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 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.
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