Changes in the prostate biopsy landscape—how can we improve quality?

Approximately one million prostate biopsies are performed annually in the United States (1). As recently as 2015, 99% of prostate biopsies were performed via transrectal approach (2). However, the increasing rates of biopsy-associated infections have motivated the development and evaluation of transperineal approaches, in which the biopsy needle avoids the rectal flora (3). In 2024, two large North American trials, ProBE-PC and PREVENT, published their final results, comparing the two biopsy approaches (4,5). These trials, along with other evidence, have started to define a multidimensional measure of prostate biopsy quality, which encompasses cancer detection, infectious complications, and tolerability (i.e., patient-reported pain). Given that the broader implementation of a particular prostate biopsy approach may hinge on this multidimensional measure, we examine this newly defined landscape of prostate biopsy quality.

Clinically significant cancer detection

The detection of clinically significant prostate cancer (i.e., grade group ≥2) remains the overarching goal of a prostate biopsy, regardless of approach. Some retrospective studies suggest differences in detection rates, slightly favoring transperineal biopsy, particularly for anteriorly located tumors. However, these findings likely reflect substantial heterogeneity in procedural technique (e.g., number of cores sampled) (6). Notably, the ProBE-PC and PREVENT trials, point to similar detection rates of clinically significant disease between the two biopsy approaches. Both trials utilized similar underlying biopsy protocols. They required that urologists perform both a targeted fusion biopsy (with three cores per lesion) and a twelve-core systematic biopsy, for both transrectal and transperineal techniques. Almost all patients in both trials (i.e., >95%) underwent pre-biopsy magnetic resonance imaging, reflecting modern practice. In the ProBE-PC trial, clinically significant disease was similarly detected in patients undergoing transrectal (47%) and transperineal biopsy (43%) (4). Similarly, the PREVENT trial—which included only biopsy naïve men—also demonstrated similar rates for transrectal (52%) and transperineal biopsy approaches (55%) (5).

Infectious complications

While the ProBE-PC and PREVENT trials largely aligned regarding the detection of clinically significant disease, they reported different incidence of biopsy-associated infections. The ProBE-PC trial did not demonstrate differences in infection rate between transrectal biopsy with single day antibiotic prophylaxis (2.6%) and transperineal biopsy without antibiotics (2.7%) (7). However, the trial defined a wide range of infection-related outcomes, including undocumented fever and antibiotic prescription for presumed infection, which likely lowered the specificity in identifying true biopsy-associated infections. Conversely, the PREVENT trial included a seven-day survey and medical record review to capture complications and noted a small, but statistically significant higher rate of infections in patients undergoing transrectal biopsy with targeted prophylaxis compared to transperineal approach (1.6% vs. 0%, P=0.02) (5). Importantly, neither trial captured a single sepsis event after prostate biopsy, perhaps its most feared complication. Additionally, a meta-analysis of the ProBE-PC, PREVENT, and PERFECT (based in France) trials was unable to note a statistically robust difference in infections or sepsis (8). Despite these modest effects, proponents of transperineal biopsy note the favorable point estimates of these analyses and that patients might avoid antibiotics. This may allow for a completely antibiotic-free pathway to prostate biopsies in the future. However, concepts regarding the side effects of antibiotics and antibiotic stewardship may be diminished in this setting, where most patients undergoing transrectal biopsy only receive single-dose prophylaxis.

Tolerability and procedure logistics

The last dimension of prostate biopsy quality addresses the tolerability of the procedure. By design, instead of the needle traversing the rectal mucosa, as in transrectal biopsy, transperineal biopsies require that the needle passes through the perineal skin, pelvic floor and bulbocavernosus muscles. This typically makes it it more painful than transrectal biopsy and historically required transperineal biopsy to be performed under general anesthesia (3). Notably, use of general anesthesia, is associated with higher risk of acute urinary retention and long procedural time (9). However, refinement of local anesthesia techniques (i.e., lidocaine administration into the pelvic floor muscles and neurovascular bundles) appears to have narrowed this gap (10). In the PREVENT study, pain score differences between transrectal biopsy (3.0/10) and transperineal biopsy (3.6/10) were small, but statistically significant (adjusted difference =0.6; 95% confidence interval: 0.2, 0.9) (11). Even as these differences are mitigated, the greater pain patients experience with transperineal biopsy may also increase logistical complexity. In a qualitative study of the Michigan Urological Surgery Improvement Collaborative, these concerns regarding patient experience as well as those regarding procedure length and equipment costs, remain barriers to the adoption of transperineal biopsy at the physician-level (12). These challenges may not only steepen the learning curve for urologists transitioning to transperineal biopsy, but they may disincentivize its adoption (7).

Several recent high-quality studies, such as the referenced ProBE-PC trial, have identified the key quality measures when comparing transrectal and transperineal prostate biopsy. These measures include detection of clinically significant prostate cancer, infectious complications, and tolerability. These studies have generated enthusiasm around transperineal biopsy, even leading to its recommendation by European clinical guidelines (13). In a more granular analysis, however, the absolute differences between these two approaches appears small. Additionally, logistical concerns associated with transperineal biopsy may limit it its broader adoption. Going forward, the creation of risk adapted approaches that can more accurately determine which approach should be applied to a particular patient may prove more impactful. While these differences may be small on a patient-level, given the sheer volume of biopsies performed, advances in biopsy quality can improve urologic care quality broadly.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Andrology and Urology. The article has undergone external peer review.

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-34/prf

Funding: A.S. is supported by a training grant from the National Cancer Institute (No. T32 CA180984). T.B. is supported by the Agency for Healthcare Research and quality (No. K08HS028474). S.S.S. is supported by the National Institutes of Health (R37CA283857 and Cancer Center Core grant No. P30CA046592).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-34/coif). A.S. is supported by a training grant from the National Cancer Institute (No. T32 CA180984). He recently received a travel grant from the American Urological Association, not related to this current work. T.B. is supported by the Agency for Healthcare Research and Quality (No. K08HS028474). S.S.S. is supported by the National Institutes of Health (No. R37CA283857 and Cancer Center Core grant No. P30CA046592). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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