PRIMA: randomized prospective multicenter non-inferiority study for primary diagnosis of clinically significant PRostate cancer by PSA and MR IMAging—study protocol for a randomized diagnostic accuracy trial

BACKGROUND: Diagnostic pathways based on PSA, digital rectal examination (DRE), and systematic biopsy (SB) may miss clinically significant prostate cancer (csPCa) and lead to overdiagnosis of indolent disease. Multiparametric MRI (mpMRI) and MRI-targeted biopsy (TB) improve detection of csPCa; however, the additional diagnostic value of routine SB in biopsy-naïve men with suspicious MRI findings remains controversial. METHODS: PRIMA is a randomized, prospective, multicenter non-inferiority diagnostic accuracy trial in eight German hospitals. Biopsy-naïve men aged 50-75 years with PSA ≥ 3 ng/ml and/or suspicious DRE undergo mpMRI (PI-RADS v2.1, PI-QUAL v2). Men with PI-RADS 4-5 or PI-RADS 3 with PSA density > 0.15 are randomized 1:1 to TB only (Arm A) or TB + SB (Arm B). Persistent PI-RADS 4-5 lesions with negative biopsy undergo MRI in-bore biopsy. OUTCOMES: Co-primary endpoints are csPCa (ISUP ≥ 2) detection and detection of clinically insignificant cancer (ISUP 1). Secondary endpoints include patient-reported outcomes (EORTC-QLQ-C30, EPIC-26, VAS), biopsy-related complications, biopsy approach, MRI in-bore yield, AI/radiomics validation and follow-up cancer incidence. SAMPLE SIZE: One thousand nine hundred eight men were allocated to achieve 1590 analyzable patients (> 80% power; non-inferiority margin δ = 13%). DISCUSSION: PRIMA will provide high-level evidence whether systematic biopsy can be safely omitted in MRI-positive biopsy-naïve men, potentially reducing diagnostic morbidity and overtreatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04993508. Registered on 2 December 2022.