Ipsilateral Versus Bilateral Systematic Biopsy Combined With MRI/Ultrasound Cognitive Fusion Targeted Biopsy for Prostate Cancer Diagnosis

• MRI/US Cognitive Fusion Targeted Biopsy Plus Ipsilateral Systematic Biopsy (Procedure): Transperineal MRI/ultrasound cognitive fusion targeted biopsy will be performed for all PI-RADS 3 or higher lesions on the MRI lesion side, with 3 cores obtained from each lesion. This will be followed by a 6-core systematic biopsy limited to the MRI lesion side, sampling the medial and lateral regions of the base, midgland, and apex. Local anesthesia will be limited to the MRI lesion side.
• MRI/US Cognitive Fusion Targeted Biopsy Plus Bilateral Systematic Biopsy (Procedure): Transperineal MRI/ultrasound cognitive fusion targeted biopsy will be performed for all PI-RADS 3 or higher lesions on the MRI lesion side, with 3 cores obtained from each lesion. This will be followed by a standard 12-core bilateral systematic biopsy sampling the medial and lateral regions of the base, midgland, and apex on both sides of the prostate. Bilateral local anesthesia will be administered.

Primary outcomes

• Detection Rate of Clinically Significant Prostate Cancer [Day 14 after biopsy]: The proportion of participants with clinically significant prostate cancer detected by the assigned biopsy strategy. Clinically significant prostate cancer is defined as biopsy pathology showing International Society of Urological Pathology (ISUP) Grade Group 2 or higher. The between-group risk difference will be calculated as TB+iSB minus TB+SB. Noninferiority will be concluded if the lower bound of the two-sided 95% confidence interval is greater than -15%.

Secondary outcomes

• Overall Prostate Cancer Detection Rate [Day 14 after biopsy]: The proportion of participants with prostate cancer detected on any biopsy specimen, regardless of ISUP Grade Group.
• Clinically Insignificant Prostate Cancer Detection Rate [Day 14 after biopsy]: The proportion of participants with biopsy pathology showing ISUP Grade Group 1 prostate cancer and no lesion with ISUP Grade Group 2 or higher.
• High-Grade Prostate Cancer Detection Rate [Day 14 after biopsy]: The proportion of participants with biopsy pathology showing ISUP Grade Group 3 or higher.
• Pain Numeric Rating Scale Score [Within 30 minutes after biopsy and at 24 hours after biopsy; additionally at day 7 (±2 days) among participants with persistent pain]: Biopsy-related pain associated with local anesthesia, needle puncture, and biopsy core acquisition will be assessed using an 11-point Numeric Rating Scale ranging from 0 to 10. A score of 0 indicates no pain and a score of 10 indicates the worst imaginable pain. Higher scores indicate greater pain.
• Overall Discomfort Numeric Rating Scale Score [Within 30 minutes after biopsy and at 24 hours after biopsy; additionally at day 7 (±2 days) among participants with persistent discomfort]: Overall procedural discomfort related to instrument insertion, ultrasound positioning or pressure, prostatic pressure, pelvic floor traction, foreign-body sensation, positioning, and the biopsy procedure will be assessed using an 11-point Numeric Rating Scale ranging from 0 to 10. A score of 0 indicates no discomfort and a score of 10 indicates the worst imaginable discomfort. Higher scores indicate greater discomfort.
• Procedure Time [During the biopsy procedure]: Procedure time in minutes, measured from the start of local anesthesia to completion of the final biopsy core. For the TB+iSB group, timing begins when local anesthesia is started on the MRI lesion side. For the TB+SB group, timing begins when bilateral local anesthesia is started.
• Total Number of Biopsy Cores [During the biopsy procedure]: The total number of biopsy cores, including MRI-targeted and systematic biopsy cores, obtained for each participant will be recorded.
• Number of Pathology Specimen Containers [Periprocedural]: The total number of pathology specimen containers generated from the biopsy procedure will be recorded for each participant.
• Total Pathology-Related Costs [Up to 2 weeks after biopsy]: Total pathology-related costs associated with biopsy specimen handling, processing, histological examination, and pathology reporting will be obtained from the applicable hospital records for each participant.
• Incidence of Biopsy-Related Adverse Events and Complications [From biopsy through 30 days after biopsy; assessed within 30 minutes, at 24 hours, day 7 (±2 days), and day 30 (±7 days)]: The proportion of participants experiencing any biopsy-related adverse event or complication will be assessed. Events include gross hematuria, hematospermia, perineal hematoma, fever or infection, urinary retention, syncope, emergency department visits, unplanned or prolonged hospitalization, serious adverse events, and additional medical interventions required because of a complication.
• Severity of Biopsy-Related Complications by Clavien-Dindo Grade [From biopsy through 30 days after biopsy]: The maximum Clavien-Dindo grade of biopsy-related complications will be recorded for each participant. Grades range from I to V, with higher grades indicating greater severity: Grade I indicates a minor deviation from the expected postoperative course; Grade II requires pharmacological treatment; Grade III requires an intervention; Grade IV indicates a life-threatening complication requiring intensive care; and Grade V indicates death.
• Change From Baseline in International Prostate Symptom Score [Baseline and 7 days after biopsy (±2 days)]: The International Prostate Symptom Score consists of 7 questions assessing lower urinary tract symptoms. The total score ranges from 0 to 35, with higher scores indicating more severe urinary symptoms. Change from baseline will be calculated as the score at 7 days after biopsy minus the baseline score.
• Change From Baseline in IPSS Quality of Life Score [Baseline and 7 days after biopsy (±2 days)]: The quality of life question associated with the International Prostate Symptom Score ranges from 0 to 6, with higher scores indicating greater dissatisfaction with the participant's urinary condition. Change from baseline will be calculated as the score at 7 days after biopsy minus the baseline score.
• Number of Histology Slides [Up to 2 weeks after biopsy]: The total number of histology slides generated for biopsy specimen processing and pathological diagnosis will be recorded for each participant.

Other outcomes

• Real-Time Ultrasound Visibility of MRI-Suspicious Lesions [During MRI/ultrasound cognitive fusion targeted biopsy]: Each MRI-suspicious lesion designated as L1, L2, or L3 will be classified according to whether it can be identified on real-time ultrasound during MRI/ultrasound cognitive fusion targeted biopsy. Categories are visible, not visible, uncertain, and not applicable. The number and proportion of MRI-suspicious lesions in each category will be reported.
• ISUP Grade Group Concordance Between Biopsy and Radical Prostatectomy Pathology [Up to 6 months after biopsy]: Among participants who undergo radical prostatectomy, the relationship between biopsy ISUP Grade Group and radical prostatectomy ISUP Grade Group will be classified into three mutually exclusive categories: concordant, upgraded, or downgraded. Concordant is defined as the same ISUP Grade Group on biopsy and radical prostatectomy pathology; upgraded is defined as a higher ISUP Grade Group on radical prostatectomy pathology than on biopsy pathology; and downgraded is defined as a lower ISUP Grade Group on radical prostatectomy pathology than on biopsy pathology. The number and proportion of participants in each category will be reported.

Sex: Male, ages: 19 Years to any

Inclusion Criteria:

* Male participants older than 18 years.
* Suspected prostate cancer and scheduled to undergo transperineal prostate biopsy.
* Prostate MRI showing a unilateral lesion with a highest Prostate Imaging Reporting and Data System (PI-RADS) score of 4 or 5.
* Serum prostate-specific antigen (PSA) level of 20 ng/mL or lower.
* Able to tolerate and undergo transperineal prostate biopsy.
* Willing to participate in the study and able to provide written informed consent.

Exclusion Criteria:

* Prior prostate biopsy.
* Prior prostate-related treatment or procedure that may affect pathological assessment or interpretation of the biopsy results, including but not limited to androgen deprivation therapy for prostate cancer, radiotherapy, focal therapy, or transurethral prostate surgery.
* Prostate MRI showing a lesion crossing the prostatic midline such that the lesion side cannot be clearly determined, or an independent contralateral lesion with a PI-RADS score of 3 or higher.
* Acute urinary tract infection, severe coagulation disorder, or any other contraindication to transperineal prostate biopsy.
* In the investigator's judgment, inability to understand the study, comply with study procedures, or provide written informed consent.

• Results publication: Cheng Y, Huang H, Wang M, Zhu L, Peng S, Li D, Marra G, Qi R, Ding X, Liu M, Qiu X, Guo H. Magnetic resonance imaging-targeted biopsy with index lesion ipsilateral or bilateral systematic biopsy in prostate cancer: A multicenter, paired, noninferiority, observational trial. Cancer. 2026 Jul 1;132(13):e70493. doi: 10.1002/cncr.70493. PMID 42319125