PROSTATE CANCER Randomized Controlled Trials to Inform Prostate Biopsy Debate
By: Badar M. Mian, MD, FACS, Albany Medical Center, New York | Posted on: 07 Sep 2023
Transrectal prostate biopsy (TR-Bx), a long-held standard for prostate cancer detection, is among the most common urological procedures worldwide. The procedure has undergone several refinements over the last 3 decades to address 2 major concerns, namely the sampling error that is inherent to the ultrasound-guided systematic (random) biopsy and infectious complications. The integration of prebiopsy multiparametric MRI into the diagnostic pathway and the subsequent MRI-targeted TRBx has significantly reduced the sampling error and improved the detection of clinically significant prostate cancer.1,2
More concerning than the diagnostic yield are the reports demonstrating rising rates of post−TR-Bx infections. As many as 30%-50% of Escherichia coli isolates, the most common organism reported in postbiopsy infections, may be resistant to fluoroquinolones and other commonly used antibiotics.3,4 Consequently, some centers have reported postbiopsy infection rates of >10% while others report a 2-fold to 4-fold increase in infectious complications.5,6
Several strategies have been employed to decrease the risk of infectious complications. The antibiotic-based preventive strategies have included the use of broad-spectrum antibiotics, longer antibiotic course, antibiotics targeted to rectal cultures, and multiagent augmented antibiotic prophylaxis.7-9 The nonantibiotic preventive strategies have focused on antiseptic measures including cleansing the biopsy needle after each sample using formalin or alcohol, and rectal preparation using chlorhexidine, antimicrobial lubricants, or povidone-iodine solution.10 Of the nonantibiotic preventive measures povidone-iodine rectal preparation appears most promising in reducing infectious complications without escalating antibiotic usage.11
Primarily due to the concerns surrounding infectious complications, experts have proposed the utilization of transperineal prostate biopsy (TP-Bx) as the preferred alternative to the TR-Bx procedure.12 Several observational studies have indicated that TP-Bx is associated with a lower risk (∼1%) of postbiopsy infections,13-15 and improved detection of clinically significant prostate cancer. The European Association of Urology guidelines recommend abandoning TR-Bx and switching to TP-Bx.
Despite the promising results from several observational studies favoring TP-Bx, a number of barriers to the adoption of TP-Bx have been identified.16 TP-Bx is associated with increased discomfort (and possible need for sedation), longer procedure time, need for additional durable and disposable instruments, and increased cost. Other than being resource-intensive, TP-Bx is less familiar to the large majority of urologists, necessitating additional training for physicians and clinical staff. Perhaps the most important barrier is the lack of level 1 evidence and conflicting guidelines. The AUA guidelines, in contrast to the European guidelines, have a neutral stance, without favoring one procedure over the other. Emerging reports from observational studies have demonstrated infectious complication rates to be somewhat similar between the TR-Bx and TP-Bx approaches.17,18 With an estimated 2 million prostate biopsy procedures performed annually in North America and Europe, a major shift in clinical practice, such as abandoning a procedure, must be guided by strong comparative effectiveness studies. To date, there is a distinct lack of randomized clinical trials (RCTs) directly comparing the complications and efficacy of TR-Bx and TP-Bx procedures.
Until recently, RCTs comparing the 2 biopsy procedures were deemed unnecessary. Fortunately, a number of investigators and funding agencies have recognized this gap in scientific evidence. At present, several large RCTs have been initiated that are well powered and specifically designed to compare the infectious complications and/or diagnostic efficacy of the 2 biopsy procedures. A few of the selected RCTs are listed in the Table. With the recognition of the lower quality of existing evidence in the European guidelines, and the stated desire to incorporate future RCT data in the American guidelines, the need for strong evidence has taken its rightful place in the prostate biopsy debate.
Table. Selected Randomized Controlled Trials Comparing Transrectal and Transperineal Prostate Biopsy Procedures
|NCT No.||Study title||Start datea||Enrollment||Hypothesis||Study population||Participants (N)||Primary outcome||Secondary outcomesb||Sponsor|
|NCT04081636||Prostate Biopsy Efficacy and Complications (ProBE-PC study)||9/2/2019||Completed||TP-Bx is superior to TR-Bx in reducing infectious complications||All men undergoing prostate biopsy (biopsy-naïve and previous negative)||774||Rate of infectious complications||Clinically significant prostate cancer detection rate; hemorrhagic complications; tolerability, pain scores; patient-reported urinary and sexual function; cost-effectiveness||Albany Medical Center|
|NCT04843566||Evaluation of Transperineal Biopsy Under Local Anesthesia||3/22/2021||Recruiting||MRI-targeted TP-Bx compared to MRI-targeted TR-Bx has a much lower risk of infection||Biopsy-naïve men||400||Change in infection-related adverse events||Pain and discomfort; detection of clinically significant prostate cancer||Weill Medical College of Cornell University|
|NCT04815876||Transperineal vs Transrectal MRI-targeted Prostate Biopsy||6/24/2021||Recruiting||MRI-targeted TP-Bx compared to MRI-targeted TR-Bx has a much lower risk of infection||Men on active surveillance; men with prior negative biopsy||1,302||Change in infection-related adverse events||Pain and discomfort; detection of clinically significant prostate cancer||Weill Medical College of Cornell University|
|NCT05179694||Transrectal Biopsy vs Local Anesthetic Transperineal Biopsy in Evaluation (TRANSLATE) of Men With Potential Clinically Significant Prostate Cancer||12/3/2021||Recruiting||Superior detection rate of clinically significant prostate cancer with TP-Bx||Biopsy-naïve men||1,042||Detection of clinically significant prostate cancer||Infectious complications; health-related quality of life; tolerability and pain; patient-reported complication; cost-effectiveness||University of Oxford|
|NCT05069584||Transperineal Fusion Biopsy Versus Transrectal (PERFECT trial)||1/17/2022||Completed||Targeted TP-Bx is noninferior to targeted TR-Bx diagnostic efficiency||Biopsy-naïve men, with PI-RADS 4-5 lesion on MRI||270||Detection of clinically significant prostate cancer||None listed||GCS Ramsay Santé Pour l’Enseignement et la Recherche|
|Abbreviations: MRI, magnetic resonance imaging; PI-RADS, Prostate Imaging Reporting & Data System; TP-Bx, transperineal biopsy; TR-Bx, transrectal biopsy.
Data were obtained from www.clinicaltrials.gov on July 1, 2023.
aStart dates are listed in chronological order.
bClinically significant prostate cancer is defined as Gleason score ≥7 or grade group ≥2.
- Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378(19):1767-1777.
- Moldovan PC, Van Den Broeck T, Sylvester R, et al. What is the negative predictive value of multiparametric magnetic resonance imaging in excluding prostate cancer at biopsy? A systematic review and meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel. Eur Urol. 2017;72(2):250-266.
- Redgrave LS, Sutton SB, Webber MA, Piddock LJ. Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol. 2014;22(8):438-445.
- Chung HS, Hwang EC, Yu HS, et al. Prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy: a prospective multicenter study. Int J Urol. 2018;25(3):278-283.
- Roberts MJ, Bennett HY, Harris PN, et al. Prostate biopsy-related infection: a systematic review of risk factors, prevention strategies, and management approaches. Urology. 2017;104:11-21.
- Skouteris VM, Crawford ED, Mouraviev V, et al. Transrectal ultrasound-guided versus transperineal mapping prostate biopsy: complication comparison. Rev Urol. 2018;20(1):19-25.
- Liss MA, Kim W, Moskowitz D, Szabo RJ. Comparative effectiveness of targeted vs empirical antibiotic prophylaxis to prevent sepsis from transrectal prostate biopsy: a retrospective analysis. J Urol. 2015;194(2):397-402.
- Jiang P, Liss MA, Szabo RJ. Targeted antimicrobial prophylaxis does not always prevent sepsis after transrectal prostate biopsy. J Urol. 2018;200(2):361-368.
- Hadjipavlou M, Eragat M, Kenny C, et al. Effect of augmented antimicrobial prophylaxis and rectal swab culture-guided targeted prophylaxis on the risk of sepsis following transrectal prostate biopsy. Eur Urol Focus. 2020;6(1):95-101.
- Pilatz A, Veeratterapillay R, Köves B, et al. Update on strategies to reduce infectious complications after prostate biopsy. Eur Urol Focus. 2019;5(1):20-28.
- 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.
- 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.
- Xiang J, Yan H, Li J, Wang X, Chen H, Zheng X. Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis. World J Surg Oncol. 2019;17(1):31.
- Loy LM, Lim GH, Leow JJ, Lee CH, Tan TW, Tan CH. A systematic review and meta-analysis of magnetic resonance imaging and ultrasound guided fusion biopsy of prostate for cancer detection—comparing transrectal with transperineal approaches. Urol Oncol. 2020;38(8):650-660.
- Tu X, Liu Z, Chang T, et al. Transperineal magnetic resonance imaging-targeted biopsy may perform better than transrectal route in the detection of clinically significant prostate cancer: systematic review and meta-analysis. Clin Genitourin Cancer. 2019;17(5):e860-e870.
- Mian BM, Kaufman RP Jr, Fisher HAG. Rationale and protocol for randomized study of transrectal and transperineal prostate biopsy efficacy and complications (ProBE-PC study). Prostate Cancer Prostatic Dis. 2021;24(3):688-696.
- Young R, Norris B, Reeves F, Peters JS. A retrospective comparison of transrectal and transperineal prostate biopsies: experience of a single surgeon. J Endourol. 2019;33(6):498-502.
- Lopez JF, Campbell A, Omer A, et al. Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis. BJU Int. 2021;128(3):311-318.