Background Transperineal prostate biopsy (TP-Bx) is increasingly favored over the transrectal approach due to its lower rate of infectious complications. Emerging evidence suggests that TP-Bx can often be safely performed without antibiotic prophylaxis in low-risk patients. However, there is no international consensus on the clinical risk factors that justify prophylactic antibiotic use, leading to wide practice variability and concerns regarding antimicrobial stewardship.

Objective This Delphi consensus study aims to identify and define procedural, patient-related, and microbiological risk factors that warrant antibiotic prophylaxis in TP-Bx and to establish evidence-informed best practice recommendations.

Methods A modified three-round Delphi process will be conducted in accordance with ACCORD and CREDES guidelines. A diverse panel of 50–60 international experts in urology, infectious diseases, microbiology, and antimicrobial stewardship will anonymously evaluate predefined and newly suggested risk factors using a 6-point Likert scale. Consensus will be defined as ≥70% of participants rating an item as highly important (score 5–6) and <15% rating it as unimportant (score 1–2). Items failing to reach consensus in Rounds 1 and 2 will be re-evaluated in subsequent rounds.

Outcomes The primary outcome will be a consensus-based list of risk factors justifying antibiotic prophylaxis in TP-Bx. Secondary outcomes include recommendations for diagnostic testing, prophylactic regimens, and thresholds for initiating routine prophylaxis based on institutional infection rates.

Dissemination Findings will be submitted for publication in peer-reviewed journals to support global efforts in harmonizing practice and promoting responsible antibiotic use in prostate cancer diagnostics.

The authors have declared no competing interest.

The study is not funded but the platform for the Delphi Consensus (Within3) will be provided via an unrestricted grant by Advanz Pharma.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors