Prostate cancer is the second most diagnosed malignancy among men worldwide. Despite substantial advances in MRI–guided diagnostic pathways, prostate biopsy with histopathological evaluation remains indispensable for definitive diagnosis. Historically, transrectal biopsy (TRBx) has been the standard approach; however, concerns regarding infectious complications have driven a shift toward transperineal biopsy (TPBx). In 2015, the European Association of Urology (EAU) Urological Infections Guidelines Panel initiated a systematic review and meta-analysis, first published in 2020, and subsequently updated annually. The initial analysis included seven randomised controlled trials (RCTs) involving 1330 patients comparing infectious outcomes between biopsy routes. TPBx was associated with significantly fewer infectious events than TRBx (22/673 vs. 37/657), yielding a risk ratio of 0.55. These findings led to a revision of EAU guidelines, prioritising TPBx as the preferred biopsy approach. This transition coincided with the TREXIT (EXIT from TRansrectal biopsy) initiative, which further accelerated global adoption of TPBx. As TPBx has become more widely implemented, research priorities have expanded beyond infection prevention to include cancer detection rates, cost-effectiveness, and procedure-related morbidity such as urinary retention. Over the past year, five major RCTs (ProBE-PC, PERFECT, PREVENT, TRANSLATE and Tricard et al.) have consistently demonstrated higher post-biopsy infection rates with TRBx, reinforcing the EAU recommendation in favour of TPBx. A recent meta-analysis further supports TPBx as the emerging gold standard. Notably, several recent trials performed TPBx without antibiotic prophylaxis yet reported lower infection rates than TRBx. Only two RCTs have directly evaluated antibiotic prophylaxis in TPBx, both demonstrating exceedingly low infection rates regardless of prophylactic use. A comprehensive meta-analysis incorporating randomised and observational studies similarly found no significant differences in infection-related outcomes, with absolute sepsis rates below 0.2%. In conclusion, TPBx is a demonstrably safe procedure, and current evidence suggests that routine perioperative antibiotic prophylaxis confers minimal additional benefit. Omitting antibiotics represents an important advance in antimicrobial stewardship and may be appropriate for low-risk patients undergoing TPBx.

