In a validation study with data presented at the American Urological Association’s 2021 Annual Meeting, clinician-researchers reported that a new test (miR Sentinel PCC4 Test) may be able to detect and risk-classify prostate cancer at the molecular level with predictive accuracy based on a single urine sample. The data were reported on September 12, 2021, in a late-breaking abstract presented by Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto. Dr. Klotz is also Chief Medical Officer of miR Scientific LLC, which funded the study (Abstract LBA02-09). This validation study follows and confirms the positive data on more than 1,400 patients published by Wang et al in The Journal of Urology in September 2020.
Laurence Klotz, MD, FRCSC
When compared with systematic core needle biopsy, results of the Sentinel (PCC4) Test validation study demonstrated a 93% concordance between the two methods of screening/detection regarding classification of clinically significant cancer. The accuracy of the classification of “not clinically significant” cancer was 96%.
Cross-Validation Study Shows High Sensitivity
For this cross-validation study, Dr. Klotz and colleagues recruited a total of 763 men older than age 45 years who were scheduled to undergo their first core needle biopsy. Patients with pathologic evidence of disease were classified into Gleason Grade Group 1 to 5. Using the assay, the researchers then isolated small noncoding RNAs from urinary exosomes and interrogated them by reverse transcription polymerase chain reaction to differentiate patients with no molecular evidence of prostate cancer from those with molecular evidence of prostate cancer. The test further classified men with molecular evidence of disease into low-risk, intermediate-risk, or high-risk categories.
Of the 763 patients who underwent systematic core needle biopsy, 364 (46%) were biopsy-negative. Of those found to have pathologic evidence of disease, 189 (25%) were classified as Grade Group 1 (GG1), 97 were classified as Grade Group 2 (GG2), and 123 were classified as Grade Group 3 or greater.
When compared with results of the PCC4 assay, Dr. Klotz reported a 93% concordance between the screening/detection methods; that is, 93% of the patients found to have clinically significant cancer based on biopsy were identified on the assay. The false-negative rate was 7%.
Results of the study also showed that only 4% of clinically significant cancers were misclassified as having no molecular evidence of prostate cancer using the assay. The negative predictive value for “not clinically significant cancer” was thus 96%.
New Technology Measures Noncoding RNA Molecules
In an interview with The ASCO Post, Dr. Klotz explained that the test’s novel screening/detection approach interrogates information from exosomes, the small, extracellular vesicles found in biologic fluids (including blood, semen, cerebrospinal fluid, and urine). The presence of exosomes in the tumor microenvironment has recently been linked to malignancy in several tumor types, including prostate and other urologic cancers, but has rarely been used in cancer diagnostics, he said.
This new technology measures the expressions of 442 small noncoding RNA molecules, which can be obtained from a urine sample and sorted with a gene-expression array. A proprietary algorithm is then used to detect and process signals from hundreds of different markers—irrespective of their individual function.
Although these noncoding RNAs may be functionally meaningless, said Dr. Klotz, when different signatures are compared across various endpoints—cancer vs no cancer or aggressive vs indolent disease, for example—meaningful patterns emerge.
Predictive Value: A Key Feature of the Test
“The key features of the test are the very high negative predictive value—it’s a negative test you can rely on—and the very high accuracy [in] identifying cancer,” said Dr. Klotz. “In addition to its rapid turnaround, the test is scalable: the company will be able to perform a very large number of these tests right away.”
The authors concluded that the assay appears to offer an accurate noninvasive means (eg, no prostate massage needed) to identify the presence or absence of any prostate cancer and predict pathologic grade on biopsy. “The [assay], which has a turnaround time of 4 days or fewer, provides high sensitivity for the presence or absence of any prostate cancer, low-risk vs intermediate- or high-risk disease, and intermediate- vs high-risk disease,” Dr. Klotz added. “I would say as a caveat, however, that further validation studies are ongoing.”
The FDA granted Breakthrough Device designation to the Sentinel Test in October 2020.
Disclosure: Dr. Klotz is Chief Medical Officer of miR Scientific LLC, which funded the study.
“Population-based screening for prostate cancer reduces prostate cancer mortality,” noted J. Kellogg Parsons, MD, MHS, FACS, Professor of Urology, UC San Diego Health, who commented on the study. “Effective screening programs focus on the early detection of aggressive but curable tumors, minimize...