A Multicenter, Randomized Controlled Superiority Trial Comparing Robotic-Assisted Versus Expert Cognitive Fusion Prostate Biopsy in Obese Men

A Multicenter, Randomized Controlled Superiority Trial Comparing Robotic-Assisted Versus Expert Cognitive Fusion Prostate Biopsy in Obese Men

The trial aims to find out if using a robotic system to help perform prostate biopsies is better than having a highly experienced doctor perform the biopsy by hand in men with a high Body Mass Index (BMI).

While MRI-guided prostate biopsies are highly effective, carrying them out in men with obesity can be physically challenging for doctors. Extra pelvic tissue increases the depth the biopsy needle must travel and makes it difficult to manually hold the ultrasound probe perfectly steady. This physical difficulty might cause doctors to miss some aggressive prostate cancers.

This study tests whether a robotic arm-which completely locks the biopsy needle on target and eliminates human hand tremors-can improve cancer detection. The study will enroll up to 570 men with high BMI who have suspicious areas on their prostate MRI. Participants will be randomly assigned to receive either a robotic-assisted biopsy or a standard manual biopsy performed by an expert urologist.

To ensure the results are completely unbiased, participants will not know which method is being used on them. They will be placed behind a surgical drape and wear noise-canceling headphones playing music during the procedure to block out the sounds of the robotic motors. The main goal is to see if the robotic method safely and significantly increases the detection rate of clinically significant prostate cancer in this specific group of patients.

The integration of multiparametric magnetic resonance imaging (mpMRI) with transperineal targeted biopsy has established a new standard for prostate cancer diagnosis. However, clinical evidence, including findings from the previous IMAGINATION trial, suggests that the diagnostic accuracy of manual targeted biopsy techniques degrades significantly in patients with high Body Mass Index (BMI).

Deep perineal adiposity creates a "hostile anatomical environment." It increases the skin-to-apex distance and introduces a "fulcrum effect," where the extensive soft tissue acts as a pivot point that amplifies manual tremors and restricts the operator's physical ability to steer the transperineal probe accurately. This mechanical barrier contributes to the "Obesity Paradox," wherein men with obesity face a higher risk of harboring undiagnosed, advanced high-grade prostate cancer.

The ROBUST (Robotic Optimization for Biopsy Under Substantial Tissue) trial is an investigator-initiated, international, multicenter, randomized controlled trial designed to determine if robotic stabilization can serve as a "technical equalizer" for this specific anatomical challenge.

Unlike conventional device trials, ROBUST utilizes a Bayesian adaptive hierarchical non-inferiority to superiority design. It aims to test whether robotic-assisted fusion biopsy is strictly non-inferior (with a -5% margin), and subsequently superior, to expert cognitive fusion biopsy. To rigorously isolate the impact of mechanical stabilization from operator inexperience, the control arm explicitly represents "peak human performance," mandating that human operators be credentialed experts with a documented history of >500 total prostate biopsies and >200 cognitive fusion targeted cases.

To eliminate performance bias and placebo effects on patient-reported outcomes (such as procedural anxiety and pain), the trial implements a strict single-blind (patient-blinded) protocol. A high surgical drape and noise-canceling headphones are utilized to completely mask the distinct motor operations of the robotic platform from the participant.

Furthermore, to mitigate the inherent recruitment fatigue associated with this highly specific demographic, the study incorporates a Bayesian sequential monitoring framework. An independent Data Safety Monitoring Board (DSMB) will evaluate Posterior Probability and Predictive Probability of Success (PPOS) at predefined interim looks (N=200, 300, and 400). This allows the trial to be halted early for either overwhelming efficacy or objective futility. By strictly targeting the "stress test" population, ROBUST seeks to provide Level 1 evidence for a risk-stratified precision diagnostic pathway, evaluating whether high-cost robotic technology is an absolute clinical necessity for men with obesity.

Inclusion Criteria:

• Age ≥ 40 years.
• Serum PSA levels between 4 and 20 ng/ml and/or abnormal digital rectal examination (DRE).
• High Body Mass Index (BMI): defined as ≥ 28 kg/m ² for Asian cohorts and ≥ 30 kg/m ² for Non-Asian cohorts.
• MRI-Positive: Presence of at least one suspicious lesion (PI-RADS score ≥ 3) on mpMRI.
• Fitness for transperineal biopsy under local anaesthesia or conscious sedation.

Exclusion Criteria:

• Prior treatment for prostate cancer.
• History of major anorectal surgery preventing safe transperineal probe insertion.
• Contraindications to MRI.
• Negative screening MRI (PI-RADS 1-2).