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Protocol of a Multicentre Randomised Controlled Trial Assessing Transperineal Prostate Biopsy to Reduce Infectious Complications - Beyond the Abstract

We describe the rationale and protocol for a multicenter, prospective randomized controlled trial (RCT) comparing outcomes of transperineal vs. transrectal approaches for prostate biopsy.1 Currently, there is controversy with regards to the best approach to prostate biopsy. Approximately one million prostate biopsies are performed annually in the United States, and most are performed using the transrectal approach.2 However, the risk of post-biopsy infections is increasing due to greater antibiotic resistance of rectal flora.3 Studies demonstrate that the percutaneous transperineal approach to prostate biopsy may have fewer infections4 as well as better detection of clinically significant (Grade Group ≥2) prostate cancer.5 Review of contemporary outcomes led European Association of Urology (EAU) guidelines to strongly recommend the transperineal approach.6

Despite the increasing allure for the transperineal approach to prostate biopsy,7 several challenges limit its greater adoption in the United States. First, the transperineal technique is relatively novel gaining popularity in the past 5 to 6 years, and therefore, most urologists have not received formal training in this approach. Moreover, most younger urologists have no exposure to the transperineal technique during training: our recent international survey demonstrated that less than half of urology trainees reported exposure to transperineal biopsy.8

Secondly, transperineal and transrectal biopsy share the same administrative code and therefore are reimbursed the same amount. Most urologists use the PrecisionPoint® device to perform transperineal biopsies,9 which costs at least $200 per case. Currently, insurance companies do not compensate for the greater cost and time needed to perform a transperineal biopsy. Given the prostate biopsy procedure is one of the most commonly performed urologic procedures,10 the added costs present a significant economic burden on practicing urologists.

Third, and most importantly, there is a lack of high-quality evidence demonstrating significant benefit of the transperineal biopsy with regards to reducing infectious complications as well as improving cancer detection. The EAU recommendation for transperineal biopsy were driven by meta-analyses and retrospective studies of single-center data. Importantly, these studies were not designed and powered to evaluate infectious complications as the primary outcome. In contrast, the recent American Urological Association (AUA) guidelines for the early detection of prostate cancer advocate for either a transrectal or transperineal biopsy approach, given absence of high-quality data confirming the benefit of the transperineal approach.11 Furthermore, new evidence from Mian et al demonstrated no difference in infectious complications for 351 transperineal vs. 367 transrectal biopsy (2.7% vs. 2.6%, p= ).

Our trial bridges critical knowledge gaps in this controversy over the utilization of the transperineal versus transrectal prostate biopsy techniques. We aim to recruit approximately 1,700 men for the first-time biopsy, prior negative biopsy, and active surveillance indications across 10 sites. This is noteworthy given that quinolone resistance varies from 11% to 56% across states.12 Prostate magnetic resonance imaging (MRI) will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to a systematic biopsy (12 cores). Men randomized to the transperineal biopsy arm will not receive antibiotic prophylaxis while men randomized to the transrectal biopsy arm will under a targeted prophylaxis regimen guided by rectal swab. Our primary outcome will be infectious complications, and secondary outcomes include non-infectious adverse events (bleeding, urinary retention), pain/discomfort/anxiety, and detection of clinically significant prostate cancer.

Historically, RCTs of surgical techniques are difficult to execute due to lack of equipoise and investigator time and effort to enroll patients. Furthermore, psychological barriers exist that impede patient recruitment and randomization. In order to improve the conduct of surgical trials, our study will utilize innovative recruitment techniques, such as the two-stage consent,13,14 which minimizes patient burden in order to overcome some of the challenges of performing surgical RCTs. Other aspects of our trial that may overcome traditional barriers to surgical RCTs include a relatively short and straight-forward procedure, which minimizes surgeon variation, as well as an outcome (infectious complications) that is infrequent and presents within 2-3 days after the procedure.

In summary, high-level, prospective evidence demonstrating the best risk-to-benefit ratio for men undergoing different prostate biopsy techniques is lacking. We aim to compare the safety, tolerability, and cancer detection rates of transperineal prostate biopsy versus transrectal prostate biopsy in a multicenter RCT.

Written by: Alec Zhu, MD, & Jim C. Hu, MD, MPH

Department of Urology, NewYork-Presbyterian Weill Cornell Medical Center, New York, New York, USA.

References:

  1. Hu J, Zhu A, Vickers A, et al. Protocol of a multicentre randomised controlled trial assessing transperineal prostate biopsy to reduce infectiouscomplications. BMJ Open. 2023;13(5):e071191. doi:10.1136/bmjopen-2022-071191
  2. Loeb S, Carter HB, Berndt SI, Ricker W, Schaeffer EM. Complications after prostate biopsy: data from SEER-Medicare. J Urol. 2011;186(5):1830-1834. doi:10.1016/j.juro.2011.06.057
  3. Mosharafa AA, Torky MH, El Said WM, Meshref A. Rising incidence of acute prostatitis following prostate biopsy: fluoroquinolone resistance and exposure is a significant risk factor. Urology. 2011;78(3):511-514. doi:10.1016/j.urology.2011.04.064
  4. Pradere B, Veeratterapillay R, Dimitropoulos K, et al. Nonantibiotic Strategies for the Prevention of Infectious Complications following Prostate Biopsy: A Systematic Review and Meta-Analysis. J Urol. 2021;205(3):653-663. doi:10.1097/JU.0000000000001399
  5. Meyer AR, Mamawala M, Winoker JS, et al. Transperineal Prostate Biopsy Improves the Detection of Clinically Significant Prostate Cancer among Men on Active Surveillance. J Urol. 2021;205(4):1069-1074. doi:10.1097/JU.0000000000001523
  6. Pilatz A, Veeratterapillay R, Dimitropoulos K, et al. European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy. Eur Urol. 2021;79(1):11-15. doi:10.1016/j.eururo.2020.10.019
  7. Grummet J, Gorin MA, Popert R, et al. “TREXIT 2020”: why the time to abandon transrectal prostate biopsy starts now. Prostate Cancer Prostatic Dis. 2020;23(1):62-65. doi:10.1038/s41391-020-0204-8
  8. Brant A, Campi R, Carrion DM, et al. Findings from an international survey of urology trainee experience with prostate biopsy. BJU Int. Published online November 24, 2022. doi:10.1111/bju.15935
  9. Urkmez A, Demirel C, Altok M, Bathala TK, Shapiro DD, Davis JW. Freehand versus Grid-Based Transperineal Prostate Biopsy: A Comparison of Anatomical Region Yield and Complications. J Urol. 2021;206(4):894-902. doi:10.1097/JU.0000000000001902
  10. Cruz AP, Skolarus TA, Ambani SN, Hafez K, Kraft KH. Aligning Urology Residency Training With Real-World Workforce Needs. Journal of Surgical Education. 2021;78(3):820-827. doi:10.1016/j.jsurg.2020.09.018
  11. Wei JT, Barocas D, Carlsson S, et al. Early Detection of Prostate Cancer: AUA/SUO Guideline Part II: Considerations for a Prostate Biopsy. J Urol. Published online April 25, 2023:101097JU0000000000003492. doi:10.1097/JU.0000000000003492
  12. Concepcion RS, Schaeffer EM, Shore ND, Kapoor DA, Scott JA, Kirsh GM. The Effect of Local Antibiogram-based Augmented Antibiotic Prophylaxis on Infection-related Complications Following Prostate Biopsy. Rev Urol. 2019;21(2-3):93-101.
  13. Vickers AJ, Vertosick EA, Carlsson SV, Ehdaie B, Kim SYH. Patient accrual and understanding of informed consent in a two-stage consent design. Clin Trials. 2021;18(3):377-382. doi:10.1177/1740774520988500
  14. Vickers AJ, Young-Afat DA, Ehdaie B, Kim SY. Just-in-time consent: The ethical case for an alternative to traditional informed consent in randomized trials comparing an experimental intervention with usual care. Clin Trials. 2018;15(1):3-8. doi:10.1177/1740774517746610

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