SUO 2018: Prospective Clinical Validation of a Molecular Urine Test For Detection Of High-grade Prostate Cancer

Phoenix, Arizona ( As our knowledge of prostate cancer (PCa) continues to grow, we have increasingly come to accept the fact that there is a subset of PCa that has little long-term clinical implications and can be watched – clinically insignificant prostate cancer, often Gleason 6 PCa (Gleason Grade Group 1). However, some Gleason Grade Group 2 cancers may also fit the bill. The rest of the PCa, as far as our current knowledge enables us to know, is clinically significant (csPCa) warranting treatment. Currently, our ability to discriminate is limited to prostate biopsy and histopathology, though genomic markers are helping to discriminate csPCa from insignificant disease. As of yet, though, no biomarkers have been approved to determine eligibility for active surveillance (AS).

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:

Figure 1

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%,

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


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