Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro): Study protocol for a multicenter, multinational trial evaluating biparametric MRI and advanced, quantitative diffusion MRI for detection of prostate cancer

Background: Multiparametric MRI (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, major limitations of mpMRI are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric MRI (bpMRI) and advanced, quantitative MRI techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Purpose: To evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs, and to evaluate characteristics of RSIrs as a stand-alone, quantitative biomarker. Design, setting, and participants: ART-Pro is a multisite, multinational trial that will be conducted in two stages, evaluating bpMRI, mpMRI, and RSIrs on accuracy of expert (ART-Pro-1) and non-expert (ART-Pro-2) radiologists' detection of csPCa. Additionally, RSIrs will be evaluated as a stand-alone, quantitative, objective biomarker (ART-Pro-1). This study will include a total of 500 patients referred for a multiparametric prostate MRI with a clinical suspicion of prostate cancer at any of the five participating sites (100 patients per site). Intervention: In ART-Pro-1, patients receive standard of care mpMRI, with addition of the RSI sequence, and subsets of the patients' images are read separately by two expert radiologists, one of whom is the standard of care radiologist (Reader 1). Three research reports are generated using: bpMRI only (Reader 1), mpMRI (Reader 1), and bpMRI + RSIrs (Reader 2). The clinical report is submitted by Reader 1. Patients' future prostate cancer management will be recorded and used to evaluate the performance of the MRI techniques being tested. In ART-Pro-2, the dataset created in ART-Pro-1 will be retrospectively reviewed by radiologists of varying experience level (novice, basic, and expert). Radiologists will be assigned to read cases and record research reports while viewing subsets of either mpMRI only or RSIrs + mpMRI. Patient cases will be read by two readers from each experience level (6 reads total), and findings will be evaluated against the expertly created dataset from ART-Pro-1. Outcome measurements and statistical analysis: The primary endpoint is to evaluate if bpMRI is non-inferior to mpMRI among expert radiologists (ART-Pro-1) and non-expert radiologists (ART-Pro-2) for detection of grade group (GG) ≥2 csPCa. We will conduct one-sided non-inferiority tests of correlated proportions (ART-Pro-1) and use McNemar's test and AUC to test the null hypothesis of non-inferiority (ART-Pro-1 and ART-Pro-2). Conclusions: This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT06579417) at ClinicalTrials.gov. Patient accrual at the first site (UC San Diego) began in December 2023. The expected trial timeline is three years to complete accrual with a six-month endpoint.