PD11-11: A urinary exosome assay interrogating small non-coding RNAs accurately identifies and stratifies prostate cancer into low- intermediate- or high-risk disease.

Laurence Klotz*, Toronto, Canada, Winnie Wang, Rensselaer, NY, Alvin Lopez Pujals, Caguas, Puerto Rico, Deepak Kapoor, New Hyde Park, NY, Rebecca DeVaux, Greg DiRienzo, Rensselaer, NY, Federico Corica, Ann Anderson, San Juan, Puerto Rico, Carl Olsson, New Hyde Park, NY, Alberto Corica, San Juan, Puerto Rico, James Libby, Stockbridge , GA, Martin Tenniswood, Rensselaer, NY

Introduction: The miR Sentinel®  Test measures the expression of 442 small non-coding RNAs (sncRNAs) extracted from urinary exosomes to differentiate patients with No Molecular Evidence of Prostate Cancer (NMEPCa) from those with Molecular Evidence of Prostate Cancer (MEPCa). The test further classifies men with MEPCa into low-, intermediate- or high-risk disease. We compared the results of the miR Sentinel® PCC4 Test to systematic and MRI-guided core needle biopsy in men at risk for  prostate cancer.

Methods: 763 biopsy naïve men  in whom a prostate biopsy was indicated, were recruited.   sncRNAs were isolated from urinary exosomes and interrogated by RT-qPCR on a custom designed OpenArray platform.

Results: The validation cohort consisted of 763 biopsy naïve patients undergoing systematic or systematic plus targeted biopsy.  The molecular classification was compared to the Gleason Grade Group (GG) (Table 1). Sensitivity for the classification of {NPEPC or GG1} versus {GG2-5} was 75+18+4+105=203)/221 = 92.2% and the negative predictive value for absence of CS PCa was  (221+64+12+123=420)/(238+200=420)= 96%.  The apparent false positive rate for CS cancer was (34+35+32+22=(123)/(543) = 23%.   208 of the patients had discordant systematic and targeted biopsies.   29 of these had a  negative systematic biopsy and  a positive targeted biopsy.  The molecular test predicted the targeted biopsy outcome in 27/29= 93.1% overall, and in  14/15 (93%) of the cases with clinically significant cancer.   In the 18 patients with positive  systematic and negative MRI targeted biopsies, the test result predicted the positive biopsy in  100%.

Pathology-based

Classification

Systematic/MRI guided biopsy

Total Participants

Sentinel Risk Classification

Frequency Counts

NMEPCa

LOW

INTERMEDIATE

HIGH

NPEPCa

354

543

221

64

34

35

GG1

189

12

123

32

22

GG2

97

220

0

4 (2%)

75

18

GG3-GG5

123

5 (2.1%)

9 (4.5%)

4

105

TOTAL

763

238

200

145

180

Table 1.  Sentinel Test  cross-validation study versus Grade Group

Conclusions: The miR Sentinel Test offers an accurate non-invasive means to accurately identify the presence or absence of prostate cancer and classify risk status predict pathological grade on biopsy.  The high predictive accuracy of the test in patients whose systematic and targeted biopsy were discordant suggests  that the 23% discordance between negative biopsy results and  positive Sentinel Test results was in most cases due to  false negative biopsies.

Source of Funding: The study was funded by miR Scientific