CUA 2017: Potential Role of a Novel Urinary Biomarker-Based Risk Score to Select Patients for Multiparametric Magnetic Resonance Imaging for Prostate Cancer Detection

Toronto, Ontario ( Introduction of multiparametric MRI (mpMRI) has drastically changed the landscape of prostate cancer (PCa) diagnostics. However, as with any diagnostic tool, learning to better select patients for appropriate use, especially in a cost-effective manner, is critically important. While originally touted to be an excellent discriminator between clinically significant prostate cancer and indolent disease, more recent results have been sobering; false negatives still persist in the range of 10-20%.

In this study, the authors aim to assess the utility of a novel biomarker-based risk score (SelectMDx), which utilizes urinary HOXC6 and DLXI mRNA expression levels combined with traditional clinical risk factors to high-grade PCa (Gleason score ≥7) at the time of prostate biopsy, to help better risk-stratify patients and reduce unnecessary biopsies. Importantly, the risk score improved upon the PCA3 test, by working well in men with a low PSA. It was demonstrated to have an AUC of 0.90!

To do so, they compared the SelectMDx risk score against mpMRI. The patients utilized in this retrospective observational cohort were previously included in the validation study of the SelectMDx risk score, in which urine was collected after digital rectal exam (DRE) from men undergoing prostate biopsies based on an elevated serum prostate-specific antigen (PSA) (≥3.0 ng/ml) and/or suspicious DRE. Specifically, they assessed a subset of patients who underwent a mpMRI after prostate biopsies were performed (n=174). The indications for MRI were based on persistent clinical suspicion of PCa after a negative prostate biopsy or staging after PCa was found upon biopsy.

Of the 174 patients, 102 (59%) had PCa detected upon biopsy, of which 54 (53%) had high-grade disease and a significantly higher SelectMDx risk score (p<0.001). 

When compared to mpMRI, the median SelectMDx risk score was significantly higher in patients who had a suspicious lesion on MRI (p<0.001). For 81 mpMRIs, the Prostate Imaging Reporting and Data System (PI-RADS) classification was reported and there was a positivie correlation observed between the risk score and the PI-RADS classification – specifically for PIRADS 4-5 lesions. A Kruskal-Wallis test indicated a statistically significant difference in SelectMDx risk scores between the different PI-RADS groups (p<0.001).

Based on this the authors suggest a correlation between SelectMDx scores and mpMRI findings. However, it is important to note that mpMRI does not always imply high-risk cancer. While the findings are suggestive, a more formal study sequenced as follows needs to be done: clinical suspicion of prostate cancer  SelectMDx and mpMRI  mpMRI targeted biopsy. In this way, a more accurate correlation to diagnosis of clinically significant prostate cancer can be made.

Limitations / Discussion Points:
1. Correlation to mpMRI findings alone do not necessarily imply PCa diagnosis.

2. This was not a standardized exam – they only used patients that got a mpMRI for some indication. Hence it was a selected population at risk for higher-risk disease due to clinical concern.

Further studies are clearly warranted. They have completed recruitment for a prospective study in the Dutch population, entitled the 4M trial. The results will be released later this year. 

Presented By: Jack Schalken, PhD, Radboud University Medical Center, Nijmegen, Netherlands

Co-Authors: Rianne J Hendriks, Marloes MG van der Leest, Peter FA Mulders, Inge MG van Oort

Institutions: Radboud University Medical Center, Nijmegen, Netherlands

Witten By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto  Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada