Evaluation of an MRI-based Prostate Cancer Screening Program (VISIONING): 5-Year Follow-up Round (VISIONING III)

This study (VISIONING III) is a prospective, single-center, longitudinal cohort follow-up of the previously completed VISIONING I and II prostate cancer screening phases. It evaluates the long-term safety, diagnostic performance, and negative predictive value of a biparametric MRI (bpMRI)-based opportunistic screening strategy for prostate cancer over a five-year interval. The primary objective is to determine the five-year incidence of clinically significant prostate cancer (csPCa, defined as ISUP grade group ≥2) in men who previously underwent bpMRI-based screening and either: had a negative bpMRI without biopsy indication, had a negative biopsy result, or were diagnosed with low-risk prostate cancer and managed with active surveillance. The central hypothesis is that a negative bpMRI-based screening result provides durable protection against the development of clinically significant prostate cancer over at least five years, demonstrating a high negative predictive value. Additionally, it is hypothesized that systematic re-evaluation after five years will identify a clinically meaningful proportion of previously undetected csPCa in men who meet predefined biopsy criteria. VISIONING III is a prospective, observational, longitudinal cohort study conducted at a single tertiary referral center. It represents the structured five-year follow-up of participants from the VISIONING I/II screening cohorts. No experimental intervention is introduced; all diagnostic procedures follow predefined clinical criteria aligned with current European Association of Urology (EAU) guidelines. The study includes two key timepoints: Baseline: prior bpMRI-based screening (already completed in VISIONING I/II) Follow-up: structured reassessment at approximately five years (VISIONING III). At follow-up, all participants undergo repeat bpMRI and serum PSA testing, including PSA density (PSAD) calculation. Follow-Up Procedures: Participants are reassessed using a standardized protocol: Imaging and Laboratory Testing. Repeat biparametric MRI (bpMRI), classified using PI-RADS (1-5). Serum PSA measurement: PSA density calculation (PSA divided by MRI-derived prostate volume). Biopsy Indications: Biopsy is performed only if predefined criteria are met: PI-RADS ≥4 lesion on bpMRI, or PSA density ≥0.15 ng/ml², or PSA >10 ng/ml, or Persistent or upgraded PI-RADS 3 lesion after 6 months. For PI-RADS 3 lesions: Repeat multiparametric MRI after 6 months. Biopsy only if lesion persists or upgrades. Primary Endpoint: Five-year ISUP ≥2 diagnosis-free survival after initial negative screening round. This measures the proportion of participants remaining free of clinically significant prostate cancer five years after baseline screening. Secondary Endpoints: Treatment-free survival. Time to radical prostatectomy, radiotherapy, focal therapy, or death. Stratified by baseline screening category. Biopsy-free and re-MRI-free survival. Time to any prostate biopsy or repeat MRI after baseline screening. Includes death as censoring event. Diagnostic yield of repeat screening. Detection rates of clinically significant and clinically non-significant prostate cancer. Diagnostic efficiency metrics. Number of MRIs and biopsies needed to detect one csPCa case. Comparison with first screening round (VISIONING I/II). Longitudinal biomarker and imaging changes. Changes in PSA, PSA density, PI-RADS scores over five years. mPredictive value of these changes for csPCa detection. Oncological safety outcomes. Metastasis-free survival. Prostate cancer-specific survival. Morphological prostate changes. Prostate volume, transition zone volume, and structural changes. Association with PSA, age, and cancer outcomes. Outcomes after definitive treatment. Clinical outcomes in participants undergoing surgery, radiotherapy, or focal therapy during follow-up. Independent Variables. Key predictors include: Baseline screening status. MRI-negative without biopsy. MRI-negative with negative biopsy. Low-risk prostate cancer under active surveillance. Repeat bpMRI findings. PI-RADS score (1-5). Lesion size, location, progression. PSA-related measures. PSA level and PSA density at follow-up. PSA kinetics compared to baseline. Biopsy-related variables. Biopsy performed (yes/no). Histopathological outcome (ISUP grade group 1-5). Study Population. Participants are drawn from the original VISIONING I/II cohort. Inclusion is limited to men who previously underwent bpMRI-based screening and did not receive definitive treatment for prostate cancer after the initial screening round (except those on active surveillance for low-risk disease). Study Rationale: Prostate cancer screening using bpMRI as a first-line diagnostic tool has shown promise in reducing unnecessary biopsies while maintaining high detection rates for clinically significant disease. However, long-term data on the durability of a negative bpMRI result are limited. This study addresses this gap by evaluating five-year outcomes, including delayed detection of csPCa, treatment-free survival, and the long-term negative predictive value of bpMRI in a real-world opportunistic screening setting. Additional Considerations: Study is observational and non-interventional. Conducted at a single tertiary center.

Standardized imaging and biopsy criteria ensure internal consistency. No formal patient or public involvement in study design, though iterative improvements were informed by prior cohort feedback.

Participant burden was reduced by removing routine DRE and pre-biopsy questionnaires, based on prior phase experience. Expected Impact: The study aims to provide robust evidence on:

Long-term safety of bpMRI-first prostate cancer screening. Optimal follow-up strategies after negative MRI findings. Efficient use of MRI and biopsy in population-based opportunistic screening. Refinement of risk stratification using PSA, PSA density, and PI-RADS evolution

Inclusion criteria

• "well-informed men" with the wish for prostate cancer screening:
• prostate biopsy naïve
• life expectancy > 10 years
• Paticipant in the VISIONING study

Exclusion criteria

• prostate volume > 80ml
• acute urinary tract infection UTI
• NIH-CPSI score over or equal to19
• IPSS score over or equal to 20 (leads to initiation of urologic diagnostics and treatment)
• life expectancy < 10 years