Presentation Authors: Yashar Niknafs*, Jeffrey Tosoian, Scott Tomlins, Todd Morgan, Arul Chinnaiyan, Ann Arbor, MI
Introduction: Current prostate cancer detection methods are limited by their ability to predict disease progression, hence; new biomarker tests are of clinical utility. Tools to enhance clinical decision-making for patients with elevated PSA are limited. The PCPT risk calculator has been shown to be useful in this setting, but its efficacy is limited. Urine provides an excellent source to non-invasively detect biomarkers. We have developed a urine detection assay, quantitating the RNA-expression levels of the T2-ERG fusion and the lncRNA PCA3 in post-DRE urine samples. This test has potential to significantly enhance prognostication of patient outcomes for those with elevated PSA (particularly for identifying Gleason 7+ disease).
Methods: Urine samples were collected following-DRE from 15 institutions, and quantitation of KLK3, T2-ERG and PCA3 was performed on urine samples from over 1936 samples. In order to generate a model for prognostication, levels of PCA3 and T2-ERG were normalized to KLK3. We downloaded, curated, and processed 23,623 RNA-seq samples largely from the TCGA, ICGC, GTEx, and CCLE, comprising 37 tissue types and over 35 cancer types. These data were leveraged to identify a panel of genes with expression patterns that are highly specific to prostate tissue, and to prostate cancer. Additionally, data from diagnostic MRI was collected for 490 of these samples
Results: The urine biomarker panel was able to significant identify Gleason 7+ disease, with improved prognostic capacity over PSA with an AUC=0.76. Negative predictive value of the test was significant. If a risk score of 25% was used as a cutoff used to opt out of biopsy, 30% of negative biopsies could have been prevented, with a false negative rate of 5%. In our cohort, 33% of diagnostic MRIs with PI-RADS 3-5 were followed by negative biopsy or detection of Gleason 6 disease. The urine biomarker test was shown to predict low risk in these false negative MRI patients.
Conclusions: The strong negative predictive value of the urine biomarker test suggests clinical utility in enhancing decision to perform MRI or biopsy in patients with elevated PSA. Overall this test is capable of preventing many unnecessary biopsies, which benefits both patient morbidity and clinical cost.
Source of Funding: Prostate Cancer Foundation Young Investigator Award