www.auajournals.
org/journal/juro
The Effect of Different Types of Prostate Biopsy Techniques on
Post-Biopsy Infectious Complications
Sofie C. M. Tops, Justin G. A. Grootenhuis, Anouk M. Derksen et al.
Correspondence: Sofie C. M. Tops (email: sofie.tops@radboudumc.nl).
Full-length article available at auajournals.org/10.1097/JU.0000000000002497.
Study Need and Importance: Infection rates after
transrectal prostate biopsy (PB) are rising due to
growing numbers of fluoroquinolone-resistant rectal
flora. Alternatives must be sought as these infections
can be severe and lead to sepsis. We compared in-
fectious complication rates between different PB
techniques with various number of biopsy cores.
What We Found: In total, 4,233 PBs in 3,707 patients
were included. After transrectal ultrasound-guided
PB (TRUSPB; 12
1.4 biopsy cores), 4.0% (2,607) of
all patients had infectious complications within 7 days
post-biopsy. Transperineal magnetic resonance imag-
ing (MRI)-ultrasound fusion guided PB (16
3.7 bi-
opsy cores) was associated with significantly lower
infection rates than TRUSPB (adjusted OR: 0.29
[0.09e0.73] 95% CI). Transrectal targeted MRI-
ultrasound fusion guided PB (3.1
0.8 biopsy cores)
and transrectal targeted in-bore MRI guided PB
(2.8
0.8 biopsy cores) also showed fewer infectious
complications than TRUSPB (adjusted OR: 0.41
[0.12e1.12] 95% CI and 0.68 [0.37e1.20] 95% CI,
respectively). Similar results were found for infectious
Table. Main findings
Transrectal Ultrasound-Guided
PB
Targeted Biopsies 10
Biopsy Cores
% Infectious complications within 7 4.0 (104)
days post-biopsy (No.), adjusted OR
(95% CI)
% Infectious complications within 30 4.8 (125)
days post-biopsy (No.), adjusted OR
(95% CI)
% Hospitalization within 7 days post- 2.8 (73)
biopsy (No.)
% Bacteremia within 7 days post-biopsy 1.0 (25)
(No.)
TRUS, transrectal ultrasound.
THE JOURNAL OF UROLOGY®
Ó 2022 The Author(s). Published on behalf of the
American Urological Association, Education and Research, Inc.
JU Insight
complications within 30 days post-biopsy, hospitali-
zation and bacteremia (see Table). Prophylaxis-
resistant bacteria were found in 62% and 78% of the
bacteria isolated from urine cultures of patients
within 7 and 30 days post-biopsy, respectively.
Limitations: Differences in the risk of infectious
complications when taking different numbers of bi-
opsy cores in transperineal PB were not assessed. Due
to the retrospective nature of our study, some post-
biopsy infections might have been missed. However,
we do not expect this to differ between the cohorts.
Implications for Patient Care: Post-biopsy infections
can be reduced using a transperineal approach.
Reducing the number of biopsy cores by using a
transrectal targeted PB only approach could be a
reasonable alternative. Diagnostic accuracy should
be decisive here. In view of the high percentage of
prophylaxis-resistant bacteria isolated from post-
biopsy urine cultures, culture-based prophylaxis
could potentially also contribute to the reduction of
infectious complications.
Transrectal Targeted MRI-TRUS Transrectal Targeted In-Bore Transperineal MRI-TRUS
Fusion or TRUSPB 4 Biopsy MRI-Guided PB 4 Biopsy Fusion Guided PB 10 Biopsy
Cores Cores Cores
1.0 (4), 0.41 (0.12e1.12) 2.1 (19), 0.68 (0.37e1.20) 1.3 (4), 0.29 (0.09e0.73)
1.3 (5), 0.42 (0.14e1.04) 2.3 (21), 0.58 (0.33-0.99) 2.6 (8), 0.46 (0.19e0.96)
0.3 (1) 1.2 (11) 0.0 (0)
0.3 (3) 0.0 (0) 0.0 (0)
https://doi.org/10.1097/JU.0000000000002497
Vol. 208, 109-118, July 2022
Printed in U.S.A.
www.auajournals.org/jurology j 109
 www.auajournals.org/journal/juro

The Effect of Different Types of Prostate Biopsy Techniques on

Post-Biopsy Infectious Complications
Sofie C. M. Tops,1*† Justin G. A. Grootenhuis,2† Anouk M. Derksen,3 Federica Giardina,4
Eva Kolwijck,1,5 Heiman F. L. Wertheim,1 Diederik M. Somford3† and J. P. Michiel Sedelaar2†
1
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
2
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands
3
Department of Urology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
4
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands
5
Department of Medical Microbiology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

Abbreviations
and Acronyms
mpMRI [ multiparametric mag-
netic resonance imaging
MRI [ magnetic resonance
imaging
PB [ prostate biopsy
TPFUSPB [ transperineal MRI-
ultrasound fusion guided PB
TRFUSPB [ transrectal targeted
MRI-ultrasound fusion guided PB
TRMRIPB [ transrectal targeted
in-bore MRI guided PB
TRUSPB [ transrectal
ultrasound-guided prostate biopsy
(
additional targeted biopsies)
UTI [ urinary tract infection
Purpose: The aim of our study was to compare infectious complication rates be-
tween different prostate biopsy techniques with various number of biopsy cores.
Materials and Methods: In this retrospective study, all patients from 2 hospitals
who underwent prostate biopsy between 2012 and 2019 were identified. Cohorts
with different types of prostate biopsies were compiled within these hospitals.
Primary outcome measure was any registered infectious complication within 7
days post-biopsy. Secondary outcomes were infectious complications within 30
days, hospitalization and bacteremia. To compare the risk of infection following
different prostate biopsy techniques, data was fitted into a logistic regression
model adjusting for potential confounders.
Results: In total, 4,233 prostate biopsies in 3,707 patients were included. After sys-
tematic transrectal ultrasound-guided prostate biopsy (TRUSPB; 12
1.4 biopsy cores),
4.0% (2,607) of all patients had infectious complications within 7 days post-biopsy.
Transperineal magnetic resonance imaging (MRI)-ultrasound fusion guided prostate
biopsy (16
3.7 biopsy cores) was associated with significantly lower infection rates
than systematic TRUSPB (adjusted OR: 0.29 [0.09e0.73] 95% confidence interval
[CI]). Transrectal targeted MRI-ultrasound fusion guided prostate biopsy (3.1
0.8
biopsy cores) and transrectal targeted in-bore MRI guided prostate biopsy (2.8
0.8
biopsy cores) also showed fewer infectious complications than systematic TRUSPB
(adjusted OR: 0.41 [0.12e1.12] 95% CI and 0.68 [0.37e1.20] 95% CI, respectively).
Conclusions: Transperineal prostate biopsy, or transrectal prostate biopsy with
reduced number of biopsy cores, could lower the risk of infectious complications.

Key Words: biopsy, image-guided biopsy, infections, perineum, rectum

Accepted for publication February 17, 2022.

Support: This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw), Grant number 541001009.
Conflict of Interest: None of the contributing authors have any conflicts of interest.
Author Contributions: Study design: ST, EK, MS, DS, HW. Data collection: ST, AD, JG. Data analysis: ST, JG, FG. Writing the manuscript: ST,
JG. Critical review of the manuscript: FG, AD, EK, DS, HW, MS. All authors have read and approved the manuscript.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License
4.0 (CCBY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or
used commercially without permission from the journal.
* Correspondence: Afdeling Medische Microbiologie, huispost 777 Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands (tele-
phone: þ31655757376; FAX: þ31243635153; email: sofie.tops@radboudumc.nl).
† Equal contributors.

Editor’s Note: This article is the third of 5 published in this issue for which Category 1 CME credits can
be earned. Instructions for obtaining credits are given with the questions on pages 226 and 227.

THE JOURNAL OF UROLOGY® https://doi.org/10.1097/JU.0000000000002497

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American Urological Association, Education and Research, Inc. Printed in U.S.A.
110 j www.auajournals.org/jurology
 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES
AN estimated 2 million prostate biopsies (PBs) are
performed worldwide every year, of which trans-
rectal ultrasound-guided biopsy (TRUSPB) is the
most commonly performed to date.1 Transrectal PB
is generally considered a safe procedure; nonethe-
less, it may cause infections due to introduction of
gut bacteria into the prostate, urinary tract or
bloodstream.2,3 Although several classes of antibi-
otics are proven effective for prophylaxis in trans-
rectal PBdwith fluoroquinolones traditionally the
most commonly useddthe risk of post-biopsy in-
fections must be taken very seriously. First, given
the large number of PBs performed, a significant
number of men worldwide are exposed to post-
biopsy infections per year (estimated 110,000).4e6
Second, in the last decades there has been a rise in
infections after PB, which has been linked to
growing numbers of fluoroquinolone-resistant
Escherichia coli, the predominant organism in
post-biopsy infections.7
Various strategies have been proposed to mini-
mize the risk of infections after PB, varying from
antibiotic strategies such as culture-based prophy-
laxis to pre-biopsy rectal preparation with povidone-
iodine reducing the bacterial load.1,2,8e11 Addition-
ally, technical aspects of PB, such as biopsy core
number or biopsy route, might have impact on post-
biopsy infection rates.
Biopsy core number can be reduced by targeting
biopsies to suspicious areas only using multiparametric
magnetic resonance imaging (mpMRI).12e16 Until now,
most studies primarily focused on the diagnostic ac-
curacy of PB and only some subanalyses were reported
with variable results concerning the infectious com-
plications of PB.11,17e22 In addition, a comparison
regarding the risk of infections after transrectal tar-
geted in-bore magnetic resonance imaging (MRI)
guided PB, with a longer procedural- and inoculation
time, and transrectal targeted MRI-ultrasound fusion
guided PB (TRFUSPB) is missing. Importantly,
guidelines still advocate combining targeted and sys-
tematic PB in case of suspicion of prostate cancer in
biopsy naive patients.23
Another strategy to reduce post-biopsy infections
is transperineal PB, avoiding the rectum, which
harbors a higher bacterial load, while maintaining
adequate numbers of biopsy cores.8 Several studies
showed that transperineal PB was associated with
fewer infectious complications than transrectal
PB.11,24 In fact, therefore, some guidelines currently
advise to perform transperineal PB.23
To date, only 1 small study directly compared
infection rates after transrectal PB with reduced
number of biopsy cores and transperineal PB with
the standard number of biopsy cores showing
similar infection rates.17 The aim of our study was
to compare infectious complication rates between
111
different PB techniques with various number of bi-
opsy cores.
PATIENTS AND METHODS
Study Population
In this retrospective cohort study, all patients who un-
derwent PB in the period 2012e2019 at an academic
hospital (hereinafter referred to as hospital A) and a
nonacademic teaching hospital (hereinafter referred to as
hospital B), located in the same city, were identified using
the nationwide network and registry of histo- and cyto-
pathology (PALGA). Search terms used were name pa-
thology report: prostate biopsy, years: 2012-2019,
applicant: urologist. Patients were enrolled in the study if
they met the criteria for one of the cohorts: 1) systematic
transrectal ultrasound-guided PB
additional targeted
biopsies 10 biopsy cores (TRUSPB); 2) TRFUSPB or
TRUSPB 4 biopsy cores (TRFUSPB); 3) transrectal
targeted in-bore MRI guided PB 4 biopsy cores
(TRMRIPB); or 4) transperineal MRI-ultrasound fusion
guided PB 10 biopsy cores (TPFUSPB).
All patients received short-duration antimicrobial
prophylaxis prior to PB according to standard protocols
(ciprofloxacin; supplementary Appendix 1, https://www.
jurology.com). No rectal disinfection with povidone-
iodine was performed. In the TRFUSPB and TRMRIPB
cohorts, all patients underwent mpMRI (T2/DWI/DCE,
no rectal probe was used). Exclusion criteria were lack
of followup, repeat biopsy within 30 days, other uro-
logical intervention within 7 days and no empirical
antimicrobial prophylaxis taken. Ethical approval was
obtained from the local Institutional Review Boards
(IRB No. 2019-5538).
Outcome Measures
Data were retrieved with the use of a data warehouse, an
analytical tool that is able to extract data from electronic
medical records semiautomatically. Electronic medical
records were manually searched for information that was
not retrieved by the data warehouse. Our primary
outcome was any registered infectious complication
within 7 days after PB (Table 1). Secondary outcomes
were any registered infectious complication within 30
days post-biopsy, hospitalization and bacteremia. More-
over, overall antibiotic use and rates of ciprofloxacin-
resistant gram-negative bacteria in microbiological urine
or blood cultures within 30 days post-biopsy were recor-
ded. Potential confounders were documented.
Statistical Analysis
First, to compare the individuals in the different cohorts,
a descriptive statistical analysis was performed contain-
ing proportions, frequencies, medians and interquartile
ranges. Factors compared can be found in Table 2.
In order to check for systematic differences regarding
the risk of infectious complications (primary outcome)
between the 2 hospitals, a logistic regression model was
fitted using only data from the TRUSPB cohort: the only
widely used technique in both hospitals. Then, a logistic
regression model adjusting for potential confounders was
fitted to the entire data set to compare infectious
112 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES
Table 1. Definitions of post-biopsy infectious complications.
Definitive UTI Without systemic symptoms
With systemic symptoms*
Probable UTI Without systemic symptoms
With systemic symptoms*
Acute prostatitis
Acute epididymitis
Sepsis
Severe sepsis
Isolated fever
* Systemic symptoms are defined as: fever, chills, malaise.
complications rates between the different types of PB.
Only known risk factors were included in the model as
potential confounders: 1) a binary variable indicating
whether (baseline) individuals were affected by diabetes
mellitus, 2) a binary variable indicating whether patients
received solely prophylaxis with ciprofloxacin, 3) a binary
variable indicating where the PB was performed (hospital
A or B) and 4) year of PB (2012e2019). A descriptive
analysis was performed to compare the risk of hospitali-
zation and bacteremia (secondary outcomes). All statisti-
cal analyses were done using R version 4.0.3 (R
Foundation for Statistical Computing, Vienna, Austria).25
RESULTS
Characteristics of the Cohorts
The division of patients into the different cohorts
per hospital is depicted in Figure 1. In total, 4,233
PBs were included: 2,277 (54%) in hospital A and
1,956 (46%) in hospital B. These 4,233 PBs were
performed in 3,707 unique patients (supplementary
Appendix 2, https://www.jurology.com).
Characteristics of the patients who underwent the
4,233 PBs per cohort per hospital are depicted in
Table 2. In the TRUSPB cohort, in total, 215 patients
(8.3%) had targeted biopsies (cognitive fusion) in addi-
tion to the standard systematic biopsies. All of these
patients, except for 1, had their PB at hospital B. In the
TRFUSPB cohort, 46 standard transrectal ultrasound-
guided PBs 4 biopsy cores were included (12%; hos-
pital A: 13 PBs and hospital B: 33 PBs). All patients
received antibiotic prophylaxis (fluoroquinolone-based
prophylaxis regimen; 91%; supplementary Appendix
1, https://www.jurology.com).
Infectious Complications within 7 Days
Post-Biopsy
Our main findings are depicted in Table 3. In the
TRUSPB cohort (12
1.4 biopsy cores; 2,607), 4.0%
Symptoms of dysuria, urgency, frequency or hematuria AND pyuria (>5 white blood cells per high power field
or urinary dipstick test that is positive for leukocyte esterase) and/or bacteriuria (103 colony-forming
units/ml)
Symptoms of dysuria, urgency, frequency or hematuria AND symptoms of fever, chills or malaise AND pyuria
(>5 white blood cells per high power field or urinary dipstick test that is positive for leukocyte esterase)
and/or bacteriuria (103 colony-forming units/ml)
Symptoms of dysuria, urgency, frequency or hematuria not proven by urine screening, sediment or culture for
which antibiotics are prescribed
Symptoms of dysuria, urgency, frequency or hematuria AND symptoms of fever, chills or malaise not proven
by urine screening, sediment or culture for which antibiotics are prescribed
Symptoms of fever, chills, malaise, dysuria, urgency, frequency AND pelvic/perineal pain or tender prostate
during palpation of the prostate AND pyuria (>5 white blood cells per high power field or urinary dipstick
test that is positive for leukocyte esterase) and/or bacteriuria (103 colony-forming units/ml)
Presence of a swollen, red or warm scrotum, accompanied by tenderness for which antibiotics are prescribed
Suspicion of infection plus at least 2 of the following criteria (qSOFA score): systolic blood pressure 100
mmHg, respiratory rate 22 breaths per min or Glasgow coma scale <15
Sepsis plus organ dysfunction or with persisting hypotension requiring vasopressors to maintain a mean
arterial pressure 65 mmHg and to have a serum lactate level <2 mmol/L despite adequate volume
resuscitation
Body temperature 38.0C without localizing signs and symptoms
of all patients had an infectious complication
(Figs. 2 and 3). The logistic regressiondcombining
all 4 cohortsdshowed a significantly lower risk of
infectious complications within 7 days after
TPFUSPB (16
3.7 biopsy cores; 311) than after
TRUSPB (adjusted OR: 0.28 [0.08e0.68] 95% CI).
TRFUSPB (3.1
0.8 biopsy cores; 396) and
TRMRIPB (2.8
0.8 biopsy cores; 919) were associ-
ated with a low infection risk compared to TRUSPB
(adjusted OR: 0.40 [0.11e1.07] 95% CI and 0.67
[0.37e1.18] 95% CI, respectively). Infectious com-
plications within 7 days after PB are described in
more detail in supplementary Appendixes 3 and 4
(https://www.jurology.com).
Infectious Complications within 30 Days
Post-Biopsy
Individuals in the TRUSPB cohort had a higher risk
of infectious complications within 30 days post-biopsy
(4.8%) than individuals in the other cohorts. The re-
sults of the logistic regression are shown in Table 3.
Infectious complications within 30 days after PB are
described in more detail in supplementary Appen-
dixes 5 and 6 (https://www.jurology.com).
Hospitalization
In total, 64% of the patients with an infectious
complication within 7 days after PB (132) were
admitted to the hospital for 4.4
2.5 days
(mean
SD). Hospitalization rates within 7 days
post-biopsy are depicted in Table 3. Four patients
(0.15%), all from the TRUSPB cohort, were hospi-
talized for an infectious complication between 8 and
30 days post-biopsy.
Overall Antibiotic Use
Patients with infectious complications within 7 days
after PB (132) received an average of 1.8 antibiotics
Table 2. Patients’ characteristics per cohort per hospital
Hospital A Hospital B

Transrectal Targeted Transrectal Targeted Transrectal Targeted

Transrectal Ultrasound-Guided MRI-TRUS In-Bore Transrectal Ultrasound-Guided MRI-TRUS Transperineal MRI-TRUS
PB
Targeted Biopsies 10 Fusion or TRUSPB 4 MRI-Guided PB 4 PB
Targeted Biopsies 10 Fusion or TRUSPB 4 Fusion Guided PB 10
Biopsy Cores Biopsy Cores Biopsy Cores Biopsy Cores Biopsy Cores Biopsy Cores
No. 995 363 919 1,612 33 311
Mean
SD No. biopsy cores 11
1.0 3.1
0.7 2.8
0.8 12
1.2 3.8
0.6 16
3.7
No. yr of biopsy:
2012 232 5 130 3 6 0
2013 213 4 129 267 4 10
2014 200 17 97 252 5 36

EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES

2015 132 32 87 211 2 36
2016 127 32 79 254 4 55
2017 32 63 127 212 1 63
2018 35 89 148 202 6 57
2019 24 121 122 211 5 54
Median yrs age (Q1eQ3) 66 (61e70) 68 (63e73) 66 (62e70) 67 (62e73) 77 (72e80) 66 (62e71)
Median age-adjusted Charlson Comorbidity 3 (2e4) 3 (2e4) 3 (2e4) 3 (2e4) 4 (3e6) 3 (2e5)
Index (Q1eQ3)
% Prophylaxis with ciprofloxacin 89 (888) 94 (342) 96 (882) 93 (1,492) 76 (25) 71 (222)
monotherapy (No.)
% Previous PB 3 mos (No.) 0.3 (3) 1.1 (4) 5.4 (50) 0.4 (6) 3.0 (1) 7.4 (23)
% Pre-biopsy lower urinary tract 64 (644) 58 (211) 41 (378) 55 (882) 58 (19) 52 (163)
symptoms (No.)
% Symptoms of chronic prostatitis (No.) 7.3 (73) 9.4 (34) 6.5 (60) 7.2 (116) 3.0 (1) 12 (36)
% History of UTI (No.) 15 (150) 9.9 (36) 8.5 (78) 17 (277) 15 (5) 18 (57)
% History of diabetes mellitus (No.) 7.3 (73) 6.9 (25) 5.4 (50) 12 (190) 6.1 (2) 11 (33)
% Immunocompromised (No.) 2.8 (28) 3.9 (14) 1.9 (17) 0.7 (11) 3.0 (1) 0.6 (2)
Median µg/L prostate specific antigen 7.0 (4.9e10.9) (938) 12 (7.0e41.0) (343) 7.9 (5.0e12.0) (781) 7.8 (5.4e12.1) (1,516) 120 (28e827) 8.9 (5.7e13) (174)
(Q1eQ3) (No.) 32
Median cm3 prostate vol measured by MRI 50 (37e71) (331) 56 (39e74) (302) 51 (35e71) (777) 58 (42e75) (535) 58 (53e63) (2) 59 (45e91) (238)
(Q1eQ3) (No.)
Median cm3 prostate vol measured by 59 (42e80) (969) 56 (40e73) (42) 52 (34e72) (11) 51 (37e72) (1,465) 47 (42e71) (14) 57 (38e92) (73)
ultrasound (Q1eQ3) (No.)
% Histopathology pos for malignancy (No.) 47 (466) 79 (288) 66 (610) 51 (826) 97 (32) 64 (200)
Median km straight-line travel distance to 13 (4.9e36) 25 (8.6e61) 45 (16e80) 8.9 (4.0e14) 7.4 (3.7e13) 13 (6.7e35)
hospital (Q1eQ3)

TRUS, transrectal ultrasound.

113
114 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES
Figure 1. Division of patients into the different cohorts. TRUS, transrectal ultrasound.
for a total duration of 16
8.6 days (mean
SD). In 7
patients, the prescribed antibiotics were unknown
and in 22 patients antibiotic duration was
unknown.
Microbiological Outcome Measures
In the 132 patients with infectious complications
within 7 days after PB, 104 urine cultures (79%)
were taken (unknown: 8 patients). In 55 of these 104
urines (53%) one or more relevant microorganisms
were cultured, predominantly E. coli (82%). In 62%
of the urines with known antimicrobial susceptibil-
ity profile (52), a ciprofloxacin-resistant microor-
ganism was isolated (supplementary Appendix 7,
https://www.jurology.com).
In 73 of the 132 patients with infectious compli-
cations within 7 days after PB (55%), blood cultures
were taken (unknown: 5 patients). In 27 of these 73
blood samples (37%) E. coli was cultured, of which
78% were ciprofloxacin-resistant. Bacteremia was
found in 1.0% of the TRUSPB cohort and 0.3% of
TRMRIPB cohort. No patients with bacteremia
were found in other cohorts (Table 3).
DISCUSSION
In this retrospective study, we compared infectious
complication rates after different types of PB with
various biopsy core numbers. We found that trans-
perineal PB (TPFUSPB) significantly reduced the risk
of infectious complications. Reducing the number of
biopsy cores by transrectal targeted PB only
(TRFUSPB and TRMRIPB) also resulted in a lower
risk of infectious complications compared to TRUSPB.
Our results differ from those of a solid meta-
analysis including 11 randomized controlled trials
that primarily compared the diagnostic accuracy of
standard versus extended number of biopsy cores
and showed no effect of biopsy core number on in-
fectious complications after PB.11 In our study,
however, we primarily focused on the infectious
complications after standard (TRUSPB) and
reduced number of biopsy cores (TRFUSPB and
TRMRIPB), which explains the conflicting results.
Our results are supported by a comparative series of
45 patients who underwent both TRMRIPB and
TRUSPB showing less fever after TRMRIPB
compared to TRUSPB (2.2% versus 4.4%).13 More-
over, a post hoc analysis of a randomized controlled
 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES
Table 3. Main findings
Transrectal Ultrasound-Guided
PB
Targeted Biopsies 10
Biopsy Cores
% Infectious complications within 7 4.0 (104)
days post-biopsy (No.), adjusted OR
(95% CI)
% Infectious complications within 30 4.8 (125)
days post-biopsy (No.), adjusted OR
(95% CI)
% Hospitalization within 7 days post- 2.8 (73)
biopsy (No.)
% Bacteremia within 7 days post-biopsy 1.0 (25)
(No.)
TRUS, transrectal ultrasound.
trial comparing the diagnostic accuracy of 3 MRI-
based targeted PB techniques showed lower infec-
tion rates after TRMRIPB (urinary tract infection
[UTI] 2.6%; fever 1.3%; 77) and TPFUSPB (UTI
1.3%; fever 2.5%; 79) than after TRUSPB (UTI 6.4%;
fever 5.1%; 78).17
In our study, after systematic TRUSPB infection
rates were 4.0% and 4.8% within 7 and 30 days,
respectively. These rates are lower than those in the
aforementioned meta-analysis reporting infections
in 5.6% of all patients (657) after TRUSPB with
comparable biopsy core number.11 This difference
could be explained by the retrospective nature of our
study, using data that were originally collected for
other purposes: as a result no active patient fol-
lowup specifically regarding infectious complica-
tions was performed.
A remarkable result of our study is the higher
infection rate after TRMRIPB (2.1%) compared to
TRFUSPB (1.0%). This difference might be
explained by the longer procedural and inoculation
time in TRMRIPB. No other studies have been
published on this subject.
While the European guidelines prior to 2019
state to perform combined systematic and targeted
biopsy only in patients with positive mpMRI un-
dergoing repeat PB, current guidelines advise to
perform combined systematic and targeted biopsy in
biopsy na€ıve patients with positive mpMRI as
well.26 Since our study was performed between 2012
and 2019, in our TRUSPB cohort a relatively small
proportion consists of combined systematic and
targeted biopsies (8.3%; 2,607). Because of the
higher number of biopsy cores when combining
systematic with targeted PB, it cannot be excluded
that currently the percentage of infectious compli-
cations is even higher than found in our study,
although this was not found in studies comparing 6-
to 12-core versus 18- to 24-core transrectal PB.20e22
To investigate the effect of biopsy core number on
the risk of infection we used cutoff points for biopsy
core number in our study (4 or 10 depending on the
115
Transrectal Targeted MRI-TRUS Transrectal Targeted In-Bore Transperineal MRI-TRUS
Fusion or TRUSPB 4 Biopsy MRI-Guided PB 4 Biopsy Fusion Guided PB 10 Biopsy
Cores Cores Cores
1.0 (4), 0.41 (0.12e1.12) 2.1 (19), 0.68 (0.37e1.20) 1.3 (4), 0.29 (0.09e0.73)
1.3 (5), 0.42 (0.14e1.04) 2.3 (21), 0.58 (0.33e0.99) 2.6 (8), 0.46 (0.19e0.96)
0.3 (1) 1.2 (11) 0.0 (0)
0.3 (3) 0.0 (0) 0.0 (0)
PB technique). These cutoff points are realistic:
15.9% of all patients who underwent TRUSPB were
excluded based on biopsy core number. In the
TRFUSPB cohort, TRMRIPB cohort and the
TPFUSPB cohort 7.6%, 7.8% and 22% of all patients
were excluded based on biopsy core number,
respectively.
Similar to other studies,8,11,17,24 our study shows
that transperineal PB compares favorably to sys-
tematic TRUSPB concerning the risk of infectious
complications. In fact, some guidelines currently
recommend performing transperineal PB to reduce
the risk of infection.23 Transperineal PB, however,
requires more specific equipment and training.
Recent studies showed that the tolerability of
transperineal PB under local anesthesia was similar
to TRUSPB, which may improve the uptake of
transperineal PB.27 Based on the results of our
study, targeted PB might be a reasonable alterna-
tive as well. It should be noted that hospital A is an
expertise center for the clinical implementation of
mpMRI in diagnosing prostate cancer and focuses
on MRI-based targeted transrectal PB only. Current
guidelines do not advise to perform targeted PB only
in biopsy na€ıve patients. However, given the expe-
rience that is gained with mpMRI, we expect that
targeted PB will be applied more widely in the
future. Off course, diagnostic accuracy should be
decisive here, which was beyond the scope of our
study.
A few remarks must be made. A part of the pa-
tients in the transrectal PB cohorts received local
anesthesia with periprostatic lidocaine injection
(passing the rectal mucosa), while in the trans-
perineal PB cohort all patients received general or
spinal anesthesia. Previous studies have shown no
influence of anesthesia type on post-biopsy in-
fections rates.11 Additionally, it is important to note
that disease severity matters as well. We found rela-
tively low sepsis rates compared to other studies,2 which
could be related to the strict sepsis criteria (qSOFA
[quick Sepsis Related Organ Failure Assessment]) we
116 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES

Figure 2. Categorization of the 4 different cohorts per biopsy year. Infectious complications within 7 days after PB are shown in blue.
TRUS, transrectal ultrasound.

used, making it impossible to reliably compare sepsis hospitalized, which might indicate a milder course of
rates between the different cohorts. In the TPFUSPB infections after transperineal PB.
cohort, remarkably, none of the patients with post- The principal strength of this study is that we
biopsy infections had systemic symptoms or was primarily focused on infectious complication rates

Figure 3. Infectious complications (%) within 7 days after PB. The distribution of the types of infection per cohort are shown. TRUS,
transrectal ultrasound.
 EFFECT OF BIOPSY TECHNIQUE ON INFECTION RATES 117

after PB in a large cohort of patients, directly
comparing different PB techniques with various
numbers of biopsy cores. Since currently data on
this subject is limited, our study makes a significant
contribution on the discussion how to reduce in-
fections after PB.
A limitation of our study is that infection rates
after transperineal biopsy with different number of
cores were not compared. Infection rates in our
transperineal cohort (16
3.7 biopsy cores), howev-
er, were comparable to infection rates reported by
Wegelin et al after transperineal PB (4 biopsy cores)
in a Dutch cohort of patients.17
We have modeled our data using logistic regres-
sion adjusting for confounders that have previously
been consistently shown to be related to our primary
outcome. Diabetes is a well-known risk factor,3,28e30
while the covariates “biopsy year” and “hospital”
account for other factors that are not directly
measurable/observable such as interhospital differ-
ences in ciprofloxacin resistance rates and duration
of prophylaxis. Additionally, in hospital A, each year
more TRFUSPBs were performed while the number
of TRUSPBs decreased over the years. The covari-
ate “ciprofloxacin prophylaxis” was included in our
model to account for differences in the type of
antibiotic prophylaxis. Other demographic variables
did not vary substantially and therefore are not
expected to have an impact on our estimates.
CONCLUSIONS
Infections after PB can be reduced using a trans-
perineal approach. Based on the results of our
study, reducing the number of biopsy cores by
using a transrectal targeted PB only approach
could be a reasonable alternative. In view of the
high percentage of ciprofloxacin-resistant micro-
organism isolated from urine cultures of patients
after PB, culture-based prophylaxis could poten-
tially contribute to the reduction of infectious
complications. A prospective multicenter trial on
culture-based oral prophylaxis in transrectal PB
(PRO-SWAP; NCT03228108) is currently being
performed.
ACKNOWLEDGMENTS
The pathology departments of both hospitals are
gratefully acknowledged for providing us data from
the nationwide network and registry of histo- and
cytopathology.

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