Micro-UltraSound In Cancer – Active Surveillance (MUSIC-AS): A paired, prospective, non-inferiority trial comparing micro-ultrasound and multiparametric MRI at confirmatory biopsy

Background: Accurate risk assessment is essential for men on active surveillance (AS) of prostate cancer (PCa). Multiparametric MRI improves detection of clinically significant PCa (csPCa; Grade Group ≥2) but is limited by registration error, contraindications and long wait times. Micro-ultrasound (microUS) is a high-resolution, real-time imaging modality that has been shown to be non-inferior to MRI for the detection of csPCa in biopsy-naïve men. However, trials comparing microUS against MRI in men managed by AS remain limited. Methods: MUSIC-AS is a paired, within-subject, prospective non-inferiority diagnostic trial comparing microUS and MRI for the detection of csPCa in men undergoing confirmatory biopsy during AS. Eligible participants include men with previously diagnosed Grade Group 1 PCa requiring confirmatory biopsy. Each participant will undergo pre-biopsy MRI followed by a microUS/MRI-guided biopsy (in which the operator is initially blinded to the MRI during acquisition of microUS targeted cores) followed by MRI targeted cores and systematic sampling. The primary endpoint is the detection of csPCa by combined targeted plus systematic biopsies. The planned sample size is 210 participants. Results: The primary hypothesis is non-inferiority of the csPCa detection rate between microUS-targeted plus systematic biopsies and MRI-targeted plus systematic biopsies. Secondary analyses will evaluate upgrade-free probabilities at 2, 5, and 10 years after confirmatory biopsy. An exploratory analysis using germline sequencing will be performed. Conclusions: MUSIC-AS will determine whether micro-ultrasound is non-inferior to MRI for detecting csPCa in men on active surveillance. Confirmation of non-inferiority may support microUS as a cost-effective, time-efficient, and widely accessible imaging alternative in this population.