Download Role of magnetic resonance imaging in the

Editorial
Role of magnetic resonance imaging in the diagnosis
and treatment of prostate cancer
N. Criøan1, Iulia Pop1, Ioana Hiriscau1, I. Coman1,2
1
Urology Department, Municipal Hospital, Cluj-Napoca, Romania
2
University of Medicine and Pharmacy „Iuliu Haieganu“, Cluj-Napoca, Romania
Abstract
Prostate cancer is the second most common cause of oncological mortality in men. The screening based on digital
rectal examination and determination of PSA level is still controversial because it has low specificity for clinically significant prostate cancer. Also, ultrasound-guided prostate biopsy is criticized due to its poor detection rate and many
false negative results. In this context, magnetic resonance imaging comes as the missing puzzle piece because of the
accurate information about the localization, characterization and staging of prostate cancer, the advantages of guiding prostate biopsy and focal therapy, and the possibility to assist and improve the surgical technique. The European
Society of Urogenital Radiology argue cogently that magnetic resonance imaging should be an integral part of the
diagnosis and treatment of prostate cancer.
Keywords: magnetic resonance imaging, MRI-guided interventions, prostate cancer
Correspondence: Iulia Pop
str. Tabacarilor nr. 11
Urology Department, Municipal Hospital, Cluj-Napoca, Romania
0744374996, [email protected]
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• Value of prostate MRI in the diagnosis of prostate
cancer
The diagnosis of PC is based nowadays on three
steps: determination of PSA level, digital rectal examination and prostate biopsy. Even though it is used
worldwide, the antigen screening still remains controversial, having poor specificity for significant cancer [2];
at least 60-70% of initial biopsies in patients with high
PSA levels are negative and up to 45% of diagnosed
PC are low-risk [3]. Digital rectal examination and transrectal ultrasound-guided prostate biopsy have also
poor sensitivity for the diagnosis of PC. The main challenge that arises is to find the perfect balance between
the overdiagnosis and overtreatment of patients with
indolent PC that would be suitable for active surveillance, and the underdiagnosis and undertreatment of
patients with aggressive PC.
Advances in magnetic resonance imaging show
promise for improved detection and characterization
of PC, using a multiparametric approach, which combines anatomical and functional data [4]. Multiparametric MRI (mpMRI) includes a combination of highresolution T2-weighted images (T2WI), and at least two
functional MRI techniques (dynamic contrast enhancement – DCE-MRI, diffusion-weighted imaging – DWIMRI, and spectroscopy). T2-weighted imaging is the
foundation of mpMRI, as it provides high-resolution
anatomical images of the prostate. Normally, the peripheral zone of the prostate has high signal intensity
in T2WI – if PC is present, it appears as a focus with low
signal intensity. Diffusion-weighted imaging (DWI)
measures the diffusion of water molecules through
different tissues. Prostate cancer exhibits a reduced
diffusion of water compared to normal prostate tissue
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due to its high cellularity and disruption of interstitial
spaces and planes through which water normally diffuses – from this acquisition, apparent diffusion coefficient (ADC) maps of the prostate are then derived.
Dynamic contrast-enhanced imaging (DCE-MRI) is
based on the intravenous administration of gadolinium, followed by a series of rapid sequential scans. Each
scan demonstrates a map of perfusion for every spatial
region of the prostate at various moments in time. This
information can be plotted graphically to create a perfusion vs time curve, which shows how rapidly the gadolinium uptake and the wash-out were. If PC is present,
it will appear as a zone with early and intense contrast
enhancement, followed by rapid wash-out. Magnetic
resonance spectroscopy is a functional technique
that measures metabolite levels in the prostate. Prostate cancer is characterized by a high concentration of
choline and creatine, and low concentration of citrate
– opposed to the normal tissues [5].
When combining at least three MRI sequences, the
sensitivity and specificity for the detection of tumors
larger than 0.2 mL can reach 75% and 94%, respectively, with more than 90% accuracy [6].
Editorial
Introduction
Prostate cancer (PC) is the second most common
cause of oncological mortality in men. In Romania, the
prevalence of prostate cancer reaches 3%, when using
digital rectal examination and determination of PSA
level for screening. As stated in the results of the CLOSER screening program that took place in Cluj-Napoca in
2005, the detection rate of localized PC is 41.9% [1]. The
rise in the diagnosed number of patients with localized
PC, not only in Romania, allowed for the development
of new techniques for the diagnosis and curative treatment of the disease. Magnetic resonance imaging (MRI)
is one of the most promising techniques that has been
repeatedly proven to have a major importance in the
diagnosis and treatment of PC.
Fig. 1 – T2WI – an
area with low signal
intensity in the
peripheral zone of
the prostate
Fig. 2 – DWI – an
area with low signal
intensity in the left
lobe because of the
restricted water
diffusion
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Editorial
a more effective prostate MRI, improving the detection
of clinically significant cancer [8].
Fig. 3 – DCE-MRI
– important
enhancement in
the peripheral zone
after gadolinium
administration
Fig. 4 – Spectroscopy
– high concentration
of choline and low
concentration of
citrate, characteristic
for prostate cancer
In addition to the detection of prostate cancer,
mpMRI shows to be a useful tool in evaluating the clinical importance of the diagnosed cancer. It has been
stated many times that the ADC values, generated
from the DWI-MRI acquisition, correlate with the Gleason score. By assessing the aggressiveness of PC, mpMRI before or even initial biopsy can accurately select
patients who require immediate biopsies and those in
whom biopsy could be deferred, can target prostate
biopsies in order to have an accurate diagnosis and
also can be a factor of importance when identifying patients suitable for active surveillance.
In 2012, the European Society of Urogenital Radiology formulated a series of guidelines for the MRI evaluation of the prostate. They suggest that the MRI data
would be more helpful for the other specialities if presented as a score – PI-RADS (similar to BI-RADS, used
for breast cancer), which estimates the probability of a
lesion to be clinically significant (score 1: clinically significant disease is highly unlikely to be present, score
2: clinically significant cancer is unlikely to be present,
score 3: clinically significant cancer is equivocal, score
4: clinically significant cancer is likely to be present,
score 5: clinically significant cancer is highly likely to be
present). The PI-RADS score has shown good to moderate interreader agreement and enables standardized
evaluation of prostate mpMRI, with high sensitivity and
negative predictive value [7]. It may also contribute to
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• MRI for the staging of prostate cancer
When choosing the most suitable therapeutic option for a patient with diagnosed PC, a decisive information is the staging of the tumor. Multiparametric
MRI has proven to be useful in evaluating the local
staging of PC. When using multiplanar reconstruction
and including both, direct and indirect signs of extracapsular extension, the sensitivity and specificity for
T3a stage of T2WI reaches 84% and 89%, respectively
[9]. Less experienced readers have been shown to benefit most from the use of 3D spectroscopy in association with T2WI, which significantly improved the accuracy of staging and the area under the ROC curve [10].
Also, the combination of DCE-MRI and T2WI has shown
improved performance in predicting extracapsular extension than either technique alone [11]. But the best
predictor of pT3 tumors is endorectal coil MRI [12].
Dynamic-contrast enhancement MRI and DWI-MRI,
along with T2WI are used for detecting T3b stage and
can add additional value to current nomogram for the
prediction of seminal vesicle involvement [13].
Unfortunately, MRI remains disappointing regarding the lymph node staging of prostate cancer, with a
sensitivity of only 30% [14]. Lately, a new technique for
the MRI evaluation of lymph nodes in prostate cancer
shows promising results, but it is not yet introduced in
the clinical practice. Combined ultrasmall superparamagnetic particles of iron-oxide enhanced (USPIO) and
DWI-MRI has been shown to be an accurate method
for detecting metastases in normal-sized pelvic lymph
nodes of patients with PC (sensitivity and specificity up
to 75% and 96%, respectively [15].
• MRI and prostate biopsy
Ultrasound-guided prostate biopsy, either transrectal or perineal, is the method of choice for the confirmation of PC in patients with clinical (suggestive digital
rectal examination) or biological suspicion (high level
of PSA). Many professionals criticize this method because of the low detection rate (20-40%) [16] and of
the false negative results (20%) [17]. The limitations
of the ultrasound-guided prostate biopsy are due to
the fact that it is based on an imaging technique (transrectal ultrasound) with low sensitivity and specificity
in identifying the malignant prostate lesions [18], but
also due to the fact that the choice of biopsied areas
and the biopsy needle path are majorly biased by the
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There are two aspects that require standardization
in order to have comparable reporting of the results of
MRI-guided prostate biopsies:
1. Indication – which patients can benefit more from
this biopsy?
2. The tissue harvesting technique
The MRI-guided tissue harvesting technique can
lead to specific errors that can alter the quality of the
histopathological outcome: imperfect overlay of MRI
images with ultrasound (when peforming ultrasoundguided biopsy) and the change in the position of the
prostate due to the presence of the endorectal coil, to
the movement of the biopsy needle and to the patient
movement during the procedure.
In order to improve the tissue harvesting technique,
there have been identified three types of biases that
can alter the quality of the MRI targeted biopsies:
1. Target movement – the difference between planned
and real time biopsy
2. Error in the positioning of biopsy needle – the difference between the planned targeted biopsy and
the trajectory of the biopsy needle
3. Biopsy error – the difference between the targeted
real biopsy and the trajectory of biopsy needle
The robotic system developed by Xu et al has reported the following results for the target movement,
error of positioning and biopsy error: 5.4, 2.2 and 5.1
mm, respectively [24].
A prospective study evaluated the 12-core systematic prostate biopsy in comparison with mpMRItargeted biopsy (cognitive and ultrasound-MRI fusion
biopsy). The detection rate was 69% for systematic biopsy and 59% for MRI-targeted biopsy. However, when
assessing the detection rate for the clinically significant
PC (malignant tissue on any biopsy longer that 3 mm
or with Gleason grade higher than 3), they noticed
that the MRI-targeted biopsy detected 67% of cases, in
comparison with 52% for systematic biopsy [25].
Another study reported also a detection rate for
clinically significant PC of 87% for MRI-guided prostate biopsy, higher than of the systematic and targeted
prostate biopsies [26].
A very useful application of MRI-guided prostate
biopsy could be the biopsy of patients with previous
negative ultrasound-guided biopsies, but high PSA
values or abnormal digital rectal examination. In these
cases, the confirmation rate for PC of MRI-guided biopsy can reach a sensitivity and specificity of 93% and
94.4%, respectively. This means an improvement in the
detection rate for PC of 40%, in comparison to 20-35%
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Editorial
subjectivism of the medical examiner.
Therefore, the need for improved diagnosis in PC
has become mandatory for two reasons: the first is the
need for a better detection and localization of malignant areas of the prostate, and the second - the need
for increased precision during the act of harvesting
the tissue fragments by exact biopsy needle guidance
in targeted areas. Magnetic resonance imaging is a
technique that improves mostly the first aspect: the
detection and localization of prostate cancer, as stated
before in this review. This imaging method has the advantages of a high spatial resolution, excellent contrast
for soft tissues and the possibility for volumetric images
assessment [19]. The limitation of MRI is technical and
related to the second aspect: does it have the ability
to assist and guide the needle during prostate biopsy?
As a result, most studies tried to develop various techniques to assist prostate biopsy by overlapping the MRI
images with ultrasound, but many have found obstacles when superposing the prostate mapping. The first
MRI-guided prostate biopsy was reported in 2000 and
was performed transperineally, with the patient under
general aenesthesia, in litothomy position [20].
There are three possibilities for performing prostate
biopsy: targeted prostate biopsy (the biopsy is ultrasound-guided, but based on the coordinates offered
by the MRI images), ultrasound-MRI fusion guidedbiopsy (the biopsy is ultrasound-guided, but the archived MRI images are overlapped onto the ultrasound
during biopsy) and MRI-guided prostate biopsy. Of
all three possibilities, MRI-guided prostate biopsy has
the highest detection rate (80%), in comparison with
46.2% for MRI-ultrasound fusion guided biopsy and
33.3% for MRI-targeted biopsy [21].
Probably the most efficient method is MRI-guided
transperineal prostate biopsy, because it allows a more
effective harvesting of tissue from areas with high incidence of cancer, but also from the anterior zone of the
prostate, all these with a lower rate of septic complications. The disadvantages of this type of biopsy are:
more intense pain, that usually requires general aenesthesia, which involves a more complex logistics and
higher costs of the procedure [22].
Prostate MRI might reduce the number of patients
that should really undergo a prostate biopsy. The effectiveness of the method is defined by the ratio between
the number of clinically relevant diagnosed PC patients
and the number of biopsied cases. Targeted biopsy has
been shown to have o higher accuracy (70%) than the
standard (40%) [23].
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Editorial
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when performing the second ultrasound-guided biopsy [27] [28].
• MRI and focal therapy for prostate cancer
Focal therapy represents the eradication of the malignant tissue inside the prostate and the preservation
of the non-malignant tissue in order to maintain the
genitourinary function as much as possible [29]. The
efficiency of the focal therapy is majorly influenced by
the exact mapping of the malignant areas. Multiparametric MRI allows a fair localization of cancer inside the
prostate, so it can become a tool to assist the focal therapies: laser ablation, high-intensity focused ultrasound
(HIFU), cryosurgery, brachytherapy, microwave ablation and radiofrequency ablation. The imaging method
can allow the exact localization and the selective ablation of malignant areas inside the prostate [30].
Magnetic resonance imaging has four key roles in
the guidance of focal therapy: identification and characterization of the neoplasic tissue inside the prostate,
positioning of the device and monitoring the ablation
of cancer nodules [31].
In 2012, the first case of focal therapy by MRI-guided HIFU was reported. The procedure was performed
in one-day-surgery system, the patient was discharged
the same day, without uretro-vesical catheter and postprocedural complications. The efficacy of the therapy
was assessed by the identification of devascularized
areas in the prostate. Before treatment, the same areas
were positive at biopsy and identified on the MRI images. The follow-up implied a repeat biopsy at 6 months
after the procedure [32].
Subsequently, there were published the results
of a series of 26 patients with prostate cancer treated
by HIFU, for whom the selection of the ablated areas
was based on the information from transperineal biopsy and from mpMRI. Three types of focal ablation
were performed: quadrant ablation, hemi-ablation and
hemi-ablation with contralateral extension [33].
In another series, the efficiency of this method was
assessed for 5 patients, that underwent radical prostatectomy after MRI-guided focal therapy. The histopathological examination showed no residual malignant
tissue in the areas treated by HIFU. However, outside
the treated areas the pathologist identified significant
malignant tissue that was not reported by the pretreatment MRI examination [34].
The advantages of MRI localization of the malignant
areas in the prostate were used also to assist cryotherapy. In 2012, the results of a series of 10 patients that
Revista Românæ de Urologie
underwent cryotherapy was published. For these patients, the procedure was monitored by real-time MRI.
This technique seemed to be feasible, MRI allowed an
exact positioning of the cryoprobes in real-time, but
also an excellent monitoring of the developing ice ball
[35].
Another MRI-guided focal therapy for PC is the
transperineal laser ablation. In a study form 2013 on 9
patients with low-risk PC, this procedure was feasible
and did not associate urinary complications. The MRI
follow-up after the therapy showed a hipovascular
defect of the treated areas for 8 patients and the MRIguided biopsy of these areas revealed residual cancer
for 2 patients [36].
• Role of prostate MRI in surgical planning
According to the Guidelines of the European Association of Urology in 2013, the treatment of choice
in localized PC is radical prostatectomy (RP), which can
be performed by open, laparoscopic or robotic approach. Regardless the type of approach used, RP has
three main challenges: to ensure the oncological control of the disease, but also to maintain the uro-genital functionality – potency and continence. In order to
overcome these challenges, the surgeon must perform
a very cautious dissection, with regard to the oncological principles, and also a high-quality nerve-sparing
and uretro-vesical anastomosis.
Advances in prostate MRI may provide important
information for the surgeon and can become a useful
tool for pre-treatment surgical planning. There are at
least 3 steps in which the information offered by MRI
may improve the surgical decisions: predicting the surgical difficulty, assessing the extracapsular spread of
PC/evaluation of neuro-vascular bundles involvement
and prediction of post-operative continence.
1. Predicting the surgical difficulty
During RP, especially when performed by robotic
approach, access to the deep pelvis and adequate
exposure is critical, given the close proximity of vital
and anatomic structures, on which the functional outcomes depend. The pelvis of the man is very narrow
in most cases and, therefore, may restrict some of the
important maneuvres during RP. The limitations come
from the pelvic anatomy, but also from the prostate dimensions [13].
Mason et al in 2010 [37] published a study on 76 patients evaluated by endorectal MRI before robotic RP.
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2. Evaluation of the neuro-vascular bundles
involvement
In the last decades, the number of patients diagnosed with localized PC increased due to the introduction of screening programs (based mostly on determining the serum PSA levels) and the advances in imaging
techniques. Nowadays, there are numerous options for
curative treatment of localized PC, so efforts have been
made to preserve also the sexual function after RP.
Singer et al noted that men undergoing treatment for
prostate cancer were willing to exchange an approxi-
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mate 20% chance of cure for an increased prospect of
remaining potent after therapy [39]. The surgeon must
now find the perfect balance between performing
nerve-sparing surgery and ensuring negative surgical
margins. The decision on whether to preserve or not a
neuro-vascular bundle is based mainly on the presence
and location of extracapsular extension.
Multiparametric endorectal MRI, which combines
the conventional and the functional techniques, has
been proven to provide a very good depiction of pelvic
anatomy and prostate, being useful in predicting the
presence of cancer as well as extracapsular extension
and involvement of the neuro-vascular bundles.
A study published by Labanaris et al in 2009 analyzed the role of multiparametric MRI in the decision
on whether nerve-sparing should or should not be
performed during RP. The sensitivity, specificity and
accuracy rate of mpMRI were 92%, 100% and 100% for
extracapsular extension, seminal vesicles involvement
and neuro-vascular bundles involvement, respectively.
The conventional and functional MRI favoured NVB
preservation in 22 patients (67%) with a high clinical
probability of extraprostatic disease, and opposed
NVB preservation in 11 patients (33%) with a low clinical probability of extraprostatic disease. Based on the
final histopathological findings, the surgical plan was
successfully changed in all patients. These results were
higher than other published international standards,
but in the authors’ opinion this might be the result of
the high experience of the reader [40].
In conclusion, multiparametric MRI is one of the
most sensitive preoperative clinical staging methods
for selective patients, and extremely useful for identifying candidates for nerve-sparing RP.
Editorial
The parameters used for predicting surgical difficulty
were: estimated blood loss (EBL), transfusion rates, operative time (OT) and positive surgical margin status.
Patients who underwent robotic RP with prostate volume < 35mL and with a PV-to-PCI (prostate volume-topelvic cavity index) ratio of < 6 had significantly less
blood loss and shorter OT. Higher prostatic transverse
diameter, prostate volume, and PV-to-PCI ratio were
also significantly correlated with OT and increased EBL.
This suggests that patients with small prostates within
large pelvises are predicted to have an easier surgery
than those with large prostates in small pelvises. Factors that were significantly correlated with positive surgical margins were PSA and pelvic cavity index, which
acts as a surrogate for working space in the pelvis for
robotic arms. Mason also observed that the patients
with positive apical margins had a pelvic cavity index
that was significantly smaller than those with positive
margins at other sites (6.53 vs 8.24, Student’s t-test,
P<.0085). In another study published by Matikainen
et al in 2009, apical prostate depth (defined as the craniocaudal distance from the most proximal margin of
the symphysis pubis to the level of the distal margin of
the prostatic apex as measured on the mid-sagittal T2weighted sequence image) was found to be an independent risk factor for apical positive surgical margins
at RP [38]. In other words, patients who had positive
apical margins had more surgically challenging and
deeper pelvises than those who had positive margins
at other sites.
In conclusion, endorectal coil MRI can provide accurate information regarding the dimensions of the deep
pelvis, the pelvic inlet, and the prostate. The MRI can
act as a navigation tool intraoperatively using its anatomic information. Obtaining pre-operative MRI may
help with surgical planning and may alert the surgeon
to the difficulty of the case.
3. Prediction of post-operative continence
In addition to impotency, the urinary incontinence
is another outcome that alters the quality of life of
patients that undergo surgery for PC. Membranous
urethral length, which can be measured using conventional endorectal MRI on the sagittal and coronal images, from the prostatic apex to the urethra at the level
of the penile bulb, has been identified as a factor that
may contribute to post-RP urinary continence. Paparel
et al and Coakley et al published two studies that assess the importance of urethral length (measured preoperatively and in some cases, post-operatively) in the
regaining of continence after the surgery. Both studies
suggest that longer membranous urethral length on
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pre-operative MRI is associated with increased rate of
recovery and overall continence [41] [42] .
Fig. 5 Measurement
of the membranous
urethral length on
T2WI in sagittal
section
The assessment of urethral length using MRI is a
tool that may assist the surgeon at the step of urethral
incision. For patients with longer membranous urethra
and the tumor localized at the apex of the prostate, the
urethral incision may be performed at distance from
the apex, in order to ensure the oncological control of
PC with negative surgical margins, but also to preserve
the functional outcomes.
Conclusion
In conclusion, mpMRI can offer much needed information about the presence, localization, aggressiveness and staging of prostate cancer, can assist prostate
biopsy by selecting patients suitable for biopsy or by
guiding of the biopsy needle, can also assist the focal therapies in order to preserve healthy tissue and
urogenital functionality and can be an important factor when planning the surgery. Magnetic resonance
imaging contributes to the decision of performing
nerve-sparing or not and can designate the areas with
high suspicion of extracapsular extension in order to
retrieve tissue for frozen sections. The surgical planning assisted by MRI can predict and warn about the
difficulty of the procedure, and also can improve the
oncological (status of the surgical margins) and functional results (potency, continence). Latest advances
in magnetic resonance imaging make this method a
real necessity in the proper diagnosis and treatment of
prostate cancer.
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