Transperineal vs Transrectal Prostate Biopsy—The PREVENT Randomized Clinical Trial

Abstract

This randomized clinical trial compares the effect of transperineal vs transrectal prostate biopsy on infection rates after biopsy.

Prostate biopsy is a common and invasive diagnostic procedure. First-time biopsy detects prostate cancer in more than half of patients,¹ and many with a benign initial biopsy or those receiving active surveillance undergo repeated biopsies. With the international incidence at 1.4 million prostate cancer cases,² more than 3 million prostate biopsies are performed annually. Transrectal prostate biopsy is the predominant approach used and antibiotics are given routinely to prevent infection, which increases societal antimicrobial resistance.

Recently, an alternative transperineal biopsy approach under local anesthesia has increased in use. During this biopsy approach, the needle traverses the cleaned skin of the perineum. Although there are potential advantages to transperineal biopsy, high-level evidence is limited. We reported a funder-mandated interim analysis,¹ and now present the final results after meeting the sample size requirement (369 participants per group).

Methods

In this 10-center clinical trial, patients with suspicion for prostate cancer were randomized to clinic-based transperineal biopsy (without antibiotic prophylaxis) or transrectal biopsy (with targeted prophylaxis, rectal culture screening for fluoroquinolone-resistant bacteria, and antibiotic targeting). The trial protocol appears in Supplement 1. An institutional review board at each site and the Biomedical Research Alliance of New York (18-02-365) provided approval; all participants provided written, informed consent.

The primary outcome was infection after biopsy (including uncomplicated and complicated genitourinary infection and urosepsis) that was independently ascertained with a 7-day survey and by medical record review; secondary outcomes included high-grade cancer (Gleason grade group ≥2) and noninfectious complications.

The analyses were performed using R version 4.2.2 (R Foundation for Statistical Computing) and P < .05 was considered significant.

Results

From February 2021 through March 2024, 875 patients were randomized (Figure); 372 underwent biopsy in the transperineal group vs 370 in the transrectal group. In the intent-to-treat analysis, there were no infections in transperineal group vs 6 infections (grade 2+; 1.6%) in the transrectal group (difference, −1.6% [95% CI, −3.5% to −0.3%; P = .02) (Table). The rates of other complications were low and similar. High-grade cancer was detected in 55% of patients in the transperineal group vs 52% in the transrectal group (difference, 2.9% [95% CI, −4.1% to 9.8%]; P = .40).

Figure. Trial Flow Diagram.

MRI indicates magnetic resonance imaging.

Table. Adverse Events.

Adverse event	No. (%)		Between-group difference (95% CI), %a	P valueb
	Transperineal biopsy (n = 372)	Transrectal biopsy (n = 370)
Infection (grade 2+)	0	6 (1.6)	−1.6 (−3.5 to −0.3)	.02
Required intervention
Urinary retention	1 (0.3)	4 (1.1)	−0.8 (−2.5 to 0.6)	.20
Bleeding	0	1 (0.3)	−0.3 (−1.5 to 0.8)	.50
Gleason grade group
1	57 (15)	68 (18)	−3.1 (−8.6 to 2.4)	.30
2-5c	203 (55)	192 (52)	2.9 (−4.1 to 9.8)	.40

^a Adjusted for site and calculated using logistic regression.

^b Calculated using the Fisher exact test.

^c Considered high-grade cancer groups.

Discussion

Transperineal biopsy had similar cancer detection rates as transrectal biopsy, but there were no infections after transperineal biopsy. Our findings are consistent with other cumulative series³ of transperineal biopsies (>1000) that did not observe infectious complications. Antibiotics are a limited resource; transperineal biopsy enables the exclusion of antibiotic prophylaxis, thereby improving antibiotic stewardship.

The single-center ProBE-PC trial⁴ did not demonstrate differences in the infection rate between transperineal biopsy without prophylaxis vs transrectal biopsy with augmented prophylaxis, but may have captured infections that were not related to the biopsy. This contrasts with the specific, biopsy-related infection definition used in the current trial. The current trial tracked until 7 days after biopsy (usual timeframe for biopsy-related infection) and excluded patients with recent prostatitis (may increase the risk of infection after biopsy), whereas the ProBE-PC trial⁴ used a 30-day outcome and did not exclude patients with recent prostatitis.

The infection rate of 1.6% in the transrectal group in the current trial is lower than rate of 5% to 7% for augmented prophylaxis,⁵ although similar to the rate of 1.9% from a study of targeted transrectal prophylaxis.⁶

There are limitations to this study that should be interpreted in the context of the study design. First, we studied only first-time biopsy and the risk of infection for repeat biopsy in prior negative and active surveillance settings remains understudied. Second, patients who were randomized but did not undergo biopsy were excluded from the intent-to-treat analysis because they are not at risk for biopsy-related infection. Third, we studied targeted rather than augmented prophylaxis because it is more rigorous; however, the majority of transrectal biopsies are performed with augmented prophylaxis.

Transperineal biopsy significantly lowers the risk of infectious complications vs transrectal biopsy. Transperineal biopsy should be the standard of care for prostate biopsy.

Supplement 1.

Trial protocol

Supplement 2.

Data sharing statement