One such biomarker that has been evaluated is the SelectMDx, a urine-based molecular test that has been clinically validated for the detection of high-grade PCa in European men.1 In that study, HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach (the mRNS signature and clinical markers together) reached an overall AUC of 0.90 (95% confidence interval [CI], 0.85-0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components. Analyses indicated a strong net benefit and significant reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay.
In this prospective study, the authors evaluated SelectMDx’ clinical performance in a cohort of U.S. men undergoing initial prostate biopsy in a community urology practice. The study population consisted of 330 prospectively enrolled men who were undergoing initial prostate biopsy at a large community urology practice due to suspected PCa (UroPartners, Chicago, IL). Post-DRE urine was collected from all subjects prior to biopsy, and samples shipped under ambient conditions to the testing laboratory (MDxHealth, Irvine, CA). Urinary HOXC6 and
DLX-1 mRNAs were quantified, and the RNA results combined in a clinical model with other risk factors to determine the likelihood that subsequent biopsy would identify ISUP grade group (GG) >= 2 (Gleason Score >= 7) cancer. They assessed SelectMDx performance characteristics for detection of GG2 and higher PCa in this cohort.
They enrolled 330 subjects who were biopsy-naïve. The average age was 57 years (median 63, interquartile range 54 to 68), and average serum PSA level 8.3 ng/mL (5.7, 4.5 to 8.1). Full demographics below:

In terms of biopsy results, cancer was identified in 148/330 (44.8%) men biopsied. Of these, 64/148 (43.2%) had Gleason grade group (GG1) disease, 47/148 (31.8%) had GG2, 7/148 (4.7%) GG3 and 30/148 (20.3%) had GG4-5. For detection of GG2+ vs. GG1 or no PCa at biopsy, SelectMDx sensitivity was 81% (95% C.I. 71-89%), specificity 46% (40-52%), negative predictive value (NPV) 88% (82-92%) and positive predictive value (PPV) 34% (31-37%). No AUC was provided.
In this cohort, 84/330 (25.5%) subjects were found to have GG2 or higher cancer. At an adjusted disease prevalence of 12% GG2-5 PCa, SelectMDx NPV and PPV were 95% and 18%,
respectively.
This study, in a community US practice, validated the findings of the prospective randomized European study. The high negative predictive value is particularly appealing.
Presented By: Paul Matthew Yonover, MD
Co-Authors: Sandra Steyaert, PhD; Celeste Ruiz, RN; Karolina Grafczynska, RN; Jessica DeHart; Michael Brawer, MD; Jack Schalken, MD, PhD; Jack Groskopf, PhD and Wim Wim Van Criekinge, PhD
Institution(s): UroPartners, Chicago, IL; 2 MDxHealth, Irvine, CA; 3 Radboud University Medical Center, Nijmegen, The Netherlands; 4 Ghent University, Ghent, Belgium
References:
Van Neste L et al. Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. Eur Urol. 2016 Nov;70(5):740-748. doi: 10.1016/j.eururo 2016.04.012. Epub 2016 Apr 20.
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @TjuUrology, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona