Independent Evaluation of the Respective Predictive Values for High-Grade Prostate Cancer of Clinical Information and RNA Biomarkers after Upfront MRI and Image-Guided Biopsies.

Mathieu Roumiguié,Olivier Meyrignac,Eric Bruguière,Léonor Nogueira,Marine Lesourd,Sarah Péricart,Bernard Malavaud,Guillaume Ploussard

doi:10.3390/cancers12020285

Abstract

Upfront MRI is taking the lead in the diagnosis of clinically significant prostate cancer, while few image-guided biopsies (IGBs) fail to demonstrate clinically significant prostate cancer. The added value of innovative biomarkers is not confirmed in this context. We analysed SelectMDx-v2 (MDx-2) in a cohort of upfront MRI and image-guided biopsy patients. Participants included patients who received a trans-rectal elastic-fusion registration IGB on the basis of DRE, PSA, PCA3, and PCPT-2.0 risk evaluation. Pre-biopsy MRI DICOM archives were reviewed according to PI-RADS-v2. Post-massage first-void urine samples stored in the institutional registered bio-repository were commercially addressed to MDxHealth to obtain MDx-2 scores. Univariate and multivariate analyses were conducted with the detection on IGB of high-grade (ISUP 2 and higher) as the dependent variable. High-grade cancer was demonstrated in 32/117 (27.4%) patients (8/2010–8/2018). Age, prostate volume, biopsy history, MDx-2, and PI-RADS-v2 scores significantly related to the detection of high-grade cancer. MDx-2 scores and the clinical variables embedded into MDx-2 scores were analysed in multivariate analysis to complement PI-RADS-v2 scores. The two combinations outperformed PI-RADS-v2 alone (AUC-ROC 0.67 vs. 0.73 and 0.80, respectively, p < 0.05) and calibration curves confirmed an adequate prediction. Similar discrimination (C-statistics, p = 0.22) was observed in the prediction of high-grade cancer, thereby questioning the respective inputs and added values of biomarkers and clinical predictors in MDx-2 scores. Based on the results of this study, we can conclude that instruments of prediction developed for systematic prostate biopsies, including those that incorporate innovative biomarkers, must be reassessed and eventually confirmed in the context of upfront MRI and IGB.

Highlights

Current efforts in prostate cancer diagnosis follow a fine line between evidencing significant cancers that warrant intervention and controlling the overdiagnosis of insignificant lesions
MDx-2, which belongs to the latest generation of biomarker-based models of prediction, was selected for this study as it could be retrospectively tested from archived prostate massage samples
Washino recently observed that no PI-RADS-v2 score 3 lesions proved positive on transperineal systematic or cognitive biopsies when PSA density was lower than 0.15, suggesting that biology could help refine the risk estimation based on MRI [11]

Summary

Introduction

Current efforts in prostate cancer diagnosis follow a fine line between evidencing significant cancers that warrant intervention and controlling the overdiagnosis of insignificant lesions. A recent modelling of diagnostic avenues [1] based on the PROMIS cohort supported upfront MRI as a dominant strategy in biopsy-naive patients to inform the suspicion and location of putative lesions [2], it might substantially reorient medical resources and expenditures. To date, no efforts have been made to introduce predictive tools [3] or innovative biomarkers [4] in the process of selection, they have been heavily researched and promoted in the precedent strategy of clinically driven systematic ultrasound-guided biopsies. The highly competitive market of biomarker research has followed different avenues, such as PSA trafficking (Prostate Health Index, 4K score) and cancer-specific non-coding RNAs (PCA3) eventually combined with fusion genes (MIMPS), and has more recently acknowledged the added value of clinical information (SelectMDx-v2 (MDx-2), STHLM3) [5].

Methods

Discussion

Conclusion