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19 Comparison ofOutcomes withTransperineal Versus Transrectal Image-Targeted Prostate Biopsy
213
biopsy with concomitant systematic biopsy [25].
They found that the TP approach was superior at
detecting csPCa overall (27.5% vs. 19.5%,
P=0.012) and in patients with anterior lesions,
apical lesions, or with large prostates (37.8% vs.
18.3%, P=0.044; 34.6% vs. 14.7%, P=0.002;
and 25% vs. 5.1%, P= 0.033). Rabah and colleagues assessed MRI-US fusion TP (142
patients) versus TR (165 patients) biopsy and
found TP biopsy diagnosed signicantly more
csPCa compared to TR (71% vs. 43.7%,
P=0.002) [26].
One study exclusively looking at highresolution micro-ultrasound-MRI fusion populations showed no signicant difference in the
ability to detect csPCa in TP and TR groups [27].
In this study, the micro-US used was quoted to
have a three times greater resolution compared to
standard TRUS, and all patients with anterior
lesions were placed in the TP group, which may
account for the similar detection rate.
Tu and colleagues performed a systematic
review and meta-analysis comparing TP and TR
approaches in all image-guided populations (cognitive, MRI-US and in-bore). They assessed studies that performed a head-to-head analysis of TP
versus TR results, where the reference standard
was systematic TP biopsy, studies using prostatectomy specimens were not included and the
denition of csPCa was heterogenous. A total of
328 TP and 315 TR-fusion biopsies were included
across four studies, with no subgroup analysis of
various forms of image targeting performed.
They concluded that the TP approach was more
accurate in diagnosing csPCa (62.2% TP vs.
41.3% TR, OR 2.37, 95% CI 1.71–3.26), and
superior in diagnosing anterior tumours [28]. A
subsequent meta-analysis by Loy and colleagues
examined a total of 765 via TR and 1387 via TP
in MRI-US fusion biopsies and arrived at a different conclusion. They found that TP and TR
approaches had comparable sensitivity, and no
signicant difference between the two approaches
when diagnosing csPCa [29]. Although, no subgroup analysis based on tumour location was
undertaken and the pre-biopsy PIRADS scores
were not included. The authors theorised that the
difference in these analysis outcomes could be
explained by different article inclusion parameters. Loy et al. included articles that used
software- based fusion (not cognitive or in-bore
fusion), and also included articles that used either
radical prostatectomy or a 24-core systematic
biopsy as the reference standard.
Studies comparing TR and TP techniques
exclusively in the cognitive fusion or in-bore
populations are scarce; however, a few studies
compared TP and TR inadvertently across different targeting modalities. The FUTURE trial was
a post hoc analysis examining outcomes between
TR in-bore fusion biopsy versus TR cognitive
fusion biopsy versus TP MRI-US fusion biopsy,
in men requiring repeat prostate biopsy, and did
not nd a signicant difference in the detection
of csPCa between groups [30]. A small study
comparing MRI-US fusion TP biopsy (92
patients) with cognitive fusion TR biopsy (85
patients) found that there was a higher detection
rate of csPCa in the MRI-US TP group [31],
although it is worth noting the TP cohort was collected several years after the TR cohort. Claros
et al. compared MRI-guided micro-ultrasound
biopsies (using both MRI cognitive guidance
with TR micro-ultrasound) performed via the TR
approach (47 patients) with robotic MRI-US
fusion via the TP approach (222 patients) and
found the micro-ultrasound cognitive fusion TR
technique had higher detection of csPCa in the
targeted cores (38% vs. 23%, P = 0.02) [32].
Yaxley and colleagues compared in-bore MRIguided biopsy and cognitive fusion TR and TP
biopsies and found no signicant difference in
the ability to detect csPCa [33].
Meta-analysis reveals that image targeting
improves concordance with radical prostatectomy specimens compared to systematic biopsy
alone [34]. In the image-targeted population, a
large retrospective analysis of patients who had
undergone radical prostatectomy following
biopsy, found that the TP approach had an
improved concordance with nal pathology compared to the TR approach (OR 1.7, 95% CI
1.2–2.5, P<0.01) [35].
Although there is a lack of any large prospective trials comparing the TP and TR route in a
single image-guided population, based on low
214
J. McDonald et al.
certainty evidence, it seems that TP may have a
specic diagnostic advantage in populations with
anterior tumours and large prostates, which may
explain the increase csPCa detection overall as
well [28, 36]. In the two studies with balanced
cohorts, there was only a small percentage of
anterior tumours in the analysis (16/200 and
15/150), which doesn’t completely explain this
observation [21, 22], and Tewes etal. found that
the TP approach was superior even when accounting for tumour location [37].
Complications
Infections andSepsis
Prostate biopsy via the TR approach is reported
to have a higher risk of post-procedure sepsis,
bacterial prostatitis, and urinary tract infection
compared with the TP route [7, 13]. The pathophysiological explanation of this relates to the
direct inoculation of rectal bacteria into the prostate via the biopsy needle, as evidenced by studies looking at the difference in bacterial load in
the prostate cores following each biopsy route
[8]. A single ad hoc analysis of a randomised
controlled trial assessing image-targeted biopsy
by Wegelin et al., suggests lower complications
with the TP approach, even when corrected for
number of cores [30]. They found that rates of
urinary tract infection were lowest in groups targeted via MRI in-bore TR biopsy, compared with
MRI-US fusion TP and nally cognitive fusion
TR biopsy (52.6% in MRI in-bore, 70.9% in
FUS-TB, and 84.7% in COG-TB, P<0.001). A
systematic biopsy was not performed in the MRI
in-bore TR cohort but was performed for the
other two arms of the study. When corrected for
the number of cores, TP MRI-US fusion biopsy
had fewer complications than cognitive fusion
TR biopsy (OR 2.56 [95% CI 1.14–5.56,
P<0.05]). Total number of cores was also signicantly associated with minor complications as
described above (OR 1.11 [95% CI 1.06–1.17,
P=0.001]). Rabah etal. found that there was no
difference in rates of UTI between TP and TR
approaches [26], whereas El-Achkar et al. and
Marra etal. showed that TP biopsies had a lower
rate of post-procedure UTI [38, 39].
Urinary Retention
One study of 177 patients suggested that TP
MRI-US fusion biopsies have a higher rate of
post-procedure urinary retention compared to
cognitive fusion biopsy via the TR approach
(18.5% vs. 4.7%, P = 0.009); however, signicantly more cores were taken in the TP group (26
vs. 20, P=0.001) [31]. Rabah etal. found there
was no difference in the rates of urinary retention
between TP and TR approaches. Despite any
small differences, it is consistently demonstrated
that rates of urinary retention are low across large
prospective series in TP cohorts, consistently
reported below 2% [40–42].
Bleeding
Minimal data compares bleeding rates (haematuria, rectal bleeding, haematospermia) between
the two approaches in a targeted biopsy population. Wegelin etal. describe lower rates of rectal
bleeding and haematuria following in-bore MRItargeted biopsy via the TR route compared with
TP MRI-US biopsy and cognitive fusion TR
biopsy [30]. The results are limited by the fact
that the TR in-bore MRI group did not have concurrent systematic biopsy, whereas the other
groups did. Increasing the number of cores
increased the overall risk of any adverse effect.
They found that the biopsy did not impact urinary
symptoms (based on IPSS) or erective function
(IIEF scores). Large cohorts of exclusive TP
biopsy have also demonstrated that TP biopsy
has no impact on IPSS and erectile function, with
only minor rates of bleeding [17, 41].
Cost-Eectiveness andAccess
Accessibility and cost can inuence the overall
uptake of a technical approach. For any procedure, local resourcing needs to be considered in
19 Comparison ofOutcomes withTransperineal Versus Transrectal Image-Targeted Prostate Biopsy
215
balance with the diagnostic and complication
prole. Performing prostate biopsies via the TR
approach has been widely accepted as historically being the most cost-efcient option due to
the outpatient setting, reducing costs and equipment compared with TP biopsies previously
requiring a disposable template grid [43].
Targeted biopsy via the TP route under LA is an
emerging area with promising results, with the
obvious benet of avoiding the cost and requirements for hospital operating theatres and
anaesthetists.
The feasibility of TP biopsy under LA has
been demonstrated in studies looking specically
at image-targeted biopsy [44], as well as more
broadly [40]. TP under LA was found to be a feasible technique from both cancer detection and
complication perspectives. While some use disposable devices to guide the needle direction, the
technique can also be performed free hand, thus
not requiring increased resources compared with
the TR approach. From a patient tolerability perspective, a prospective study looking at 128
patients (TR 61 and TP 67) undergoing systematic and targeted biopsy under local anaesthetic
found that patients had similar pain and IPSS
scores during TP and TR image-targeted procedures. The main difference found was that the
pain associated with the administration of LA in
the TP group was signicantly higher [15].
An Australian cost analysis and review of
2048 targeted and systematic prostate biopsies at
a single centre found that, although the routine
costs of TP biopsy were higher than TR (AU$4413
vs. AU$3220), when the two approaches were
compared incorporating the cost of complications and subsequent treatment, they became
equivalent (AU$6764 vs. AU$6360, P = 0.98)
[45]. They found a higher rate of re-presentation
and readmissions due to infection post-TR biopsy
(TR 43/49, 93.4%; TP 14/24, 58.3%; P=0.007).
The authors’ conclusion, once all factors were
considered, was that the implementation of the
TP approach resulted in a reduction in cost,
although it is worth noting that this nding may
have been confounded by the concurrent imple-
mentation of a mpMRI-based triage system. In
regard to operative time, Rabah etal. found that
the time taken for the TP approach was 41min
versus 13min for the TR approach in their study
of 307 patients [26].
The learning curve is an important consideration when considering procedure cost and
access. A recent large study of over 1000 patients
by Calleris and colleagues demonstrates that
US-MR fusion TP biopsy under local anaesthesia
has a relatively short learning curve for procedure duration, even in operators naive to the
fusion approach [16]. Regardless, it is demonstrated that targeted biopsy is safe and effective
throughout the learning curve for either approach
[16, 46]. We know that operator expertise is also
signicantly associated with higher detection
rates of csPCa and is an independent predictor of
csPCa detection (OR1.9, P= 0.004) [47]. There
is minimal data directly comparing the learning
curve of TR versus TP-targeted biopsy and any
difference in costs related to retraining specic to
the different approaches.
Conclusion
Although the level of evidence is low, there may
be advantages in both the diagnostic accuracy of
csPCa and the rates of infection with the TP
approach. The TP approach may improve sampling for anterior and apical tumours. While the
non-infectious complication prole appears
similar for the two approaches, based on retrospective evidence, advantages in terms of infections seemed important in favour of TP, with
some international guidelines recommending
the TP route. However, other guidelines panels
are yet to do so [4, 5]. Randomised control trials
are underway, which may soon provide a high
level of evidence to support or not the possible
advantages of the TP route seen in retrospective
cohort studies [48, 49] (NCT03650153,
NCT03366792, NCT03044197). Further information about these upcoming trials can be seen
in Table19.1.
216
Table 19.1 Emerging randomized control trials with either preliminary publications or early data available
Trial Population Outcomes
PERFECT [48]
– Multicentre
randomised control
trial
– Results pending
PREVENT [49]
– Multicentre
randomised
controlled trial
– Results published
in 2024
Comparing fusion MRI-US fusion
targeted biopsy’s via transperineal
vs. transrectal route
Comparing infectious complications
between MRI-targeted transperineal
biopsies without antibiotics
prophylaxis and MRI-targeted
transrectal biopsies with targeted
antibiotic prophylaxis
Detection of clinically signicant prostate
cancer (ISUP grade 2 and above)
Clinical safety regarding infection, readmission
to hospital and pain
Urinary and sexual QoL scores
Results pending publication
Detection of clinically signicant cancer and
infectious complications
Results
There was an absence of infectious
complications in the image-targeted
transperineal biopsy group (0%) and did not
compromise cancer detection
J. McDonald et al.
References
1. Prostate cancer in Australia statistics 2022.
https://www.canceraustralia.gov.au/cancer- types/
prostate- cancer/statistics.
2. Schoots IG, Roobol MJ, Nieboer D, Bangma CH,
Steyerberg EW, Hunink MGM. Magnetic resonance
imaging–targeted biopsy may enhance the diagnostic accuracy of signicant prostate cancer detection
compared to standard transrectal ultrasound-guided
biopsy: a systematic review and meta-analysis. Eur
Urol. 2015;68(3):438–50. www.Perineologic.com/
precisionpoint/.
3. Wegelin O, van Melick HHE, Hooft L, Bosch J,
Reitsma HB, Barentsz JO, et al. Comparing three
different techniques for magnetic resonance imagingtargeted prostate biopsies: a systematic review of inbore versus magnetic resonance imaging-transrectal
ultrasound fusion versus cognitive registration. Is there
a preferred technique? Eur Urol. 2017;71(4):517–31.
4. Wei JT, Barocas D, Carlsson S, Coakley F, Eggener
S, Etzioni R, etal. Early detection of prostate cancer:
AUA/SUO guideline part I: prostate cancer screening.
J Urol. 2023;210(1):46–53.
5. Edn presented at the EAU Annual Congress Milan
2023 ISBN 978-94-92671-19-6. EAU Guidelines.
6. Roberts MJ, Williamson DA, Hadway P, Doi SAR,
Gardiner RA, Paterson DL. Baseline prevalence of
antimicrobial resistance and subsequent infection
following prostate biopsy using empirical or altered
prophylaxis: a bias-adjusted meta-analysis. Int J
Antimicrob Agents. 2014;43(4):301–9.
7. Anderson E, Leahy O, Cheng AC, Grummet J.Risk
factors for infection following prostate biopsy—a
case control study. BMC Infect Dis. 2015;15:580.
8. Werneburg GT, Adler A, Zhang A, Mukherjee SD,
Haywood S, Miller AW, etal. Transperineal prostate
biopsy is associated with lower tissue core pathogen
burden relative to transrectal biopsy: mechanistic
underpinnings for lower infection risk in the transperineal approach. Urology. 2022;165:1–8.
9. Chung HS, Hwang EC, Yu HS, Jung SI, Lee SJ,
Lim DH, et al. Prevalence of uoroquinolone-resistant rectal ora in patients undergoing transrectal
ultrasound- guided prostate needle biopsy: a prospective multicenter study. Int J Urol. 2018;25(3):278–83.
10. Perineologic, Inventor Precision Point Transperineal
Access System. Perineologic.com/precisionpoint/
11. Pepdjonovic L, Tan GH, Huang S, Mann S,
Frydenberg M, Moon D, etal. Zero hospital admissions for infection after 577 transperineal prostate
biopsies using single-dose cephazolin prophylaxis.
World J Urol. 2017;35(8):1199–203.
12. Basourakos SP, Alshak MN, Lewicki PJ, Cheng E,
Tzeng M, DeRosa AP, et al. Role of prophylactic
antibiotics in transperineal prostate biopsy: a systematic review and meta-analysis. Eur Urol Open Sci.
2022;37:53–63.
13. Grummet J. How to biopsy: transperineal versus
transrectal, saturation versus targeted. What’s the evidence? Urol Clin N Am. 2017;44(4):525–34.
14. Schouten MG, van der Leest M, Pokorny M,
Hoogenboom M, Barentsz JO, Thompson LC, etal.
Why and where do we miss signicant prostate cancer with multi-parametric magnetic resonance imaging followed by magnetic resonance-guided and
Transrectal ultrasound-guided biopsy in biopsy-naïve
men? Eur Urol. 2017;71(6):896–903.
15. Berquin C, Perletti G, Develtere D, Van Puyvelde
H, Pauwels E, De Groote R, etal. Transperineal vs.
transrectal prostate biopsies under local anesthesia:
a prospective cohort study on patient tolerability and
complication rates. Urol Oncol. 2023;41:388.e17.
16. Calleris G, Marquis A, Zhuang J, Beltrami M, Zhao
X, Kan Y, etal. Impact of operator expertise on transperineal free-hand mpMRI-fusion-targeted biopsies
under local anaesthesia for prostate cancer diagnosis: a multicenter prospective learning curve. World J
Urol. 2023;41:3867.
17. Marra G, Zhuang J, Beltrami M, Calleris G, Zhao
X, Marquis A, et al. Transperineal freehand multiparametric MRI fusion targeted biopsies under local
anaesthesia for prostate cancer diagnosis: a mul-
19 Comparison ofOutcomes withTransperineal Versus Transrectal Image-Targeted Prostate Biopsy
217
ticentre prospective study of 1014 cases. BJU Int.
2021;127(1):122–30.
18. Lu M, Luo Y, Wang Y, Yu J, Zheng H, Yang
Z. Transrectal versus transperineal prostate biopsy
in detection of prostate cancer: a retrospective study
based on 452 patients. BMC Urol. 2023;23(1):11.
19. Zhou C, Tang Y, Deng Z, Yang J, Zhou M, Wang L,
et al. Comparison of (68)Ga-PSMA PET/CT and
multiparametric MRI for the detection of low- and
intermediate-risk prostate cancer. EJNMMI Res.
2022;12(1):10.
20. Ferraro DA, Becker AS, Kranzbühler B, Mebert I,
Baltensperger A, Zeimpekis KG, et al. Diagnostic
performance of (68)Ga-PSMA-11 PET/MRI-guided
biopsy in patients with suspected prostate cancer: a
prospective single-center study. Eur J Nucl Med Mol
Imaging. 2021;48(10):3315–24.
21. Pepe P, Garu A, Priolo GD, Pennisi
M. Multiparametric MRI/TRUS fusion prostate
biopsy: advantages of a transperineal approach.
Anticancer Res. 2017;37(6):3291–4.
22. Pepe P, Garu A, Priolo G, Pennisi M.Transperineal
versus transrectal MRI/TRUS fusion targeted biopsy:
detection rate of clinically signicant prostate cancer.
Clin Genitourin Cancer. 2017;15(1):e33–e6.
23. Ber Y, Segal N, Tamir S, Benjaminov O, Yakimov M,
Sela S, et al. A noninferiority within-person study
comparing the accuracy of transperineal to transrectal
MRI-US fusion biopsy for prostate-cancer detection.
Prostate Cancer Prostatic Dis. 2020;23(3):449–56.
24. Zattoni F, Marra G, Kasivisvanathan V, Grummet J,
Nandurkar R, Ploussard G, et al. The detection of
prostate cancer with magnetic resonance imagingtargeted prostate biopsies is superior with the transperineal vs the transrectal approach. A European
Association of Urology-young academic urologists
prostate cancer working group multi-institutional
study. J Urol. 2022;208(4):830–7.
25. Koparal MY, Sözen TS, Karşıyakalı N, Aslan G,
Akdoğan B, Şahin B, et al. Comparison of transperineal and transrectal targeted prostate biopsy
using Mahalanobis distance matching within propensity score caliper method: a multicenter study
of Turkish Urooncology Association. Prostate.
2022;82(4):425–32.
26. Rabah D, Al-Taweel W, Khan F, Arafa M, Mehmood
S, Mokhtar A, et al. Transperineal versus transrectal multi-parametric magnetic resonance imaging fusion targeted prostate biopsy. Saudi Med J.
2021;42(6):649–54.
27. Rakauskas A, Peters M, Martel P, van Rossum PSN,
La Rosa S, Meuwly JY, et al. Do cancer detection
rates differ between transperineal and transrectal
micro-ultrasound mpMRI-fusion-targeted prostate
biopsies? A propensity score-matched study. PLoS
One. 2023;18(1):e0280262.
28. Tu X, Liu Z, Chang T, Qiu S, Xu H, Bao Y, et al.
Transperineal magnetic resonance imaging-targeted
biopsy may perform better than transrectal route in
the detection of clinically signicant prostate cancer:
systematic review and meta-analysis. Clin Genitourin
Cancer. 2019;17(5):e860–e70.
29. 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):650–60.
30. Wegelin O, Exterkate L, van der Leest M, Kelder
JC, Bosch J, Barentsz JO, et al. Complications and
adverse events of three magnetic resonance imagingbased target biopsy techniques in the diagnosis of
prostate cancer among men with prior negative
biopsies: results from the FUTURE trial, a multicentre randomised controlled trial. Eur Urol Oncol.
2019;2(6):617–24.
31. Hsieh PF, Chang TY, Lin WC, Chang H, Chang CH,
Huang CP, et al. A comparative study of transperineal software-assisted magnetic resonance/ultrasound
fusion biopsy and transrectal cognitive fusion biopsy
of the prostate. BMC Urol. 2022;22(1):72.
32. Claros OR, Tourinho-Barbosa RR, Fregeville A,
Gallardo AC, Muttin F, Carneiro A, etal. Comparison
of initial experience with transrectal magnetic resonance imaging cognitive guided micro-ultrasound
biopsies versus established transperineal robotic
ultrasound magnetic resonance imaging fusion biopsies for prostate cancer. J Urol. 2020;203(5):918–25.
33. Yaxley AJ, Yaxley JW, Thangasamy IA, Ballard
E, Pokorny MR. Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided
prostate biopsies for prostate imaging-reporting and
data system (PI-RADS) 3-5 MRI lesions. BJU Int.
2017;120(Suppl 3):43–50.
34. Goel S, Shoag JE, Gross MD, Al Awamlh BH,
Robinson B, Khani F, et al. Concordance between
biopsy and radical prostatectomy pathology in the
era of targeted biopsy: a systematic review and metaanalysis. Eur Urol Oncol. 2020;3(1):10–20.
35. Zattoni F, Marra G, Martini A, Kasivisvanathan V,
Grummet J, Harkin T, et al. Is there an impact of
transperineal versus transrectal magnetic resonance
imaging-targeted biopsy on the risk of upgrading in
nal pathology in prostate cancer patients undergoing radical prostatectomy? An European Association
of Urology-young academic urologists prostate cancer working group multi-institutional study. Eur Urol
Focus. 2023;9(4):621–8.
36. Rai BP, Mayerhofer C, Somani BK, Kallidonis P,
Nagele U, Tokas T. Magnetic resonance imaging/
ultrasound fusion-guided transperineal versus magnetic resonance imaging/ultrasound fusion-guided
transrectal prostate biopsy—a systematic review. Eur
Urol Oncol. 2021;4(6):904–13.
37. Tewes S, Peters I, Tiemeyer A, Peperhove M,
Hartung D, Pertschy S, et al. Evaluation of MRI/
ultrasound fusion-guided prostate biopsy using transrectal and transperineal approaches. Biomed Res Int.
2017;2017:2176471.
218
J. McDonald et al.
38. El-Achkar A, Abou Heidar N, Labban M,
Al-Moussawy M, Moukaddem H, Nasr R, etal. MRI/
US fusion transperineal versus transrectral biopsy of
prostate cancer: outcomes and complication rates, a
tertiary medical center experience in the Middle East.
Turk J Urol. 2022;48(2):98–105.
39. Marra G, Ploussard G, Futterer J, Valerio
M. Controversies in MR targeted biopsy: alone or
combined, cognitive versus software-based fusion,
transrectal versus transperineal approach? World J
Urol. 2019;37(2):277–87.
40. Stefanova V, Buckley R, Flax S, Spevack L, Hajek D,
Tunis A, etal. Transperineal prostate biopsies using
local anesthesia: experience with 1,287 patients.
Prostate cancer detection rate, complications and
patient tolerability. J Urol. 2019;201(6):1121–6.
41. Marra G, Zhuang J, Marquis A, Zhao X, Calleris G,
Kan Y, et al. Pain in men undergoing Transperineal
free-hand multiparametric magnetic resonance imaging fusion targeted biopsies under local anesthesia:
outcomes and predictors from a multicenter study of
1,008 patients. J Urol. 2020;204(6):1209–15.
42. Lopez JF, Campbell A, Omer A, Stroman L, Bondad
J, Austin T, 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):311–8.
43. Thomson A, Li M, Grummet J, Sengupta
S. Transperineal prostate biopsy: a review of technique. Transl Androl Urol. 2020;9(6):3009–17.
44. Kozel Z, Martin C, Mikhail D, Smith A, Grifths
L, Nethala D, et al. Initial experience and cancer
detection rates of ofce-based transperineal mag-
netic resonance imaging-ultrasound fusion prostate
biopsy under local anesthesia. Can Urol Assoc J.
2022;16(7):E350–e6.
45. Roberts MJ, Macdonald A, Ranasinghe S, Bennett H,
Teloken PE, Harris P, etal. Transrectal versus transperineal prostate biopsy under intravenous anaesthesia: a clinical, microbiological and cost analysis
of 2048 cases over 11 years at a tertiary institution.
Prostate Cancer Prostatic Dis. 2021;24(1):169–76.
46. Checcucci E, Piramide F, Amparore D, De Cillis S,
Granato S, Sica M, etal. Beyond the learning curve of
prostate MRI/TRUS target fusion biopsy after more
than 1000 procedures. Urology. 2021;155:39–45.
47. Stabile A, Dell'Oglio P, Gandaglia G, Fossati N,
Brembilla G, Cristel G, etal. Not all multiparametric magnetic resonance imaging-targeted biopsies are
equal: the impact of the type of approach and operator expertise on the detection of clinically signicant
prostate cancer. Eur Urol Oncol. 2018;1(2):120–8.
48. Touzani A, Fiard G, Barret E, Renard-Penna R,
Salin A, Pradère B, etal. Clinical trial protocol for
PERFECT: a randomised controlled trial comparing the efciency and tolerance of transperineal
fusion versus transrectal imaging-targeted prostate
biopsies (CCAFU-PR1 study). Eur Urol Open Sci.
2022;45:76–80.
49. Hu JC, Assel M, Allaf ME, Ehdaie B, Vickers AJ,
Cohen AJ, et al. Transperineal versus transrectal
magnetic resonance imaging–targeted and systematic prostate biopsy to prevent infectious complications: the PREVENT randomized trial. Eur Urol.
2024;86:61.
Using Multicore, Transperineal
Prostate Mapping Biopsy
toDetect, Localize, andTreat
thempMRI Invisible Lesion
E.DavidCrawford, FranciscoG.La Rosa,
PaulB.Arangua, andPriyaN.Werahera
20
Introduction
Prostate Cancer PCa is the second most common solid tumor in men worldwide and ranks as
the fth cause of cancer-related mortality [1]. An
estimated 288,300 men in the United States will
be diagnosed with this disease in 2023, and
34,700 are expected to die [2]. The current standard of care recommends prostate biopsies when
a patient has prostate-specic antigen levels
(PSA)≥4ng/mL or has an abnormal digital rectal exam (DRE), except both these screening tests
lack specicity for cancer. The use of PSA cutoff
1.5, however, has shown maximum sensitivity
and specicity for PCa risk assessment with a
0.87 area under the curve [3]. TRUS-guided prostate biopsies are subjected to serious sampling
errors, leading to the detection of indolent cancer
E. D. Crawford
University of San Diego, Koman Family Outpatient
Pavilion, La Jolla, CA, USA
e-mail: edc@edavidcrawford.com
F. G. La Rosa · P. N. Werahera (*)
Department of Pathology, University of Colorado
Anschutz Medical Campus, Aurora, CO, USA
e-mail: Francisco.LaRosa@CUAnschutz.Edu;
Priya.Werahera@CUAnschutz.Edu
P. B. Arangua
Department of Urologic Oncology, University of
Colorado Anschutz Medical Campus,
Aurora, CO, USA
e-mail: Paul.Arangua@CUAnschutz.Edu
while missing csPCa [4, 5]. PSA/DRE-based
screening for PCa may saves lives, but it remains
controversial due to increased harm from overdiagnosis and complications of treatment of indolent disease [6]. Nevertheless, the current clinical
challenge of accurate diagnosis of csPCa still
remains, which warrants denitive treatment
while sparing those with indolent disease.
Clinically Signicant PCa csPCa can be
dened as a lesion with a volume≥ 0.5 cc or
with histopathological grade of Gleason patterns 4 or 5 [5, 7]. Clinical evidence shows poor
outcomes for patients harboring such lesions [8,
9]. Based on the revised classication of
Gleason Grade Groups (GG), csPCa can be categorized into GG2 or higher [10]. mpMRI is
currently the most promising imaging modality
to identify regions within the prostate with
csPCa, including intermediate to high-grade
lesions and thereby direct prostate biopsies to
suspected lesions aiding histopathological diagnosis of this disease. MRI lesions designated
with a Prostate Imaging Reporting and Data
System (PIRADS v2) scores of 3–5 are considered csPCa [11]. A meta- analysis of 12 studies
reported sensitivity of 44% to 87% for detection
of csPCa with PIRADS scores ≥3 in biopsynaive males and men with prior negative biopsies and NPV of 63% to 98% for exclusion of
signicant disease [12].
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
T. J. Polascik et al. (eds.), Imaging and Focal Therapy of Early Prostate Cancer,
https://doi.org/10.1007/978-3-031-66754-1_20
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E. D. Crawford et al.
MRI Lesions Targeted Biopsy The adoption of
MRTB rose rapidly in the US from 0.2% in 2009
to 6.5% in 2015 (p<0.001), mostly concentrated
in urban areas [13]. Many studies have shown
that MRTB detected a higher percentage of
csPCa as opposed to systematic biopsies in men
with elevated PSA or abnormal DRE [14–17]. A
meta-analysis found MRTB detected signicantly more men with csPCa (p < 0.0001) and
signicantly less men with non-csPCa
(p < 0.0001) than systematic TRUS biopsy
(STRB) [14]. The diagnostic yield or the proportion of cores positive for cancer was likewise
greater for MRTB than STRB, with a detection
ratio of 1.16 (95%CI: 1.09–1.24) (p < 0.0001).
Studies have also shown clinicians can spare
prostate biopsies for men without any identiable
lesions on mpMRI, thus preventing infections,
potential overdiagnosis of non-csPCa, and other
urinary complications [16, 17].
NPV of mpMRI While MRTB may have a
superior cancer detection rate among men with
prior negative systematic biopsies in the US [13],
clinicians are, however, facing a dilemma regarding the accuracy of mpMRI when there are no
identiable suspicious lesions, in particular
among biopsy-naïve patients. In a prospective
trial, 1042 men had MR fusion-image-guided
12-core systematic biopsies and csPCa were
diagnosed in 35/217 (16%) of men with no suspicious mpMRI targets [18]. Co-registration of
mpMRI lesions with whole-mount pathology of
prostatectomy specimens showed mpMRI
detected less than half of all PCa foci and less
than two-thirds of csPCa foci [19]. Among csPCa
that remained undetected by mpMRI, 74% were
solitary and 31% were multifocal tumors. The
combined NPV estimates of 48 studies decreased
from 88% to 67% in patients with PIRADS score
≥3 lesions when the overall PCa prevalence
increased from 30% to 60% [20]. These studies
prove that the NPV of mpMRI, which depends on
disease prevalence, may be less than 90% and not
adequate to safely rule out the incidence of
csPCa. Hence, a negative prebiopsy mpMRI is
not a precursor for clinicians to spare systematic
prostate biopsies for biopsy-naïve patients.
TPMB Some csPCa lesions may remain invisi-
ble to mpMRI due to their anatomical locations
and may also remain undetected by systematic
biopsies. In a cohort of 223 biopsy-naïve patients,
csPCa missed by MRTB were located dorsolateral (58%) and apical (37%), whereas those
missed by STRB were located anteriorly (79%),
anterior mid-prostate (50%), and anterior apex
(23%) [21]. Since the disease is largely multifocal, it is important to determine the accurate histopathologic grade by sampling the highest
Gleason pattern and pathologic stage of the disease for optimal therapeutic decisions. TPMB is
currently the most accurate biopsy procedure
available to diagnose this disease. Computer simulations of TPMB with 5mm grid interval sampling have established a benchmark of 95%
sensitivity for the diagnosis of csPCa and 95%
NPV for ruling out csPCa in the sampled segment [22]. For comparisons, sextant and laterally
directed biopsy protocols had sensitivities of
56% and 74%, respectively, and NPVs of 71%
and 88%, respectively [5, 7]. An optimal sampling of the prostate with a biopsy density (number of cores/prostate gland volume in cc)≥1.5 is
required to diagnose csPCa, including tumors
≥GG2 and GG1 with volume ≥ 0.5 cc [23].
However, reducing the sampling density below
1.5 has a substantial impact on NPV and, thereby,
the ability of TPMB to exclude csPCa [24].
PCa Biomarkers The limitations of PSA noted
above led to the development of novel biomarkers aimed at better informing the risk of GG ≥2
cancer. Some of the commercially available PCa
biomarkers include PCA3, SelectMDx, PHI,
4Kscore, and ExoDx [25]. These noninvasive
biomarker tests utilize serum and urine samples
and offer cost-effective alternatives to separate
men harboring csPCa from benign or indolent
diseases when prebiopsy mpMRI and STRB
results are inconclusive.
PCA3 mRNA is a non-coding RNA, and it is a
prostate-specic gene overexpressed in PCa cells
compared to benign cells [26]. PCA3 has shown
moderate sensitivity and specicity for diagnosis
of PCa in large studies with >450 patients [27].
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
221
SelectMDx test utilizes mRNA levels of the
homeobox C6-gene (HOXC6) and Distal-Less
Homeobox 1-gene (DLX1) derived from postDRE urine samples to determine risk of PCa.
This test can reduce unnecessary prostate biopsies by 40% assuming a negative test in the decision not to biopsy the patient [28].
Prostate Health Index (PHI) test derived from
serum samples can identify patients with PCa
[29]. PHI is calculated using levels of PSA, [−2]
proPSA, and % free PSA in serum. Performing
prostate biopsies only for patients with PHI ≥36
can signicantly reduce unnecessary biopsy procedures when compared to historical control
groups (36% vs. 60%, p < 0.0001) [30]. There
was a signicant difference in the PHI density
(PHID=PHI/prostate gland volume measured by
TRUS) between csPCa versus non-csPCa (0.7 vs.
0.53, p<0.001) [31].
The 4Kscore is also a blood-based test that
combines levels of 4 Kallikrein proteins (total
PSA, free PSA, intact PSA, and human
Kallikrein-2) with important clinical information
(age, DRE, and any previous biopsy status), to
predict GG2 or higher PCa [32]. At 7.5% cutoff,
the 4Kscore test has a sensitivity of 94% for diagnosing ≥GG2 cancer and a NPV of 95% for ruling out such cancer. The higher scores of 4Kscore
were signicantly associated with higher grade
and more aggressive histology [33].
Limited specicity of PSA for csPCa requires
routine screening, which carries substantial risks
for patients, including frequent unnecessary
prostate biopsies, overdiagnosis of indolent cancer, and biopsy-associated morbidity. MRTB
offers higher detection rates for csPCa, but some
are MRI-invisible and may also remain undetected by STRB. PCa biomarkers offer costeffective alternatives but can be subjected to false
negative and false positive results. TPMB has the
highest sensitivity to identify csPCa and the highest NPV to rule out such lesions, but the procedure is expensive. A shared decision-making
approach is needed to diagnose and treat these
patients.
Institutional Examples
Setting
Patient Cohort A subset of patients at the
University of Colorado Hospital (UCH) elected
TPMB after the initial and repeat transrectal
ultrasound-guided prostate biopsies (TRUS)
were either negative or detected a GG1 cancer
with <5% core involvement. Some of these
patients had 5-alpha reductase inhibitors to
reduce the prostate volume prior to TPMB.Serum
and post-DRE urine samples were collected from
patients prior to TRUS biopsy, and postdiagnostic biopsy tissues were used for PSA and
other PCa biomarker testing. Additional biological samples of consented patients were saved in
the Prostate Biorepository at UCH for future use.
mpMRI Protocol Patients had mpMRI following TRUS biopsy and prior to TPMB.A 3.0Tesla
scanner (GE Signa HDxt-Faireld, CT, USA)
was utilized with an endorectal coil (Medrad
Prostate eCoil-Warrendale, PA, USA) and eightchannel pelvis phased array surface coil. The
prostate imaging protocol included large eld-ofview images of the pelvis and the following highresolution images of the prostate: small
eld-of-view (FOV) tri-planar high-resolution
T2-weighted (T2W) imaging, diffusion-weighted
imaging (DWI) with Apparent Diffusion
Coefcient (ADC) maps (b value of 0, 600 and
1000), and dynamic contrast-enhanced (DCE)
imaging [34]. A subspecialty trained radiologist
employed the Prostate Imaging Reporting and
Data System (PIRADS v2) lexicon for the classication of suspicious mpMRI lesions [11, 35].
PCa Biomarker Protocol Serum and post-DRE
urine samples collected from patients were used
to test several biomarkers to identify patients
with csPCa when their mpMRI results were
inconclusive. PCA3 [26] and SelectMDx tests
used rst-catch ~20mL post-DRE urine samples,
and 4Kscore and phi tests used serum samples
222
E. D. Crawford et al.
stored in the Prostate Biorepository. PCA3≥35
identify patients with PCa while reducing the
number of false positives, but signicantly
increase the false negatives [26]. FDA has
approved a PCA3 cutoff of 25 [36]. Any positive
SelectMDx test (>0%) result indicated the presence of PCa and csPCa, while those with negative results can be spared from prostate biopsy
[28]. The 4Kscore ≥7.5% has high sensitivity to
diagnose csPCa while lower scores ruled out
such cancer with high NPV [32]. The PHI ≥36
indicated the presence of PCa [30] whereas phi
density (PHID = PHID/prostate gland volume
measured at TRUS) ≥0.7 indicated of csPCa
[31]. Beckman & Coulter, OPKO, MDx Health,
and Bostwick Laboratories provided test results
for PHI, 4KScore, SelectMDx, and PCA3,
respectively.
TPMB Protocol TPMB is routinely offered to
the patients at UCH who wish to proceed when
their histopathological results of TRUS biopsies
are inadequate, or PCa biomarkers indicate incidence of PCa or high-grade PCa. The urologist
performed TPMB in the OR under general anesthesia. The protocol included systematic transperineal template-guided prostate biopsy using
real-time transrectal ultrasound guidance to sample the entire prostate gland from apex to base at
5-mm increments with between 55 and 108 cores
per patient, depending on the size of the prostate
gland [37]. In addition, a Civco-type stepping
unit collected transverse ultrasound (US) images
of the prostate in 5-mm intervals from apex to
base for 3D reconstruction.
Histopathology Protocol The proximal end of
each TPMB biopsy core is inked with India ink,
which enables correct orientation of the core, and
then placed in a 10% NBF specimen vial labeled
using the grid coordinate position of the template. Biopsy cores are processed using a standard histological protocol to generate 3″×1″
H&E slides from 5-micron tissue sections.
Histotechnicians mounted multiple color-coded
biopsy cores up to three on each H&E slide to
reduce the cost of the procedure. The genitourinary pathologist provided the histopathological
diagnosis for each biopsy core, including the
Gleason sum, separate lengths of each Gleason
pattern of 3, 4, and 5, core involvement, and location of cancer in mm from the inked-end of the
core. Positive biopsy cores were then compiled
onto 3D models (3DTPMB) of each patient’s
prostate gland utilizing proprietary software
ProView (Applied Coherent Technology,
Herndon, Virginia), which combined histopathological data with transverse US images of the
prostate.
Interpretation of Histopathology
Data Urologists utilized the resulting 3DTPMB
models of the prostate gland with PCa tumor foci
in combination with other relevant clinical information to decide therapeutic options tailored to
each individual patient. csPCa is a lesion with
histopathological grade GG ≥ 2 or GG1 with
volume ≥ 0.5 cc. Final GG was determined
either by the cumulative sum of the individual
Gleason patterns found on TPMB cores [38] or
from the nal pathology report for those patients
who opted for radical prostatectomy surgery. In
the absence of GG2 or higher cancer, 3DTPBM
was used to estimate the approximate volume of
the GG1 lesions to determine clinical
signicance.
Results
Study Patients Clinical outcome data for six
patients who had TPMB at the UCH following
inconclusive TRUS biopsy and/or mpMRI ndings are presented here. Table 20.1 summarizes
clinical data, including TRUS biopsy results. All
except patient (Pt) #4 had elevated PSA above the
standard cutoff of 4ng/mL at the time of TRUS
biopsy. PSAD cutoff of 0.15ng/mL/cc is a commonly used threshold for who should proceed to
a prostate biopsy when MRI ndings are negative
[39]. Except for Pt #3, the rest had their PSAD
above this cutoff, indicating the need for systematic prostate biopsy due to the incidence of ≥GG2
cancer. Table 20.2 presents PCa biomarker
results, mpMRI ndings, TPMB results, and
therapeutic options.