Choosing the path: insights into transperineal vs. transrectal prostate biopsy

Prostate biopsy is the gold standard for confirming the histologic diagnosis of prostate cancer. This procedure is incredibly common with approximately one million prostate biopsies performed annually in the Medicare population alone (1). The number of biopsies performed per annum is only expected to increase as the United States population aged 65 years and older continues to grow and life expectancy across the population becomes greater. Furthermore, the increased adoption of active surveillance for low-risk prostate cancer necessitates repeat or serial prostate biopsies in the follow-up algorithm (2). As a result, providing the safest and most efficacious procedure for patients is paramount.

With regards to complications, most noninfectious etiologies, such as hematuria, hematochezia, urinary retention, hematospermia, can be managed conservatively (2). However, sepsis is a rare but life-threatening complication that poses major concern for providers due to its associated morbidity and health care costs. Infectious complications after prostate biopsy are reported to occur between 2–5% of cases, with the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial citing a rate of 7.8 infectious complications per 1,000 biopsies, but without any additional deaths (3). The introduction of fecal flora into the highly vascular prostate through a transrectal (TR) approach is believed to increase a patient’s risk of infection despite appropriate antibiotic prophylaxis. This may be both due to and contribute to rising antimicrobial resistance, putting future patients receiving primary or even subsequent biopsies at an incrementally greater risk for complications (1).

Due to these concerns, transperineal (TP) prostate biopsy has been considered as an alternative to the standard TR approach. In 2003, Emiliozzi et al. conducted a prospective study of patients that received both TP and TR biopsies and found that cancer detection was higher with the TP approach, with TP cancer detection at 38% vs. 32% in TR (4). Another study of complications following TP biopsy in 8,500 men reported that only about 1.5% of patients had a post-operative hospitalization. Urinary tract infection (UTI) with fever was the reason for a third of these hospitalizations, but none of these patients developed sepsis (5). Other studies have much demonstrated a greater degree of equipoise between the modalities. Specifically, Hu et al.’s recent multicenter randomized trial provided evidence in favor of comparability in infectious outcomes. In this study, 658 biopsy-naive participants received either TP biopsy without antibiotic prophylaxis or TR biopsy with targeted prophylaxis after rectal culture screening. The study results demonstrated no statistically significant difference in post-biopsy infections, similar detection of clinically significant prostate cancer, and only minor worsened periprocedural pain that resolved by 7 days in the TP arm. Notably, there were no infections observed in the TP arm. As a result, the authors concluded that office-based TP biopsy would be a tolerable and effective alternative to the traditional TR biopsy for detection and surveillance of prostate cancer (6). In a follow-up research letter, Hu et al. reported that under intent-to-treat analysis, there was a statistically significant difference in post-operative infections between the TR and TP groups (P=0.02). The TP arm still reported no infections, while the TR group had six grade 2 infections (7).

Additional studies have suggested similar type observations. Guo et al. investigated ultrasound guided TP and TR biopsy approaches, finding no difference in cancer detection rates or complications rates, including both non-infectious and infectious alike (8). In the Prostate Biopsy Efficacy and Complications (ProBE-PC) trial, Mian et al. reported insignificant differences between the two modalities with regards to both infectious and noninfectious complications (9). Detection of clinically significant prostate cancer in both arms were also similar between TP and TR modalities, at 43.2% and 47.1%, respectively with odds ratio 1.17, 95% confidence interval from 0.88–1.55 (10). These studies all compared TP biopsy to TR biopsy with augmented prophylaxis, which, though not generally recommended by guidelines, is the most commonly used approach in the US (6). Hu et al.’s findings demonstrated a statistically significant decrease in infectious outcomes in TP compared to TR biopsy with targeted prophylaxis (7). While promising, this benefit may not currently be as generalizable due to the widespread application of augmented prophylaxis regimens.

Regardless, it is unsurprising that there has been an increase in the uptake of TP prostate biopsies. In a 2018 retrospective analysis of the National Prostate Cancer Audit by Skouteris and colleagues, 18% of the 73,630 included participants had received a TP biopsy (11). Thereafter, the European Association of Urology 2021 guidelines began recommending TP approaches for prostate biopsy due to the lower risk of infectious complications (12). Recently, the Pennsylvania Urologic Regional Collaborative (PURC) reported that that TP biopsies rose from only 0.4% of prostate biopsies to 2.9% between 2015 and 2019 within the collective (13). Worldwide, studies continue to suggest similar if not better cancer detection rates by TP approaches (14), especially when diagnosing anterior gland prostate cancer (15). Collectively, these experiences suggest that the use of TP prostate biopsies will only continue to rise, as studies such as Hu et al. continue to validate the comparative effectiveness of the TP (compared to TR) approach. Admittedly, the actuarial rates of adoption remains to be seen.

It is important to consider that although the TP biopsy approach is gaining increasing traction, there are still numerous challenges with the uptake of this modality. The procedure itself requires more time to perform than a TR prostate biopsy, and at this moment, is still more expensive and complex to execute (16). Additionally, reimbursement from payors for prostate biopsy is the same irrespective of approach, thereby creating a financial disincentive for urologists to embrace this technique. Its use in the office setting is fairly new, and the integration of adjunct technologies, such as magnetic resonance imaging (MRI), may require offices to invest in more expensive equipment that may be less accessible for patients or providers, especially in lower income or resource poor regions. These instruments may include (but are not limited to) different probes, higher levels of anesthesia, disposable grids, and other supplies that are not necessary when conducting a standard TR biopsy. TP biopsy has been found to be more painful and embarrassing than TR biopsy, and educational techniques to ameliorate pain management and improve patient experience are still needed (17). Additionally, there may also be a learning curve associated with the uptake of TP biopsy approaches because of current urologists’ familiarity with the TR approach (18). As a result, most urologists still practice TR biopsy approaches and have not completely abandoned the approach (14). When considering all these other difficulties that come with performing a TP biopsy, it seems that uptake will still be a challenge for the near future.

Understanding that TR biopsy is still the most commonly used modality for prostate biopsy, we would be remiss to not mention some key factors that can inherently reduce infectious risk associated with this procedure. The 2017 White Paper from the American Urological Association (AUA) highlights several strategies which can easily be implemented into clinical practice (19). Given the increasing prevalence of quinolone resistant flora colonizing the rectal vault, rectal swab cultures can be used to tailor targeted antibiotic regimens. This prevents practitioners from prescribing an antibiotic regimen that may not prove as effective (19). Singh et al. found in their 2017 study that 41.7% of patients undergoing TR prostate biopsy had fluoroquinolone-resistant E. coli upon examination of pre-procedural rectal swab culture (20), suggesting that use of rectal swab culture and targeted prophylaxis would allow for proper risk reduction of infection in over a third of patients receiving prostate biopsy.

Secondly, another way to reduce the risk of TR biopsy infection is by providing augmented antibiotic regimens for patients with certain risk factors. Such considerations would include, but not be limited to: a medical history of diabetes, UTIs, prostatitis, comorbidities with a Charlson score greater than 1, immunosuppression, as well as recent exposure to antibiotics or international travel (19). This augmented regimen would consist of a fluoroquinolone and an additional antibiotic, such as a 1^st, 2^nd, or 3^rd generation cephalosporin or aminoglycosides (19). In a 2020 meta-review, augmented regimens were found to be superior to standard single agent prophylaxis at reducing infectious complications, though the authors noted that augmented regimens can sometimes contradict proper antibiotic stewardship (21). The primary concern regarding ubiquitous used of augmented regimens is the contribution to future antibiotic resistance. Therefore, consideration of risk factors for infection is critical before utilizing this approach.

Thirdly, during TR biopsies, topical rectal antiseptics can be used as a low-cost, simple way to protect against infection. The use of rectal povidone-iodine preparations (PIRPs) along with standard oral antibiotic prophylaxis have been found to significantly reduce post-biopsy infections (22), while data on chlorhexidine preparations indicated that use correlated with reduced need for perioperative intravenous antibiotics (23). Local antiseptic strategies reduce the micro-organism colony counts in the rectal vault and in turn the potential for translocation of bacteria into the highly vascular prostate. Additionally, dipping biopsy needles in formalin prior to use and repeating this before each core is taken can help with infection prevention. A recent prospective study found that needles disinfected with formalin had significantly less bacterial growth compared to needles that were not disinfected with formalin. This, in turn, translated to a lower infection rate (0% formalin vs. 7.5% control) for treated patients (24). Notably, these different strategies are not mutually exclusive and can be used in conjunction during procedures to minimize infectious risk.

Finally, if conducting a transrectal ultrasound (TURS) guided biopsy, single use ultrasound gel should be employed to reduce risk of infection. In 2017, the European Society of Radiology Working Group recommended that all major and minor ultrasound guided interventional procedures, such as TR biopsies, use sterile gel. This is because compared to single use gel, multiple use gel has various pathways for pathogen proliferation, including incubation in warm temperatures, contamination of the gel dispensing tip, and contamination during refills (25). Engaging in such preventative practices when conducting TR biopsies can help reduce the risk of infection with this procedure in the meantime while the urologic landscape continues adopting the TP approach.

The current evidence provides strong recommendation for TP biopsy implementation. Hu et al.’s randomized trial demonstrates that a TP prostate biopsy without antibiotics is equivalent to a TR biopsy with targeted antibiotic prophylaxis when it comes to infectious outcomes adds to this viewpoint. Their conclusions align with proper antibiotic stewardship and may aid in efforts to reduce antimicrobial resistance and post-procedure infections. These findings also add to the growing literature highlighting that the TP modality is just as effective at detecting clinically significant prostate cancer as the TR approach. At this point, future efforts should be aimed towards facilitating adoption of this approach, as there are still numerous implementational barriers to increasing the use of the TP modality. Additionally, the continuous use of TR biopsy is expected. Incorporation of well vetted protocols to minimize infection with TR approaches should be part of the standard in most practices. The procedure’s efficacy has long been proven, however, as more urologists are trained in a TP approach, it is likely the number of TR biopsies performed annually will decline.

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-2024-754/prf

Funding: The Ken and Bonnie Shockey Fund for Urologic Oncology Research at Penn State Health.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2024-754/coif). The authors have no 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.

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