Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial.

Ivan Jambor ,Harri Merisaari ,Tommi Kauko ,Jani Saunavaara ,Aida Kiviniemi ,Sanna Mari Vimpeli ,Kari Syvänen ,Ileana Montoya Perez ,Juha Knaapila ,Tuomas Mirtti ,Esa Kähkönen ,Outi Oksanen ,Tarja Lamminen ,Marjo Seppänen ,Jarno Riikonen ,Markku Kallajoki ,Hannu J Aronen ,Antti Rannikko ,Janne Verho ,Otto Ettala ,Pekka Taimen ,Peter J Boström

doi:10.1371/journal.pmed.1002813

Abstract

BackgroundMagnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption.Methods and findingsThe aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3–5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1–2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy—including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value—of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%–98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings.ConclusionsIMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.Trial registrationClinicalTrials.gov NCT02241122.

Highlights

Prostate cancer (PCa) is the most common solid organ cancer in men in Europe [1]
IMPROD biparametric magnetic resonance imaging (MRI) (bpMRI) demonstrated a high negative predictive value (NPV) for significant PCa (SPCa) in men with a clinical suspicion of prostate cancer (PCa) in this prospective multi-institutional clinical trial
The standard diagnostic pathway has relied on prostate specific antigen (PSA) levels and digital rectal examination (DRE) findings to determine if a man should undergo transrectal ultrasound-guided (TRUS) biopsies [2]

Summary

Introduction

Prostate cancer (PCa) is the most common solid organ cancer in men in Europe [1]. In contrast to the detection protocol for many other solid organ cancers, the decision of whom to biopsy among patients with a clinical suspicion of PCa has historically not been based on imaging findings [2]. The standard diagnostic pathway has relied on prostate specific antigen (PSA) levels and digital rectal examination (DRE) findings to determine if a man should undergo transrectal ultrasound-guided (TRUS) biopsies [2] This pathway is well known to result in unnecessary biopsies, overdetection of nonsignificant PCa (non-SPCa), and underdetection of clinically significant PCa (SPCa) [2]. Two recent prospective trials have shown that an alternative pathway using multiparametric magnetic resonance imaging (MRI) with dynamic contrast enhancement as a triage test reduces unnecessary biopsies, decreases the detection of non-SPCa, and improves the detection of SPCa [2,3]. Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption

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