Review Articles

www.auajournals.org/journal/juro

Nonantibiotic Strategies for the Prevention of Infectious

Complications following Prostate Biopsy: A Systematic Review
and Meta-Analysis
Benjamin Pradere,* Rajan Veeratterapillay,* Konstantinos Dimitropoulos, Yuhong Yuan,
Muhammad Imran Omar, Steven MacLennan, Tommaso Cai, Franck Bruye
re, Riccardo Bartoletti,
€ ves, Florian Wagenlehner, Gernot Bonkat and Adrian Pilatz†
Bela Ko
From Urologie (BP, FB), CHRU Bretonneau, Tours, France, Universite  Francois Rabelais (BP, FB), PRES Centre Val de Loire, Tours, France, Freeman Hospital (RV),
Newcastle upon Tyne, United Kingdom, Department of Urology (KD), Aberdeen Royal Infirmary, Aberdeen, Scotland, United Kingdom, Department of Medicine (YY),
Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada, Guidelines Office (MIO), European Association of Urology, Arnhem, The Netherlands,
Academic Urology Unit (SM), University of Aberdeen, Aberdeen, United Kingdom, Department of Urology (TC), Santa Chiara Regional Hospital, Trento, Italy,
Department of Translational Research and New Technologies (RB), University of Pisa, Pisa, Italy, Department of Urology (BK), South-Pest Teaching Hospital, Budapest,
Hungary, Department of Urology (FW, AP), Pediatric Urology and Andrology, Justus-Liebig-University Giessen, Giessen, Germany, and Alta Uro AG (GB), Merian Iselin
Klinik, Center of Biomechanics & Calorimetry, University of Basel, Basel, Switzerland

Purpose: We identify which nonantibiotic strategies could reduce the risk of

Abbreviations
infectious complications following prostate biopsy.
and Acronyms
Materials and Methods: We performed a literature search on MEDLINEÒ,
GRADE [ Grades of Recommen-
EmbaseÒ and the Cochrane Database for randomized controlled trials (inception dation, Assessment, Development
to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary and Evaluation
outcome was pooled infectious complications (fever, sepsis and symptomatic
MA [ meta-analysis
urinary tract infection) and secondary outcome was hospitalization. Cochrane
risk of bias tool and GRADE approach were used to assess the bias and the MRI [ magnetic resonance
imaging
certainty of evidence. The study protocol was registered with PROSPERO
(CRD42015026354). PPNB [ periprostatic nerve block
Results: A total of 90 randomized controlled trials (16,941 participants) were RCT [ randomized controlled
included in the analysis, with 83 trials being categorized into one of 10 different trial
interventions. Transperineal biopsy was associated with significantly reduced RoB [ risk of bias
infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI
0.33e0.92, p[0.02, I2[0%, 1,330 participants, 7 studies). Rectal preparation Accepted for publication July 2, 2020.
* Equal study contribution.
with povidone-iodine was also shown to reduce infectious complications (RR 0.50, † Correspondence: Department of Urology,
95% CI 0.38e0.65, p <0.000001, I2[27%, 1,686 participants, 8 studies) as well as Pediatric Urology and Andrology, Justus Liebig
hospitalization (RR 0.38, 95% CI 0.21e0.69, p[0.002, I2[0%, 620 participants, 4 University Giessen, Rudolf-Buchheim-Str. 7,
35392 Giessen, Germany (telephone: þ49-641-
studies). We found no difference in infectious complications/hospitalization for 6 985-56362; FAX: þ49-641-985-44577; email:
other interventions, ie number of biopsy cores, periprostatic nerve block, number adrian.pilatz@chiru.med.uni-giessen.de).
of injections for periprostatic nerve block, needle guide type, needle type and
rectal preparation with enema. In 2 interventions (needle diameter, rectal
preparation with chlorhexidine) meta-analysis was not possible. Finally, 7
studies had unique interventions. The certainty of evidence was rated as low/
very low for all interventions.
Conclusions: Transperineal biopsy significantly reduces infectious complications
compared to transrectal biopsy and should therefore be preferred. If transrectal
biopsy is performed, rectal preparation with povidone-iodine is highly recom-
mended. The other investigated nonantibiotic strategies did not significantly
influence infection and hospitalization after prostate biopsy.

Key Words: prostate, biopsy, infections, antibiotic prophylaxis

0022-5347/21/2053-0653/0 https://doi.org/10.1097/JU.0000000000001399
THE JOURNAL OF UROLOGY® Vol. 205, 653-663, March 2021
Ó 2021 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. Printed in U.S.A.

www.auajournals.org/jurology j 653
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654 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY
IN 2019 more than 190,000 new cases of prostate
cancer were diagnosed in the United States, causing
more than 33,000 deaths.1 Worldwide, prostate
cancer accounts for a significant proportion of male
cancer and mortality. Prostate cancer diagnosis is
based on biopsies following patient evaluation for an
elevated prostate specific antigen or abnormal dig-
ital rectal examination and there is an increasing
role for pre-biopsy MRI.2,3 Prostatic biopsy remains
the keystone for diagnosis and management of
prostate cancer and the most commonly performed
diagnostic procedure in urology with more than 2
million per year.4 Therefore, many efforts have been
made to prevent infectious complications which ac-
count for the major adverse events with up to 7% of
infections and 3.1% of sepsis depending on antibiotic
prophylaxis regimens.3 Even if an antibiotic pro-
phylaxis is recommended by every guideline, the
incidence of infectious complications is not negli-
gible and its prevention of utmost importance.2,3 In
addition, both the induction of resistance through
the use of antibiotics and side effects must be
considered.5 Post-biopsy infections have been
increasing over the last few years.6,7 Thus, anti-
biotic interventions such as targeted antibiotic
prophylaxis based on rectal swab culture as well as
augmented antibiotic prophylaxis applying more
than 1 antibiotic were introduced to reduce infec-
tious complications.8,9 In a comprehensive meta-
analysis we have recently compiled the evidence of
various interventions for antibiotic prophylaxis.10
In addition to antibiotics different aspects and mo-
dalities of biopsy techniques have been investigated
with a view to minimizing adverse events. Among
them, biopsy route, enema, and number of cores
have been suggested as potential factors to reduce
the infectious risk.11,12 Nevertheless, no systematic
analysis is available evaluating various technical
aspects of prostate biopsy for reducing post-biopsy
infections.
The aim of our comprehensive systematic review
and meta-analysis was to investigate whether and
to what extent any nonantibiotic interventions
reduce the risk of infectious complications following
prostate biopsy.
MATERIALS AND METHODS
Evidence Acquisition
We followed the PRISMA (Preferred Reporting Items
for Systematic Reviews and Meta-Analysis) guidance
and the Cochrane Handbook for systematic reviews
of interventions.13,14 The protocol was registered at
PROSPERO (CRD42015026354). The detailed PICO
(Population, Intervention, Comparison and Outcomes)
is provided in supplementary Appendix 1 (https://www.
jurology.com).
Copyright © 2021 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.
Literature Search
The Medline, Embase, LILACS, CENTRAL, Cochrane
Database of Systematic reviews databases and Clinical-
Trial.gov were searched for randomized controlled trials
(last search May 27, 2020). The grey literature was
searched through opengrey.eu and oclc.org. Potentially
eligible trials were also identified by searching the refer-
ence lists of trials, reviews, and health technology
assessment reports (YY). There were no date or language
restrictions. In order to avoid publication bias, abstracts
characterized as RCTs, but for which published manu-
scripts were not yet available, were included in this sys-
tematic review with meta-analysis, as were funnel plots
for interventions involving more than 10 studies. The
search strategy is included in supplementary Appendix 2
(https://www.jurology.com).
Types of Outcome Measures
Primary Outcome. Pooled infectious complications
(calculated by summing all types of infectious complica-
tions reported ie, fever, sepsis, symptomatic urinary tract
infection). This approach was chosen since in many
studies investigating post-biopsy complications, a
distinction between severe infections (eg sepsis) and
mild infections (eg cystitis) is not reported in detail
(supplementary table 1, https://www.jurology.com).
Secondary Outcome. Hospitalization due to infectious
complications.
Data Collection and Analysis
Abstract screening, full-text screening, and data extrac-
tion was independently performed by 2 reviewers (AP, BP
or RV). For each disagreement, another reviewer (MIO,
SM) was consulted. All the study authors were contacted
to provide missing information if necessary. Eight non-
English articles were evaluated in the corresponding
languages by members of the author team with appro-
priate language skills (4Chinese: YY; 1French: BP, FB;
1Spanish: AP, BP; 2Turkish: Mete Cek, former EAU
Guideline panel member). One Japanese article and 2
Korean articles were translated into English by profes-
sional translators. Among the 90 RCTs there were also 8
studies that have so far only been published as abstracts.
The risk of bias was independently assessed by 2 re-
viewers (RV, KD), by using the Cochrane RoB assessment
tool.14,15 Any disagreements were resolved via discussion
or consultation with another reviewer (MIO, SM). The
GRADE approach was used to assess the certainty of ev-
idence for each comparison (MIO, SM).14
Statistical Analysis
The meta-analysis was performed using Review Manager,
version 5.3. A fixed effects model was used to calculate
pooled estimates of treatment effects across similar
studies and their 95% confidence intervals. We used risk
ratio for dichotomous outcomes. We identified heteroge-
neity by visually inspecting forest plots and using a
standard chi-square test with a significance level of
a[0.1. We also considered the I2 statistic, which quan-
tifies inconsistency across trials to assess the impact of
heterogeneity on the meta-analysis. Where there was
evidence of heterogeneity, we attempted to determine
 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY
possible reasons by examining individual trial, subgroup
characteristics, or by using a random effects model.14
RESULTS
Literature Search and Characteristics of
Included Studies
We identified 3,111 citations, of which 284 were
selected for full-text screening. Reasons for exclu-
sion are provided in supplementary table 2 (https://
www.jurology.com). A total of 90 RCTs were
included in the systematic review (supplementary
Appendix 3, https://www.jurology.com). The inclu-
sion process is graphically illustrated in a PRISMA
diagram (fig. 1). For all included studies we provide
detailed study characteristics in supplementary
table 3 (https://www.jurology.com). Of the 90 RCTs
83 studies could be categorized into one of 10
different interventions, while 7 studies had unique
interventions. Sensitivity analyses for the individ-
ual interventions showed that no changes occurred
with or without the data of the 8 included abstracts
which have not yet been published as full-text.
Risk of Bias Assessment
The RoB assessment is graphically illustrated in
figure 2. It is noticeable that the majority of studies
have an unclear RoB regarding random sequence
Figure 1. Preferred Reporting Items for Systematic Reviews and
Meta-Analyses flowchart.
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655
generation, allocation concealment and blinding of
outcome assessment. Furthermore, most studies
have been conducted without blinding patients or
personnel, which is certainly also due to the type of
technical intervention. A funnel plot from the in-
terventions with more than 10 studies (PPNB)
showed no asymmetry (supplementary Appendix 4,
https://www.jurology.com).
Study Heterogeneity
The I2 statistic was 0% in all cases except Inter-
vention 8 (povidone-iodine), where it was 27%. Since
the p values changed only marginally when using
random effect models for all interventions and end
points, we used fixed effect models throughout.
GRADE
The certainty of evidence was mainly downgraded
due to study design, imprecision and risk of bias
(supplementary Appendix 5, https://www.jurology.
com).
Intervention 1: Impact of Biopsy Route
A total of 7 RCTs including 1,330 patients compared
the impact of biopsy route on infectious complica-
tions (supplementary Appendix 3, https://www.
jurology.com). There were significantly lower infec-
tious complications when the transperineal route
was performed (22 events among 673 men)
compared to the transrectal route (37 events among
657 men; RR 0.55, 95% CI 0.33e0.92, 1,330 partic-
ipants, 7 studies; I2[0%, low certainty; fig. 3).
Data on hospitalization were reported in 3
studies with a total of 685 patients. While 2 hospi-
talizations were necessary in 346 patients in the
transperineal group, hospitalization was reported in
6 cases out of 339 patients undergoing transrectal
biopsy without any statistical difference (RR 0.38,
95% CI 0.09e1.61, 685 participants, 3 studies;
I2[0%, very low certainty; supplementary fig. 1,
https://www.jurology.com).
Intervention 2: Impact of Number of Biopsy Cores
The impact of the number of cores was evaluated in
11 studies including 2,626 men undergoing prostate
biopsy (supplementary Appendix 3, https://www.
jurology.com). While 10 studies performed trans-
rectal biopsy 1 study used the transperineal
approach. MA showed 38 infectious complications in
1,320 men randomized to standard and 47 of those
1,306 randomized to extended number of cores. The
comparison was not significant (RR 0.80, 95% CI
0.53e1.22, 2,230 participants, 9 studies; I2[0%, low
certainty; fig. 4).
Of those studies only 5 presented data on hospi-
talization following prostate biopsy. There was 1
case of hospitalization among 415 men in the stan-
dard group, while 4 cases occurred among 411 men
656 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY
Figure 2. Risk of bias assessment. A, risk of bias summary
according to judgment of review authors on each risk of
bias item for each study included. B, risk of bias graph
according to judgment of review authors for each risk of
bias item presented as percentage across all studies
included.
Copyright © 2021 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.
in the extended biopsy scheme group. The comparison
was not significant (RR 0.34, 95% CI 0.05e2.13, 306
participants, 2 studies; I2[0%, very low certainty;
supplementary fig. 2, https://www.jurology.com).
Intervention 3: Impact of Periprostatic Nerve Block
Pain after periprostatic nerve block during biopsy
was evaluated in 41 RCTs and infectious outcomes
were reported in a total of 5,540 men (supplemen-
tary Appendix 3, https://www.jurology.com). There
were 61 infectious complications among 2,633 pa-
tients randomized to periprostatic nerve block and
73 among 2,907 patients randomized to no nerve
block/control. The comparison was not significant
(RR 1.07, 95% CI 0.77e1.48, 3,857 participants, 26
studies; I2[0%, very low certainty; fig. 5).
Among these studies, only 14 reported hospitali-
zation with 13 cases of hospitalization among 971
men in the PPNB group, while 15 cases occurred
among 1,128 men in the group without PPNB. The
comparison was not significant (RR 1.13, 95% CI
0.59e2.16, 1,469 participants, 9 studies; I2[0%,
very low certainty; supplementary fig. 3, https://
www.jurology.com).
Intervention 4: Impact of Number of Injections for
Periprostatic Nerve Block
Six studies compared the number of injections
applied for PPNB and assessed post-biopsy in-
fections (supplementary Appendix 3, https://www.
jurology.com). MA showed 5 infections among 459
men randomized to standard number of injections
and 4 among 468 men randomized to extended
PPNB. The difference was not statistically signifi-
cant (RR 1.30, 95% CI 0.35e4.76, 478 participants, 3
studies; I2[0%, low certainty; supplementary fig. 4,
https://www.jurology.com).
Two studies reported hospitalization with 2 pa-
tients being hospitalized among 147 men randomized
to standard PPNB and 2 men among 153 randomized
to extended PPNB. The difference was not statisti-
cally significant (RR 1.05, 95% CI 0.15e7.32, 300
participants, 2 studies; I2[0%, low certainty; sup-
plementary fig. 5, https://www.jurology.com).
Intervention 5: Impact of Disposable
Needle Guides
Two RCTs evaluated the use of disposable needle
guides compared to reusable guides in a total of 253
patients (supplementary Appendix 3, https://www.
jurology.com). There were 9 events among 113
men randomized to disposable needle guides and 22
events among 140 men randomized to reusable
needle guides. The difference was not statistically
significant (RR 0.51, 95% CI 0.24e1.06, 253
 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY 657

Figure 3. Comparison of transperineal to transrectal biopsy on infectious complications following prostate biopsy. M-H, Mantel-Haenszel
method.

participants, 2 studies; I2[0%, very low certainty;
supplementary fig. 6, https://www.jurology.com).
Both studies evaluated the impact on hospitali-
zation. While 4 events occurred in 113 men ran-
domized to the disposable needle guide group, 9
events were recorded in 140 men of the reusable
needle guide group. The difference was not statis-
tically significant (RR 0.55, 95% CI 0.17e1.74, 253
participants, 2 studies; I2[0%, very low certainty;
supplementary fig. 7, https://www.jurology.com).
Intervention 6: Impact of Needle Type
Only 2 studies investigated the impact of a co-
axial needle versus a noncoaxial needle and re-
ported on infectious complications (supplementary
Appendix 3, https://www.jurology.com). Data anal-
ysis revealed no infections in 171 men in the coaxial
needle arm, while 1 case occurred among 171 men in
the group randomized to the noncoaxial biopsy
needles. MA was not possible because of zero events
in 1 study. Hospitalization was reported in only 1 of

Figure 4. Comparison of standard to extended biopsy cores on infectious complications following prostate biopsy. Note: Emilozzi 2004
reports transperineal biopsy, while all other studies performed transrectal biopsy. M-H, Mantel-Haenszel method.

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658 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY

Figure 5. Effect of periprostatic nerve block on infectious complications following prostate biopsy. M-H, Mantel-Haenszel method.

the 2 studies and did not occur in any among the study. Hospitalization was not reported as an end
240 patients. point in any study.

Intervention 7: Impact of Needle Diameter Intervention 8: Impact of Rectal Preparation

The impact of needle diameter was investigated in 2
studies (supplementary Appendix 3, https://www.
jurology.com). Data analysis revealed no infections
in 133 men randomized to the smaller needle
diameter, while 1 case occurred among 163 men in
the group randomized to the larger needle diameter.
MA was not possible because of zero events in one
with Enema
Four RCTs evaluated rectal preparation with
enema (supplementary Appendix 3, https://www.
jurology.com). Among 336 men randomized to
enema 30 events were recorded, while among 335
men in control group 31 events were reported. The
difference was not statistically significant (RR 0.96,

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 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY 659

Figure 6. Effect of rectal preparation with enema on infectious complications following prostate biopsy. M-H, Mantel-Haenszel method.

95% CI 0.60e1.53, 671 participants, 4 studies;
I2[0%, low certainty; fig. 6).
Only 2 studies with 231 patients per group re-
ported on hospitalization with 9 events in the enema
and 8 events in the control group. This comparison
was not statistically significant (RR 1.13, 95% CI
0.44e2.86, 462 participants, 2 studies; I2[0%, low
certainty; supplementary fig. 8, https://www.
jurology.com).
Intervention 9: Impact of Rectal Preparation
with Chlorhexidine
Two studies investigated the influence of rectal
preparation with chlorhexidine (supplementary Ap-
pendix 3, https://www.jurology.com). Although both
studies report infectious complications separately for
the intervention and control groups, the primary
outcome cannot be meta-analyzed due to a possible
double case count in one of the studies.
Intervention 10: Impact of Rectal Preparation
with Povidone-Iodine
Nine studies evaluated the use of rectal preparation
with povidone-iodine (supplementary Appendix 3,
https://www.jurology.com) in a total of 1,936 pa-
tients. MA showed 61 infections among 930 men in
the povidone-iodine group and 131 among 1,006 in
the control group. The difference was statistically
significant (RR 0.50, 95% CI 0.38e0.65; 1,686 par-
ticipants, 8 studies; I2[27%, low certainty; fig. 7).

Figure 7. Effect of rectal preparation with povidone-iodine on infectious complications following prostate biopsy. M-H, Mantel-Haenszel
method.

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660 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY
Figure 8. Effect of rectal preparation with povidone-iodine on hospitalization following prostate biopsy. M-H, Mantel-Haenszel method.
Four studies reported on hospitalization with a
total of 12 men hospitalized among 285 men ran-
domized to povidone-iodine preparation and 37 men
among 335 randomized to the control group. The
difference was statistically significant (RR 0.38, 95%
CI 0.21e0.69, 620 participants, 4 studies; I2[0%,
low certainty; fig. 8).
Different Unique Interventions
Seven RCTs with unique technical interventions (eg
needle disinfection, needle size, perineal cleansing)
were identified. Of those, only 1 study investigating
the time point of rectal preparation with povidone-
iodine showed significantly reduced infectious com-
plications when applied before vs after biopsy (see
Appendix).
DISCUSSION
To our knowledge this meta-analysis is the first to
assess all the different technical aspects of prostate
biopsy that can possibly reduce the risk of infec-
tious complications. Therefore, it complements our
comprehensive previous meta-analysis on antibiotic
prophylaxis of prostate biopsy.10 In the current
analysis we have reported a total of 90 RCTs
exploring nonantibiotic prophylactic strategies
including the risk of peri-prostatic nerve block,
prostate biopsy route, number of cores, rectal prep-
aration, and type of needle used. Among the
different strategies assessed in our analysis, trans-
perineal prostate biopsy route and rectal prepara-
tion with povidone-iodine were found as the best
interventions (low certainty of evidence) to reduce
both post-biopsy infections and hospitalization.
This meta-analysis is the most comprehensive and
recent one evaluating specifically infectious compli-
cations in the head-to-head comparison between
transperineal and transrectal route. The 2 ap-
proaches have been highly debated in recent years
Copyright © 2021 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.
with the introduction of MRI targeted biopsy and
diagnostic accuracy.16e20 In addition, there is
increasing evidence that MRI diagnostics can be
used to avoid unnecessary prostate biopsiesdand
thus the corresponding complications.21,22 Until now,
the different MRI targeted biopsy methods have not
proved a real significant difference in terms of pros-
tate cancer detection.23,24 The most recent studies
were designed to assess prostate cancer detection
rates between the 2 techniques and the potential risk
for adverse events was only a secondary crite-
rion.25,26 Hence, study size of the aforementioned
studies was not calculated to reveal differences in
post-biopsy infection, but to investigate diagnostic
accuracy. Thus, 2 older meta-analyses evaluating
also infectious complications in dependence of the
biopsy route did not report a significant differ-
ence.12,27 On the other hand, a recent meta-analysis
suggested a benefit of transperineal biopsy, which
significantly protected patients from postoperative
fever (RR 0.26, 95% CI 0.14e0.28).28 However, all 3
of these meta-analyses are limited because they
combined estimates from RCTs with those from case-
control studies and double counted 1 study published
in duplicate, which has a very low number of post-
biopsy infections in both groups.29,30
In the largest systematic review on infectious
complications following prostate biopsy (165 studies
including 162,577 patients) the standardized preva-
lence of sepsis was 0.8% in transrectal and 0.1% in
transperineal biopsy and the standardized prevalence
of hospitalization was 1.1% vs 0.9%, respectively.31
These data are not surprising, as they reinforce the
classical principle for a surgical procedure to choose
the lowest possible contamination category in order to
reduce the rate of infectious complications.32 Our
meta-analysis based on 7 RCTs confirmed this
important aspect and showed a significantly lower
infection rate using the transperineal route (RR 0.55,
 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY 661

95% CI 0.33e0.92). Despite the potential logistic

Lower complications in intervention group, but not statistically significant

Lower complications in intervention group, but not statistically significant

Lower complications in intervention group, but not statistically significant

challenges attached to the widespread introduction of

Significantly reduced infectious complications in groups with rectal

the local anesthetic transperineal technique, our
findings support the “TREXIT 2020” approach to
abandon transrectal prostate biopsy.17
Another important aspect is the number of bi-

Infectious complications not significantly different*

Infectious complications not significantly different†

Infectious complications not significantly different
opsy cores taken. Over the years, the number has
increased with the aim of improving diagnostic
accuracy. Since one passes repeatedly through the

Outcome
rectal mucosa by an increased number of biopsy
cylinders, one would expect a higher infection
rate. Various cohort studies addressed this

preparation before biopsy

important point and were mainly able to show
that the number of biopsy cylinders obtained is
independent of postoperative infections.33e35 Our
meta-analysis including 11 RCTs shows that the
number of cores is not associated with the risk of
infection. This confirms the current guidelines
which recommend standard biopsies in addition to
targeted biopsies.2,3
In this context, the question of local anesthesia in
the sense of a periprostatic nerve block arises. Various
meta-analyses could impressively show that the peri-
prostatic nerve block significantly contributes to peri-
operative pain control compared to an anesthetic gel

Time point of rectal preparation with povidone-iodine (before vs after vs before plus after)
applied intrarectally/control.36e39 However, this re-
Rectal preparation with povidone-iodine plus formalin needle disinfection vs control

quires further passages of a needle through the rectum

and the injection of an anesthetic might be associated
with the risk of distribution of possible pathogens.
Transperineal prostatic nerve block vs transrectal periprostatic nerve block

Perineal cleansing vs no perineal cleansing in transrectal prostate biopsy

Previous meta-analyses on this topic reported

sporadically on post-biopsy infections, but never pri-
marily investigated the impact of periprostatic nerve
block on infection.38,39 Our analysis including 41 RCTs
could show that there is no increased risk of infection
using periprostatic nerve block. In addition, the
Intervention

Needle washing with povidone-iodine vs control

number of injections used for the periprostatic nerve

PPNB plus intraprostatic injection vs control

block has no impact on the rate of post-biopsy in-

fections. This is absolutely consistent with the number
† Raw data provided from authors; urosepsis 1 vs 1; hospitalization 1 vs 1.

of biopsy cores taken as discussed above, which had no

* Raw data provided from authors; febrile urinary tract infection: 3 vs 2.
Enema vs full bowel preparation

influence on the infection rate.

Since the passage of the needle leads through the
contaminated rectal mucosa, there are several studies
that have investigated different parameters of the
needle. The diameter, shape, disinfection and the
nature of the needle guide were each investigated in 1
or 2 studies, but no significant advantage in pre-
venting post-biopsy infection was ever detected.40e45
Rectal preparation is a heterogenous practice when
transrectal biopsies are planned with some urolo-
gists using enema, chlorhexidine, povidone-iodine
Appendix. Unique RCTs

applications, full bowel preparation, or no preparation

at all. Here, we found that enema had no impact on
postoperative infectious complications. However, rectal
De Nunzio 2015
Study and Year

preparation with povidone-iodine prior to prostate bi-

Bingqian 2009

Costa 2019

Taher 2014
Bolat 2016

opsy significantly reduced the risk of infection (RR 0.50,

Koc 2010

Yu 2015

95% CI 0.38e0.65), and hospitalization (RR 0.38, 95%

CI 0.21e0.69). This is fully in line with a previous meta-

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662 TECHNICAL INTERVENTIONS TO REDUCE INFECTION AFTER PROSTATE BIOPSY

analysis.11 The advantages of rectal povidone-iodine
preparation are its simple implementation to daily
practice without largely increasing the cost of the pro-
cedure.46 Despite the clear recommendation in guide-
lines,2 the value still needs to be spread among
urologists.33
The major strengths of this systematic review are
that, 1) it is the most comprehensive analysis on
nonantibiotic prophylaxis strategies to prevent infec-
tious complications after prostate biopsy, 2) we
included only RCTs without any language and publi-
cation date restriction, 3) it also includes studies with
patients being at higher risk for post-biopsy infection,
and 4) it reports with post-biopsy infections and hos-
pitalization due to infection the 2 most important
adverse events after prostate biopsy.
Our study has some limitations that should be
acknowledged. 1) All infections were summed, since
in many included studies a distinction between se-
vere infections (eg sepsis) and mild infections (uri-
nary tract infection) were not reported in detail,
2) many RCTs were not designed for the evaluation
of postoperative complications particularly regarding
peri-prostatic nerve block, which might underesti-
mate infections and leads to a possible bias, 3) our
analysis has been done without taking the individual
antibiotic prophylaxis regimes used in each study
into account, as I2 was low or very low in all in-
terventions, and 4) as it was the evaluation of
nonantibiotic measures, the geographical origin of
the included RCTs was not considered.
CONCLUSIONS
In this systematic review and meta-analysis we
evaluated all published nonantibiotic prophylaxis
regimens to reduce infectious complications following
prostate biopsy. We show with low certainty of evi-
dence, that both transperineal biopsy and rectal
preparation with povidone-iodine in transrectal bi-
opsy significantly reduce the risk of infection.
Whereas many concerns are rising to reduce anti-
biotic resistance and side effects, these nonantibiotic
procedures should be favored in daily practice.
ACKNOWLEDGMENTS
Emma Smith from the EAU Guidelines Office
assisted with the systematic review, and Robert
Pickard (deceased), Newcastle upon Tyne, United
Kingdom, initiated this review.

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