Prostate cancer diagnosis based on systematic or MRI-targeted biopsy is associated with substantial overdiagnosis and unnecessary invasive procedures. Although multiparametric MRI improves detection of clinically significant prostate cancer, optimal criteria for biopsy omission-particularly in men with equivocal MRI findings-remain uncertain.

The INSIGHT-PCa study is a prospective, multicenter, randomized controlled trial designed to evaluate whether a risk-adapted diagnostic strategy integrating multiparametric MRI and the Prostate Health Index (PHI) can reduce unnecessary prostate biopsies without compromising detection of clinically significant prostate cancer.

Participants with suspected prostate cancer will be randomized to either a standard MRI-based diagnostic pathway or an optimized strategy in which biopsy decisions are guided by combined MRI findings and PHI density. The primary objective is to demonstrate non-inferiority in the detection of clinically significant prostate cancer while reducing biopsy utilization and biopsy-related adverse events.

This multicenter, prospective, randomized controlled trial will enroll 1,432 biopsy-naïve men with suspected prostate cancer across five tertiary referral centers in Korea. Eligible participants will have a serum prostate-specific antigen (PSA) level between 3 and 20 ng/mL.

Participants will be randomized in a 1:1 ratio to either a control group receiving a standard MRI-based diagnostic pathway or an experimental group managed using an optimized, risk-adapted strategy integrating multiparametric MRI and the Prostate Health Index.

In the control group, men with PI-RADS scores of 1-2 will undergo systematic 12-core transrectal ultrasound-guided biopsy, while those with PI-RADS scores of 3-5 will receive combined MRI-targeted and systematic biopsy.

In the experimental group, men with PI-RADS scores of 1-3 will undergo biopsy only if the PHI density is ≥0.80; biopsy will be omitted in those with lower PHI density and replaced by active surveillance. Men with PI-RADS scores of 4-5 will undergo MRI-targeted biopsy alone.

The trial is designed as a non-inferiority study. The primary endpoint is the proportion of clinically significant prostate cancer (Gleason score ≥3+4). Secondary endpoints include detection of clinically insignificant cancer, biopsy omission rates, biopsy-related adverse events, and cumulative detection of clinically significant prostate cancer during 24 months of follow-up.

Inclusion Criteria:

• Male, aged 20 years or older
• Serum PSA ≥3.0 ng/mL and ≤20.0 ng/mL and/or abnormal digital rectal -examination
• Biopsy-naïve
• Clinical stage ≤T2 disease
• Ability to provide written informed consent

Exclusion Criteria:

• Previous prostate biopsy or prostate cancer treatment
• Use of 5-alpha reductase inhibitors within 6 months
• Acute prostatitis or urinary tract infection within 3 months
• Contraindications to MRI
• Contraindications to prostate biopsy