This prospective randomized controlled trial aims to compare transperineal and transrectal cognitive fusion prostate biopsy techniques in patients with suspicious prostate lesions detected by multiparametric magnetic resonance imaging (mpMRI).

Patients aged 50-75 years with PI-RADS 3-5 lesions on mpMRI and an indication for prostate biopsy will be randomly assigned in a 1:1 ratio to undergo either transperineal cognitive fusion prostate biopsy or transrectal cognitive fusion prostate biopsy.

The primary objective of this study is to evaluate whether transperineal cognitive fusion biopsy is non-inferior to transrectal cognitive fusion biopsy in detecting clinically significant prostate cancer (csPCa). Secondary objectives include comparison of overall prostate cancer detection rates, detection of Gleason Grade Group ≥2 prostate cancer, biopsy-related infectious complications, other procedure-related complications, pain scores, and procedure duration.

A total of 280 participants will be enrolled. Pathological evaluation will be performed after biopsy, and clinical outcomes and complications will be assessed during follow-up.

Prostate cancer is one of the most common malignancies among men. Multiparametric magnetic resonance imaging (mpMRI) has become an important tool for prostate cancer detection and risk stratification, particularly with the use of the Prostate Imaging Reporting and Data System (PI-RADS). Patients with PI-RADS 3-5 lesions are frequently considered candidates for targeted prostate biopsy.

Transrectal ultrasound-guided prostate biopsy has traditionally been the standard biopsy approach. However, the transrectal route may carry a risk of infectious complications due to passage through rectal mucosa and exposure to rectal flora. Transperineal prostate biopsy has gained increasing interest because it avoids transgression of the rectal mucosa and may reduce infectious complications.

Cognitive fusion biopsy is an MRI-targeted biopsy technique in which mpMRI findings are mentally correlated with real-time ultrasound images by the operator. This technique provides an accessible alternative to software-based fusion systems and can achieve accurate targeted sampling when performed by experienced clinicians.

The aim of this study is to prospectively compare transperineal and transrectal cognitive fusion prostate biopsy techniques regarding diagnostic performance and safety outcomes in patients with PI-RADS 3-5 lesions detected on mpMRI.

Eligible participants aged 50-75 years with biopsy indications will be randomized using a computer-generated stratified block randomization method. Randomization will be stratified according to PI-RADS category (3, 4, or 5) and age group (<60 years and ≥60 years).

Participants will undergo either transperineal or transrectal cognitive fusion prostate biopsy according to their assigned study group. Systematic biopsy cores and targeted biopsy cores will be obtained according to the institutional protocol.

The primary endpoint is the detection rate of clinically significant prostate cancer, defined as Gleason Grade Group ≥2 (ISUP Grade Group ≥2) prostate cancer. The primary analysis will evaluate non-inferiority of transperineal biopsy compared with transrectal biopsy.

Secondary endpoints include overall prostate cancer detection rate, Gleason Grade Group ≥2 cancer detection, infectious complications (fever, urinary infection, prostatitis, sepsis), procedure-related complications (hematuria, hematospermia, urinary retention), pain assessed by visual analog scale (VAS), and procedure duration.

Participants will be followed for 30 days after biopsy for assessment of adverse events and complications.

Inclusion Criteria:

• Male patients aged 50-75 years.
• Patients with PI-RADS 3, 4, or 5 lesions detected on multiparametric prostate magnetic resonance imaging (mpMRI).
• Patients with an indication for prostate biopsy.
• Patients who are willing to participate and provide informed consent.

Exclusion Criteria:

• Previous diagnosis of prostate cancer.
• Active urinary tract infection.
• Coagulopathy or bleeding disorders preventing prostate biopsy.
• Absence of multiparametric prostate MRI evaluation.
• No indication for prostate biopsy.

Pathologists evaluating biopsy specimens will be blinded to the biopsy technique. Participants, care providers, and investigators performing the biopsy procedure will not be blinded due to the nature of the intervention.