Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5209_Библиотеки_им_академика_М_И_Перельмана.pdf
182
M. B. Rothberg
Fig. 17.1 A 69-year-old man with elevated PSA of
6.44ng/dL and multi-parametric MRI showing PIRADS
category 4 lesion in the midline peripheral zone at the
level of mid-gland, extending to apex. Fusion biopsy
revealed Gleason score of 4+5 (grade group 5) disease.
lesions and a majority (between 53 and 82%) of
satellite tumors based on correlation of imaging to
whole-mount nal radical prostatectomy pathology [38, 39].
Diagnostic Utility ofPSMA PET
Imaging
While several landmark studies have established
the clinical utility of mpMRI for intraprostatic
lesion characterization and reported superior
diagnostic accuracies for identifying csPCa with
MRI/US-fusion-targeted prostate biopsy com-
Pylarify-PSMA PET (2months post-biopsy) showed the
posterior midline prostate lesion from base to apex.
Pathology report after radical prostatectomy showed clinically signicant left and right posterior predominant disease from base to apex
pared to conventional TRUS-guided biopsy, nonnegligible rates of clinically signicant,
MR-invisible disease persist [11, 12]. Multiple
investigations have sought to further optimize
csPCa diagnosis with the addition of PSMA PET/
CT imaging to mpMRI. Donato etal. performed
a retrospective comparison identifying patients
who underwent both imaging modalities prior to
radical prostatectomy with whole-mount histopathological specimen as the ground truth and,
when compared to mpMRI, report 68Ga-PSMA
PET/CT improved sensitivities for identifying
the index lesion (93% vs. 90%), identifying the
presence of bilateral tumors (42% vs. 21%), and
17 Staging Imaging forFocal Therapy ofProstate Cancer
183
identifying the presence of multifocal tumors
(34% vs. 19%) [40]. A study by Koseoglu etal.
stratied patients based on index lesion PIRADS
score and, specically for patients with PIRADS
4 lesions, report 68Ga-PSMA PET/CT demonstrated improved diagnostic accuracy for
identication of the index lesion and satellite
lesions compared to mpMRI [39]. Additionally,
for patients suspected of harboring prostate cancer in the setting of a previous negative biopsy,
negative mpMRI, or positive mpMRI with subsequent negative biopsy, Lopci et al. report
68
Ga-PSMA PET/CT-fusion-targeted prostate
biopsy identied csPCa in 27% of cases [41].
To determine the additive diagnostic value of
PSMA PET/CT imaging to mpMRI, Emmett
et al. conducted a prospective, phase II trial
enrolling biopsy- and imaging-naïve men with
suspected prostate cancer based on elevated
serum PSA and/or abnormal digital rectal examination. Following prostate mpMRI and PSMA
PET/CT scan, patients underwent transperineal
targeted biopsy of all visible lesions followed by
a systematic biopsy. Of the patients with csPCa,
81% had either PSMA-positive or MR-visible
(PIRADS 4 or 5) lesions, and the combination of
both imaging modalities resulted in improved
sensitivity (97%, vs. 83% for mpMRI alone) and
NPV (91%, vs. 72% for mpMRI alone) for the
diagnosis of csPCa [42]. Moreover, an SUV
max
threshold of 12 produced both specicity and
PPV of 100% for the detection of csPCa.
Subsequent development of the PRIMARY
score, which assigns a 1 to 5 score based on the
pattern and intensity of intraprostatic PSMA
avidity, shows promising diagnostic accuracy for
csPCa, but likely requires further validation prior
to mainstream adaption [43].
PSMA-targeted PET/MRI seeks to further
improve upon the diagnostic accuracies associated with each individual imaging modality and
combine information from PSMA-based molecular imaging with enhanced intraprostatic lesion
characterization afforded from various anatomic
and functional sequences of mpMRI. Eiber etal.
performed individual mpMRI, individual PET,
and 68Ga-PSMA HBED-CC PET/MRI on patients
prior to undergoing radical prostatectomy and
reported that, on an individual lesion level, PET/
MRI had a higher sensitivity (76% vs. 64% for
PET and 58% for mpMRI) and specicity (97%
vs. 94% for PET and 82% for mpMRI), as well as
a favorable AUC (0.88 vs. 0.83 for PET and 0.73
for mpMRI) for cancer localization [44].
Additionally, Grubmuller etal. compared [68Ga]
Ga-PSMA-11 PET/MRI to whole-mount radical
prostatectomy specimens and report an overall
PET/MRI tumor staging accuracy of 82.5% (95%
condence interval 73–90) [45]. Overall, initial
investigations studying this novel imaging
modality report favorable diagnostic accuracies
with the future potential to further optimize localized staging of prostate cancer. Additional studies
are warranted to dene the clinical utility of this
technology for diagnostic and potentially therapeutic purposes.
Predictive Value ofPSMA Ligand
Uptake
Increasing values of intraprostatic PSMA ligand
uptake, an indication of relatively increased cellular density and surface PSMA expression, has
demonstrated clinical utility through improved
localized staging of prostate cancer and has also
been shown to be predictive of several clinically
meaningful outcomes. Multiple investigations
have reported the intensity of PSMA ligand
uptake to be directly related to serum PSA levels
[39, 46] and predictive of histopathological
grade. A study by Scheltema etal. reported that
PSMA PET/CT imaging is capable of distinguishing between ISUP grade 1 and ISUP
grade ≥ 2 disease with an SUV
3.95, yielding a sensitivity of 94% and a specicity of 100% for predicting the presence of intermediate- and high-risk disease [47]. Bahler etal.
also report signicantly higher PSMA ligand
uptake for grade group 3 to 5 lesions compared to
grade group 2 lesions (SUV
likewise, Uprimny et al. report a signicantly
higher SUV
(median SUV
for tumors with Gleason score>7
max
21.2) versus those with Gleason
max
score ≤ 7 [46]. In addition to predicting histopathological grade, increasing PSMA ligand
threshold of
max
7.9 vs. 5.3) [38];
max
184
M. B. Rothberg
uptake has also been shown to be predictive of
upgrading events and the presence of adverse
pathologic features, such as locally advanced
tumor stage and positive surgical margins, on
radical prostatectomy pathology [48].
Specically, a systematic review and
meta- analysis of 12 studies including 615 patients
by Woo etal. report PSMA PET/CT imaging is
highly specic (0.87 and 0.94 for ECE and SVI,
respectively), however, only modestly sensitive
(0.72 and 0.68 for ECE and SVI, respectively),
for identifying locally advanced tumor characteristics [49]. Beyond prediction of tumor grade and
localized staging of prostate cancer, increasing
intraprostatic PSMA ligand uptake is also associated with concomitant lymph node positivity
and/or presence of distant metastases [50], as
well as worse biochemical recurrence (BCR)free survival following radical prostatectomy
[51, 52]. Taken together, intraprostatic PSMA
PET/CT imaging may potentially provide added
predictive value to contemporary imaging modalities for localized staging of prostate cancer to
further risk stratify patients and identify those
who are optimal candidates for focal therapeutic
approaches.
References
1. Ahmed HU, et al. Diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer
(PROMIS): a paired validating conrmatory study.
Lancet. 2017;389(10071):815–22.
2. Kasivisvanathan V, et al. MRI-targeted or standard
biopsy for prostate-cancer diagnosis. N Engl J Med.
2018;378(19):1767–77.
3. Rouvière O, etal. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in
biopsy-naive patients (MRI-FIRST): a prospective,
multicentre, paired diagnostic study. Lancet Oncol.
2019;20(1):100–9.
4. Siddiqui MM, et al. Comparison of MR/ultrasound fusion–guided biopsy with ultrasound-guided
biopsy for the diagnosis of prostate cancer. JAMA.
2015;313(4):390–7.
5. Liu W, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat
Med. 2009;15(5):559–65.
6. Ahmed HU.The index lesion and the origin of prostate cancer. N Engl J Med. 2009;361(17):1704–6.
7. Radtke JP, etal. Multiparametric magnetic resonance
imaging (MRI) and MRI–transrectal ultrasound
fusion biopsy for index tumor detection: correlation with radical prostatectomy specimen. Eur Urol.
2016;70(5):846–53.
8. Russo F, et al. Detection of prostate cancer index
lesions with multiparametric magnetic resonance
imaging (mp-MRI) using whole-mount histological sections as the reference standard. BJU Int.
2016;118(1):84–94.
9. Goto Y, etal. Distinguishing clinically important from
unimportant prostate cancers before treatment: value
of systematic biopsies. J Urol. 1996;156(3):1059–63.
10. Rukstalis DB, etal. Prostate cryoablation: a scientic
rationale for future modications. Urology. 2002;60(2
Suppl 1):19–25.
11. Sathianathen NJ, et al. Negative predictive value of
multiparametric magnetic resonance imaging in the
detection of clinically signicant prostate cancer in
the prostate imaging reporting and data system era:
a systematic review and meta-analysis. Eur Urol.
2020;78(3):402–14.
12. Ahdoot M, etal. MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Engl J
Med. 2020;382(10):917–28.
13. Borofsky S, et al. What are we missing? Falsenegative cancers at multiparametric MR imaging of
the prostate. Radiology. 2018;286(1):186–95.
14. Johnson DC, et al. Detection of individual prostate
cancer foci via multiparametric magnetic resonance
imaging. Eur Urol. 2019;75(5):712–20.
15. Feuer Z, et al. Application of the PRECISION trial
biopsy strategy to a contemporary magnetic resonance imaging-targeted biopsy cohort-how many
clinically signicant prostate cancers are missed? J
Urol. 2021;205(3):740–7.
16. Brisbane WG, etal. Targeted prostate biopsy: umbra,
penumbra, and value of perilesional sampling. Eur
Urol. 2022;82(3):303–10.
17. Stavrinides V, et al. Five-year outcomes of magnetic resonance imaging-based active surveillance
for prostate cancer: a large cohort study. Eur Urol.
2020;78(3):443–51.
18. Olivier J, etal. Prostate cancer patients under active
surveillance with a suspicious magnetic resonance
imaging nding are at increased risk of needing treatment: results of the Movember Foundation’s global
action plan prostate cancer active surveillance (GAP3)
consortium. Eur Urol Open Sci. 2022;35:59–67.
19. Wibmer AG, et al. MRI-detectability of clinically
signicant prostate cancer relates to oncologic outcomes after prostatectomy. Clin Genitourin Cancer.
2022;20(4):319–25.
20. Li P, et al. Genes involved in prostate cancer progression determine MRI visibility. Theranostics.
2018;8(7):1752–65.
21. Le Nobin J, et al. Image guided focal therapy for
magnetic resonance imaging visible prostate cancer:
dening a 3-dimensional treatment margin based on
17 Staging Imaging forFocal Therapy ofProstate Cancer
185
magnetic resonance imaging histology co-registration
analysis. J Urol. 2015;194(2):364–70.
22. Priester A, etal. Magnetic resonance imaging underestimation of prostate cancer geometry: use of patient
specic molds to correlate images with whole mount
pathology. J Urol. 2017;197(2):320–6.
23. Isebaert S, et al. Multiparametric MRI for prostate
cancer localization in correlation to whole- mount
histopathology. J Magn Reson Imaging.
2013;37(6):1392–401.
24. Bratan F, etal. Inuence of imaging and histological
factors on prostate cancer detection and localisation
on multiparametric MRI: a prospective study. Eur
Radiol. 2013;23(7):2019–29.
25. Cornud F, etal. Tumor target volume for focal therapy
of prostate cancer-does multiparametric magnetic
resonance imaging allow for a reliable estimation? J
Urol. 2014;191(5):1272–9.
26. Rud E, et al. Detection of the index tumour and
tumour volume in prostate cancer using T2-weighted
and diffusion-weighted magnetic resonance imaging
(MRI) alone. BJU Int. 2014;114(6b):E32–e42.
27. Tan WP, etal. Utilization of focal therapy for patients
discontinuing active surveillance of prostate cancer:
recommendations of an international Delphi consensus. Urol Oncol. 2021;39(11):781.e17–24.
28. Tay KJ, etal. Patient selection for prostate focal therapy in the era of active surveillance: an international
Delphi consensus project. Prostate Cancer Prostatic
Dis. 2017;20(3):294–9.
29. Baco E, et al. Predictive value of magnetic resonance imaging determined tumor contact length for
extracapsular extension of prostate cancer. J Urol.
2015;193(2):466–72.
30. Mehralivand S, et al. A grading system for the
assessment of risk of Extraprostatic extension of
prostate cancer at multiparametric MRI. Radiology.
2019;290(3):709–19.
31. Grivas N, etal. Seminal vesicle invasion on multiparametric magnetic resonance imaging: correlation
with histopathology. Eur J Radiol. 2018;98:107–12.
32. de Rooij M, et al. Accuracy of magnetic resonance
imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. 2016;70(2):233–45.
33. Fraum TJ, etal. Prostate cancer PET tracers: essentials
for the urologist. Can J Urol. 2018;25(4):9371–83.
34. Wright GL Jr, etal. Expression of prostate-specic
membrane antigen in normal, benign, and malignant
prostate tissues. In: Urologic oncology: seminars
and original investigations, vol. 1. Elsevier; 1995.
p.18.
35. Maurer T, et al. Diagnostic efcacy of 68galliumPSMA positron emission tomography compared to
conventional imaging for lymph node staging of 130
consecutive patients with intermediate to high risk
prostate cancer. J Urol. 2016;195(5):1436–43.
36. Perera M, et al. Gallium-68 prostate-specic membrane antigen positron emission tomography in
advanced prostate cancer—updated diagnostic
utility, sensitivity, specicity, and distribution of
prostate-specic membrane antigen-avid lesions:
a systematic review and meta-analysis. Eur Urol.
2020;77(4):403–17.
37. Yaxley JW, et al. Risk of metastatic disease on
68gallium- prostate-specic membrane antigen positron emission tomography/computed tomography
scan for primary staging of 1253 men at the diagnosis
of prostate cancer. BJU Int. 2019;124(3):401–7.
38. Bahler CD, etal. Prostate specic membrane antigen
targeted positron emission tomography of primary
prostate cancer: assessing accuracy with whole mount
pathology. J Urol. 2020;203(1):92–9.
39. Koseoglu E, et al. Diagnostic ability of Ga-68
PSMA PET to detect dominant and non-dominant
tumors, upgrading and adverse pathology in patients
with PIRADS 4–5 index lesions undergoing radical prostatectomy. Prostate Cancer Prostatic Dis.
2021;24(1):202–9.
40. Donato P, et al. Improved specicity with 68 Ga
PSMA PET/CT to detect clinically signicant lesions
“invisible” on multiparametric MRI of the prostate:
a single institution comparative analysis with radical prostatectomy histology. Eur J Nucl Med Mol
Imaging. 2019;46:20–30.
41. Lopci E, etal. Prospective evaluation of 68Ga-labeled
prostate-specic membrane antigen ligand positron
emission tomography/computed tomography in primary prostate cancer diagnosis. Eur Urol Focus.
2021;7(4):764–71.
42. Emmett L, et al. The additive diagnostic value of
prostate-specic membrane antigen positron emission
tomography computed tomography to multiparametric magnetic resonance imaging triage in the diagnosis of prostate cancer (PRIMARY): a prospective
multicentre study. Eur Urol. 2021;80(6):682–9.
43. Emmett L, et al. The PRIMARY score: using
intraprostatic 68Ga-PSMA PET/CT patterns to
optimize prostate cancer diagnosis. J Nucl Med.
2022;63(11):1644–50.
44. Eiber M, etal. Simultaneous 68Ga-PSMA HBED-CC
PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70(5):829–36.
45. Grubmüller B, etal. PSMA ligand PET/MRI for primary prostate cancer: staging performance and clinical impact. Clin Cancer Res. 2018;24(24):6300–7.
46. Uprimny C, et al. 68 Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason
score predict the intensity of tracer accumulation in
the primary tumour. Eur J Nucl Med Mol Imaging.
2017;44:941–9.
47. Scheltema MJ, et al. Diagnostic accuracy of
68Ga-prostate-specic membrane antigen (PSMA)
positron-emission tomography (PET) and multiparametric (mp) MRI to detect intermediate-grade
intra-prostatic prostate cancer using whole-mount
pathology: impact of the addition of 68Ga-PSMA
PET to mp MRI.BJU Int. 2019;124:42–9.
48. Roberts MJ, et al. 68 Ga-PSMA PET/CT tumour
intensity pre-operatively predicts adverse pathological outcomes and progression-free survival inlocal-
186
M. B. Rothberg
ised prostate cancer. Eur J Nucl Med Mol Imaging.
2021;48:477–82.
49. Woo S, et al. Prostate-specic membrane antigen
positron emission tomography (PSMA-PET) for local
staging of prostate cancer: a systematic review and
meta-analysis. Eur J Hybrid Imaging. 2020;4:1–15.
50. Sathekge M, etal. 68 Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary
results on differences between black and white
south-Africans. Eur J Nucl Med Mol Imaging.
2018;45:226–34.
51. Roberts MJ, et al. Primary tumour PSMA intensity
is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy. Eur J Nucl Med Mol Imaging.
2022;49(9):3289–94.
52. Wang H, et al. PSMA-ligand uptake can serve as a
novel biomarker in primary prostate cancer to predict
outcome after radical prostatectomy. EJNMMI Res.
2021;11(1):76.
Part V
Prostate Imaging and Staging
Multiparametric MRI/TRUS Fusion
Biopsy, Outcomes,
andCommercial Systems
SoroushRais-Bahrami, OmarHayek,
BenjaminTavya, ThomasR.Williams,
andArdeshirR.Rastinehad
18
Introduction
For decades now, prostate cancer suspicion
driven by serum prostate-specic antigen (PSA)
elevation or abnormalities in digital rectal examination (DRE) have been conrmed with transrectal ultrasound (TRUS)-guided biopsy directed at
various regions of the prostate in a systematic
manner with guidelines dictating a standard-ofcare sampling of 10–14 cores, typically derived
in a 12-core extended sextant manner. These
S. Rais-Bahrami (*)
Department of Urology, University of Alabama at
Birmingham, Birmingham, AL, USA
Department of Radiology, University of Alabama at
Birmingham, Birmingham, AL, USA
O’Neal Comprehensive Cancer Center, University of
Alabama at Birmingham, Birmingham, AL, USA
e-mail: sraisbahrami@uabmc.edu
O. Hayek
Department of Urology, University of Alabama at
Birmingham, Birmingham, AL, USA
e-mail: oehaykek@uabmc.edu
B. Tavya · T. R. Williams
Smith Institute for Urology, Northwell Health,
New York, NY, USA
e-mail: tbenjamin5@northwell.edu;
TWilliams21@northwell.edu
A. R. Rastinehad
Smith Institute for Urology at Lenox Hill, Northwell
Health, Lake Success, New York, NY, USA
biopsies are, in essence, blinded and random by
nature as they are not directed toward a specic
target of heightened suspicion but rather to welldistributed geographic regions of the prostate
gland. The widespread use of PSA screening and
TRUS-guided systematic prostate biopsy resulted
in the overdiagnosis and overtreatment of lowrisk prostate cancers and the underdetection/
undertreatment of high-risk cancers, leading to
interventions without denitive survival benet
but amassing quality-of-life side effects derived
from treatment. The introduction of multiparametric magnetic resonance imaging (mpMRI)
has revolutionized the way we visualize prostate
cancer, as the use of this imaging technology aids
in the delineation and characterization of intraprostatic lesions suspicious for harboring malignancy. Extending beyond mpMRI as a diagnostic
tool, the transformative technique of MRI/TRUS
fusion-guided biopsy allows for directed biopsy
sampling of MRI suspicious regions of interest in
addition to the systematic biopsy sampling an
option for a more precise prostate biopsy.
TRUS offers the ability to acquire real-time
imaging and is readily utilized in outpatient urology practices. However, b-mode ultrasound is
limited by poor spatial resolution and low sensitivity for colocalization of prostate cancer foci, as
cancer lesions can often appear isoechoic on
TRUS imaging, making them difcult to distinguish from the surrounding background [1].
Conversely, high quality mpMRI presents pros-
© 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_18
189
S. Rais-Bahrami et al.
tatic lesions with striking detail and possesses
high sensitivity, yet does not offer the capability
for real-time image acquisition and guidance for
biopsy in a timely or cost-efcient manner.
Developers have strategically created softwarebased “fusion” platforms to overlay threedimensional (3D) MRI and TRUS imaging of the
prostate, thus allowing individuals performing
biopsy to take advantage of the essential information and features offered by both modalities [2].
Utilizing these fusion biopsy platforms, a targeted
fusion biopsy allows for sampling of specic
regions of interest within the prostate with these
lesions pre-identied on MRI, thus providing a
means of adding to or potentially circumventing
the need for systematic but functionally random
biopsies throughout different regions of the gland.
Herein, we provide a comprehensive review of
the current MRI/TRUS fusion-based targeting
strategies, indications as well as general workow for the fusion biopsy technique, and an overview of commercially available software-based
registration platforms with their respective
strengths, limitations, and reports of their clinical
operational outcomes.
Magnetic Resonance ImagingBased Targeted Biopsy Techniques
Three methods of MRI guidance are currently
utilized for the performance of targeted prostate
biopsy: cognitive fusion, direct MRI-guided
biopsy (“in-bore” biopsy), and MRI/TRUS
software- based fusion-guided biopsy through
either transrectal or transperineal (TP) needle
sampling approaches [3].
Cognitive Fusion
Cognitive fusion, also referred to as visual targeted biopsy, is a technique in which the ultrasound operator performing the biopsy procedure
simply directs the biopsy needle in the general
region of the prostate gland where a previously
acquired MRI demonstrates a region of interest
suspected to have cancer risk [4]. For this
approach, prostate indication mpMRI is acquired
prior to a TRUS-guided biopsy procedure, and
“cognitive registration” is performed using
knowledge from the MRI, which is often displayed in the procedure suite demonstrating the
localization of the suspicious region of interest.
Colocalization with this region of interest is done
by the biopsy proceduralist with TRUS to guide
the biopsy needle to the appropriate area or areas
of the prostate with MRI-identied cancersuspicious lesions. This method is appealing as it
is simple, time efcient, and does not require any
additional capital acquisition of equipment
beyond the traditional TRUS-directed biopsy
setup often present in outpatient urology ofces.
The mpMRI is typically not a cost burden to the
urologist performing the biopsy but does require
high-delity diagnostic MRI with a prostatespecic protocol now widely available at most
hospitals and high-volume imaging centers.
Furthermore, cognitive fusion does not necessitate signicant upfront capital investment in software fusion technology or additional training
modules/sessions with previously unfamiliar
hardware and software.
Several studies have compared cognitive
fusion to the conventional systematic biopsy
technique and also to fusion-targeted biopsies
using software-based registration platforms.
Haffner etal. showed, in a cohort of 555 patients
with suspicion of prostate cancer, that cognitive
fusion biopsy had higher detection accuracy of
clinically signicant prostate cancer relative to
extended systematic biopsy involving 10–12
cores (p < 0.001) [5]. Furthermore, targeted
biopsy with cognitive registration detected 16%
more grade 4/5 cancers and more accurately
quantied tumor burden (p= 0.002). Similarly,
Park etal. demonstrated in a prospective evaluation in patients with elevated PSA and no prior
biopsy history that cognitive fusion had higher
cancer detection rates (29.5% vs. 9.8%, OR 3.9,
p=0.03) relative to TRUS biopsy alone [6]. In
the prospective PROFUS trial, Wysock et al.
compared targeted biopsy outcomes between
MRI/ultrasound fusion biopsy and cognitive
fusion biopsy and found similar cancer detection
rates for all cancers (32.0% vs. 20.3%, p=0.1374)
and Gleason sum ≥7 cancers (26.7% vs. 15.1%,
p=0.0523) [7]. Another study compared targeted
18 Multiparametric MRI/TRUS Fusion Biopsy, Outcomes, andCommercial Systems
191
MRI/TRUS fusion biopsy (both cognitive fusion
and software-based) to TRUS-guided systematic
biopsy in a prospective trial of 95 patients who
had suspicious images at mpMRI [8]; they found
that positivity rates for prostate cancer (69% vs.
59%, p=0.033) and sampling quality (maximum
cancer length per core, Gleason grade) were
superior with targeted biopsy relative to systematic biopsy, regardless of visual (cognitive)-based
registration or software-assisted registration.
Nevertheless, it appears that results with cognitive fusion biopsy are mixed, as few studies
have shown cognitive fusion biopsy to be no better than systematic TRUS biopsy [9, 10].
Delongchamps etal. tested the accuracy of visual
targeted biopsy in 127 patients and found no difference when compared to systematic biopsy
with respect to cancer detection rate (p= 0.66)
[9]. Examining Level I evidence comparing cognitive fusion biopsy to systematic 10- to 12-core
TRUS biopsy, Tonttila etal. found no difference
in cancer detection rates for both overall (64% vs.
57%, p=0.5) and clinically signicant (55% vs.
45%, p=0.8) cancers; therefore, the authors concluded that additional prostate MRI before prostate biopsy did not add signicant value [10].
However, rather than inferring that no benet is
achieved from MRI, this study may signify that
there is limited benet in biopsy-naïve patients.
Finally, in a direct comparison of MRI/TRUS
fusion versus cognitive registration, one study
found cognitive registration to be inferior to
software- based MRI/TRUS fusion, as fewer than
50% of csPCa lesions were successfully sampled
with cognitive registration, regardless of experience level [11]. This was followed by a randomized controlled trial by Izadpanahi et al., who
reported both overall and clinically signicant
cancer detection rates higher in their group of
men undergoing software-based MRI/TRUS
fusion targeted biopsy (44.4% and 33.3%, respectively) compared to those undergoing cognitive
fusion targeted biopsy (31.0% and 19.0%, respectively [12]).
Cognitive fusion biopsy is heavily operator
dependent and requires extensive knowledge of
prostate gland anatomy in order to extrapolate
3-dimensional lesion localization from MRI to
TRUS without an actual overlay and software-
based coregistration of the two imaging modalities used for guidance and targeting. One study
highlights the difculty in performing visual registration, as TRUS 2D images project in a fanshaped pattern and can be markedly different
from the axial imaging plane on MRI, making it
difcult to accurately estimate lesion location
during TRUS biopsy [13]. This imaging disparity
is most evident in anterior base and anterior apical lesions. Inaccurate lesion location estimation
can be partially overcome by utilization of anatomical landmarks, such as prostatic cysts, benign
prostatic hyperplasia (BPH) nodules, and/or calcications as internal reference points to help
further guide the biopsy needle relative to these
natural ducial markers within the gland.
However, these “internal ducials” are not always
present, and heterogeneous echogenicity on
TRUS may falsely lead the reader to misregister
images, whereby relatively small differences in
coregistration of the MRI to real-time TRUS can
dramatically alter the results and yield of the targeted biopsy in dening accurate pathology of
the lesion identied as suspicious on mpMRI.As
a nal limitation, cognitive fusion methods do
not offer the ability to track and record biopsy
coordinates for later reference, whether for resampling in the future or personalizing guidance of
treatment as have been reported [14–17].
In-Bore MRI-Guided Biopsy
In-bore MRI-guided biopsy entails acquiring
biopsy samples within the MRI gantry under
direct guidance after prostate lesions have been
pre-identied, often with a prior diagnostic prostate indication mpMRI.During the biopsy procedure, the patient is placed prone in the MRI
gantry, and biopsy needles are directed toward
suspicious lesions via a transrectal or transperineal (TP) approach [18]. Core tissue samples are
obtained with serial MRI scans to conrm biopsy
needle placement [19]. The primary advantages
of this approach are precise lesion sampling due
to the elimination of registration error between
MRI and TRUS and less total number of cores
necessary relative to systematic 10–14 core
biopsy schemas, as typically through this in-bore
192
S. Rais-Bahrami et al.
MRI targeted biopsy approach, only suspicious
lesions are targeted for sampling [20].
In a study of 100 patients with prior negative
TRUS-guided systematic biopsy along with a
persistently elevated or rising serum PSA, and at
least one suspicious lesion found on mpMRI,
Roethke et al. found a cancer detection rate of
52% overall and 80.8% for csPCa utilizing the
in-bore MRI-guided biopsy technique [21].
Similarly, another report demonstrated the utility
of MRI-guided in-bore biopsy in patients with
prior negative biopsies and biopsy-naïve patients,
with overall cancer detection rates of 43.1% and
55.6%, respectively [22]. Hambrock etal. compared the ability of in-bore mpMRI-guided biopsies versus 10-core TRUS biopsy to match true
Gleason grade as determined by the gold standard of radical prostatectomy specimens; they
showed that the highest Gleason grade from inbore biopsy matched nal pathology in 88% (30
of 34) patients, whereas the highest Gleason
grade from 10-core TRUS biopsy matched nal
pathology in only 55% (35 of 64) of patients
(p=0.001) [23].
Despite initial success with several studies
demonstrating its efcacy, in-bore MRI-guided
biopsy has not been embraced clinically due to
several limitations. First, the procedure is relatively lengthy and often requires sedation as
patients have to remain still for the duration of
the procedure. Moreover, the technique is costly
and requires trained personnel and specialized
MR-safe equipment, which includes everything
used for the biopsy procedure as well as the
administration of anesthesia [24]. Finally, the
biopsy is performed in the radiology department
and thus interferes with the normal day-to-day
workow of using the MRI device, leading to a
lost opportunity cost when other patients cannot
be undergoing higher throughput diagnostic
MRI, which is more nancially lucrative for the
institution. Its unique benet would be in patients
unable to undergo TRUS (e.g., abdominoperineal
resection), where an in-gantry transperineal targeted approach to prostate biopsy would provide
reliable imaging and targeting of suspicious
lesions within the prostate [25]. Due to the limitations often outweighing the benets, although
highly accurate and utilized in some centers, this
technique of in-bore biopsy in high-eld magnets
used for diagnostic mpMRI has not been broadly
adopted for clinical use for most men undergoing
targeted biopsy of MRI suspicious prostate
lesions [26].
Recently, there has been a pivot to allow for
“in-bore” MRI-guided prostate biopsy procedures in a point-of-care, ofce-based low-eld
strength MRI apparatus. The Promaxo MRI system is a novel point-of-care MRI system that
allows urologists to perform intraprocedural
MRI biopsies in the ofce setting, fusing preprocedural diagnostic mpMRI used for lesion
identication with the low-eld strength procedural MRI. This provides many of the advantages of traditional in-bore biopsies while
allowing patients and their caregivers to circumvent the logistical and monetary constraints
posed by high-eld strength MRI devices for
true in-bore biopsy. While this technology was
FDA approved for use in image-guided prostate
interventions since 2021, there have not been
robust clinical trials comparing the diagnostic
yield using this technology versus softwarebased fusion or cognitive fusion targeted biopsy
techniques. However, a 2021 study conducted
by Promaxo demonstrated the feasibility of this
system by comparing navigation errors during
Promaxo- guided biopsies of prostate models to
ground truths obtained by traditional 1.5 T
MRIs [27]. This study found that the average
navigational error was less than 3mm, below
the generally accepted threshold of 5 mm for
image-guided prostate biopsy modalities and
similar to the reported 2.4mm spatial misregistration potential of one of the software-based
MRI/TRUS fusion platforms [28]. The Promaxo
MRI system certainly shows promise and confers many benets over other MRI guided
biopsy approaches with high eld strength magnets investigated and used to date as it would not
incur the degree of capital outlay and lost revenue from displacing diagnostic imaging patients.
Nevertheless, further comparative studies to
other MRI targeting approaches for prostate
biopsy are needed before this technology is
likely to be widely adopted.