INSIGHT-PCa: MRI- and PHI-Guided Risk-Adapted Strategy for Prostate Cancer Diagnosis

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