecular evidence of prostate cancer versus molecular evidence of prostate cancer were 97% (164/169) and 92% (253/275), respectively.

 Among 108 men with negative systemic biopsies undergoing MRI targeted biopsies, 73% of both systematic and targeted biopsies were negative, and 27% were discordant with systematic biopsy negative, but targeted biopsy positive. Interestingly, in 100% of the discordant cases, the miR Sentinel® PCC4 Test was concordant with the targeted biopsy result, and 100% of the cases of Gleason Group >=2 prostate cancer (n=15) on targeted biopsy were predicted by the miR Sentinel® PCC4 Test. Finally, 10 of the 14 MRI positive Gleason Group 1 patients on targeted biopsy were molecularly risk classified as intermediate-high risk classification.

Dr. Klotz concluded his presentation of the miR Sentinel® PCC4 Test with the following take-home messages:

  • The miR Sentinel® PCC4 Test is a non-invasive molecular test based on the analysis of small non-coding RNAs isolated from non-DRE urinary exosomes
  • This test provided high sensitivity for the presence or absence of any cancer, low risk versus intermediate or high-risk disease, and intermediate versus high risk disease
  • The corresponding negative predictive values are high
  • The miR Sentinel® PCC4 Test has a rapid turnaround time of 65-96 hours and is readily scalable
  • Additional validations studies, required for FDA-PMA approval, are currently underway 

Presented by: Laurence Klotz, MD, FRCSC, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Co-Authors: Carl Olsson, Deepak Kapoor, Ann Anderson, Frederico Corica, Alberto Corica, James Libby, Martin Tenniswood, Rebecca Devaux, Greg DiRienzo, Winnie Wang

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.

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