Transrectal Ultrasound (US), Contrast-enhanced US, Real-time Elastography, HistoScanning, Magnetic Resonance Imaging (MRI), and MRI-US Fusion Biopsy in the Diagnosis of Prostate Cancer

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus

Review – Prostate Cancer

Transrectal Ultrasound (US), Contrast-enhanced US, Real-time Elastography, HistoScanning, Magnetic Resonance Imaging (MRI), and MRI-US Fusion Biopsy in the Diagnosis of Prostate Cancer Timur H. Kuru a,*, Jurgen J. Fu¨tterer b, Jonas Schiffmann c, Daniel Porres a, Georg Salomon c, Ardeshir R. Rastinehad d a

Department of Urology, RWTH University, Aachen, Germany; b Department of Radiology, Radboud University, Nijmegen, The Netherlands; c Martini Clinic,

Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany; d Icahn School of Medicine, Mount Sinai, NY, USA

Article info

Abstract

Article history: Accepted June 2, 2015

Context: Debates on overdiagnosis and overtreatment of prostate cancer (PCa) are ongoing and there is still huge uncertainty regarding misclassification of prostate biopsy results. Several imaging techniques that have emerged in recent years could overcome over- and underdiagnosis in PCa. Objective: To review the literature on transrectal ultrasound (TRUS)-based techniques (contrast enhancement, HistoScanning, elastography) and magnetic resonance imaging (MRI)-based techniques for a nonsystematic overview of their benefits and limitations. Evidence acquisition: A comprehensive search of the PubMed database between August 2004 and August 2014 was performed. Studies assessing grayscale TRUS, contrastenhanced (CE)-TRUS, elastography, HistoScanning, multiparametric MRI (mpMRI), and MRI-TRUS fusion biopsy were included. Publications before 2004 were included if they reported the principle or the first clinical results for these techniques. Evidence synthesis: Grayscale TRUS alone cannot detect PCa foci (detection rate 23– 29%). TRUS-based (elastography) and MRI-based techniques (MRI-TRUS fusion biopsy) have significantly improved PCa diagnostics, with sensitivity of 53–74% and specificity of 72–95%. HistoScanning does not provide convincing or homogeneous results (specificity 19–82%). CE-TRUS seems to be user dependent; it is used in a low number of highvolume centers and has wide ranges for sensitivity (54–79%) and specificity (42–95%). For all the techniques reviewed, prospective multicenter studies with consistent definitions are lacking. Conclusions: Standard grayscale TRUS is unreliable for PCa detection. Among the techniques reviewed, mpMRI and MRI-TRUS fusion biopsy seem to be suitable for enhancing PCa diagnostics. Elastography shows promising results according to the literature. CETRUS yields very inhomogeneous results and might not be the ideal technique for clinical practice. The value of HistoScanning must be questioned according to the literature. Patient summary: New imaging modalities such as elastography and magnetic resonance imaging/transrectal ultrasound fusion biopsies have improved the detection of prostate cancer. This may lower the burden of overtreatment as a result of more precise diagnosis. # 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Associate Editor: James Catto Keywords: Prostate cancer Imaging Detection Review

* Corresponding author. Department of Urology, RWTH University, Pauwelsstrasse 30, 52074 Aachen, Germany. Tel. +49 241 8037317; Fax: +49 241 8082317. E-mail address: [email protected] (T.H. Kuru).

http://dx.doi.org/10.1016/j.euf.2015.06.003 2405-4569/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

118

1.

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

Introduction

Since the introduction of prostate-specific antigen (PSA) testing into clinical routine, the incidence of prostate cancer (PCa) has increased, but the decline in PCa mortality is debatable [1]. According to the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with 13-yr follow-up, 781 men must be invited for PSA testing to prevent one death from PCa [1]. In addition, the clinical diagnostic tools available, such as PSA testing and digital rectal examination (DRE), have high uncertainty for PCa detection and grading. To date, the standard modality for PCa detection is a 10–12-core transrectal ultrasound (TRUS)-guided biopsy [2]. This biopsy technique has several limitations. In particular, PCa in the anterior and/or apical parts of the gland is likely to be undersampled via a transrectal approach [3,4]. This review provides an overview of the imaging modalities available for PCa detection and a critical analysis of their clinical benefits. 2.

Evidence acquisition

2.1.

Study selection

We performed a comprehensive search of the PubMed database from August 2004 to August 2014. Earlier publications were included if they reported the principle or the first clinical results for a particular technique. 2.2.

Inclusion criteria

We included original articles in the English language that contributed to a nonsystematic overview of PCa diagnostic techniques. Each section was written by one expert author in that specific field. Every author selected the literature articles independently. For each diagnostic tool, a separate search (‘‘diagnostic tool’’ AND prostate cancer) was performed. After review of the title and abstract regarding eligibility, publications with a higher impact factor were given priority if similar methods were described. 3.

Evidence synthesis

3.1.

Diagnostic tools

3.1.1.

Conventional (grayscale) TRUS

One of the first articles on TRUS-guided biopsy (Fig. 1) was by Holm and Gammelgaard [5]. This was seen as a dramatic improvement over the commonly performed finger-guided prostate biopsy first described by Astraldi [6]. The main advantage of TRUS in detection of PCa foci is the visualization of hypoechogenic lesions in the gland. The advantage of guided biopsies for such lesions has been demonstrated in several studies [7,8]. The main limitation of TRUS in the detection of PCa lesions lies in differences in appearance. Some PCa lesions may appear isoechogenic or sometimes hyperechogenic, resulting in wide ranges for sensitivity (18–96%) and specificity (46–91%) [9,10]. In a

Fig. 1 – Transrectal ultrasound (B mode) showing the prostate gland in a 56-yr-old man. From Mitterberger et al. [12].

prospective analysis, Taverna et al. [11] observed a detection rate of 29% for 13-core TRUS-guided biopsy in a subcohort of 100 patients. This low detection rate was confirmed by Mitterberger et al. [12] in a retrospective cohort of 1776 men (Table 1). A new method for analyzing grayscale TRUS images is computerized (C)-TRUS [13]. This technique analyzes TRUS images either on site (stand-alone device) or via the Internet. These analyses provides results in which tumor-suspicious areas are marked in the original static images. In conclusion, grayscale TRUS alone is not suitable for visualizing PCa lesions. Nevertheless, it is a useful tool for other indications (anatomic visualization, volume measurement) in urologic practice. Computerized image analysis techniques are under investigation (C-TRUS). However, standard grayscale TRUS is still the standard technique for biopsy guidance according to European Association of Urology (EAU) guidelines [2]. 3.1.2.

Contrast-enhanced (CE)-TRUS

Enhancement of a TRUS signal using air bubbles (Fig. 2) was first described in 1968 [14]. The bubbles are injected intravenously and remain inside blood vessels, including microvessels. Different agents with several shells for stabilization have been investigated. Clinically, CE ultrasound is now mainly used in other medical specialties, such as for cardiac perfusion measurements and detection of liver malignancies [15,16]. In PCa detection, CE-TRUS shows increased tumor vascularity for different grades [17]. Several studies on this topic have been published (Table 2). In a prospective randomized trial, Mitterberger et al. [18] compared CE-TRUS-targeted five-core biopsy to ten-core TRUS random biopsy in patients without a previous cancer diagnosis. Despite using only half the number of biopsy cores, the detection rate per core was significantly higher in the CE-TRUS group (15.6% vs 6.8%, p < 0.001). In contrast, Taverna et al. [11] found no difference in detection rates among CE-TRUS, Doppler sonography, and 13-core random

119

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

Table 1 – Studies on conventional grayscale TRUS with a very low rate of PCa detection Study

Patients (n)

Taverna et al. [11] Brock et al. [9] Mitterberger et al. [12] Grabski et al. [13]

Comparator

TRUS only

Biopsy-naive

100 229 1776 75

NR 0 905 75

13-core TR biopsy/Doppler TRUS RP specimen 12-core TRUS biopsy 12-core TRUS biopsy

PCa diagnosed,

Sensitivity

Specificity

n/N (%)

(%)

(%)

29/100 (29) 215/894 (24) a 410/1776 (23) 31/75 (41)

NR 18 NR NR

NR 91 NR NR

TRUS = transrectal ultrasound; PCa = prostate cancer; NR = not reported; TR = transrectal; RP = radical prostatectomy. Reported as the detection rate per lesion.

a

Table 2 – Studies on CE-TRUS showing wide ranges for detection, sensitivity, and specificity rates among centers Study

Patients (n) Total

Zhao et al. [19] Halpern et al. [23] Aigner et al. [24] Taverna et al. [11] Seitz et al. [21] Zhao et al. [25] Mitterberger et al. [12] Mitterberger et al. [18] Cornelis et al. [20]

Comparator

PCa diagnosed,

Biopsy-naive

65 272 133 300

NR NR 72 NR

35

NR

Positive cores (%)

n/N (%)

Targeted

29/65 (44.6) 118/272 (43) 79/133 (59.4) 88/300 (29.3)

33/44 (75) 203/1237 (16.4) 97/131 (74) a NR

–

Comparator

CE-TRUS

162/336 (48.2) 276/3264 (8.5) 97/164 (59.1) a NR

65.5/69.4 NR NR 23/68

79.3/86.1 NR NR 54/42

–

–

42/75

71/50

43/106 (40.6) 559/1776 (31)

– 961/8880 (10.8)

– 910/1 7760 (5.1)

– NR

65/95 NR

34/500 (6.8)

NR

NR

NR

90/12.6

NR 905

12-core systematic TRUS 12-core systematic TRUS RTE-targeted biopsy 13-core TR biopsy/ Doppler TRUS B-mode TRUS (RP specimen) 12-core TRUS biopsy 12-core TRUS biopsy

100

NR

10-core TRUS biopsy

29/100 (29)

39/250 (15.6)

178

0

12-core TRUS biopsy

83/178 (46.6)

18/158 (11.3)

106 1776

Sensitivity/specificity (%)

Comparator

b

23/158 (14.5)

b

CE = contrast-enhanced; TREUS = transrectal ultrasound; PCa = prostate cancer; RTE = real-time elastography; NR = not reported; TR = transrectal; RP = radical prostatectomy. a Reported as the detection rate per lesion. b Reported as the detection rate per patient.

biopsy in a prospective randomized trial in patients without a previous cancer diagnosis. The sensitivity and specificity of CE-TRUS were 54–79.3% and 42–86.1%, respectively [11,19]. Cornelis et al. [20] reported detection rates of 24% for targeted biopsies and 30.7% for random biopsies in

Fig. 2 – Contrast-enhanced color Doppler ultrasound image demonstrating enhancement of the prostate in the left mid-gland with suspicion of malignancy. Targeted prostate biopsy of the enhanced area revealed prostate cancer with Gleason score 8. From Mitterberger et al. [12].

patients with a previous negative 12-core TRUS biopsy. One major drawback of CE-TRUS may be the destruction of microbubbles by the Doppler signal. To overcome this issue, cadence-contrast pulse sequence technology is under investigation. In a cohort of 35 patients, Seitz et al. [21] found sensitivity of 71% and specificity of 50% for this technique for PCa detection on a per-patient basis. Jung et al. [22] reported results for quantitative analysis of CE-TRUS in 20 patients. The authors recorded the wash-in rate, mean transit time, and rise time in the prostate and compared these to histopathology after radical prostatectomy (RP). The highest detection rate was obtained for analysis of early contrast enhancement, with sensitivity of 88% and specificity of 100%. Studies in the literature have used different ultrasound techniques, such as Doppler ultrasound and harmonic ultrasound. This could explain the wide range of detection rates. Nevertheless, CE-TRUS yields very inhomogeneous results and might not be the ideal technique for clinical practice, as the results seem to be very user-dependent. In experienced hands, CE-TRUS may be of diagnostic benefit in augmenting grayscale TRUS. 3.1.3.

Real-time elastography (RTE)

Ultrasound-based elastography is an imaging modality that allows visualization of potential cancerous tissue on a video

120

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

Table 3 – Studies on elastography showing promising sensitivity and specificity results in patients before radical prostatectomy Study

Walz et al. [35] Salomon et al. [36] Pallwein et al. [37] a Rausch et al. [38] Tsutsumi et al. [39] Brock et al. [40]

Patients (n)

Sensitivity

Specificity

PPV

NPV

Total

Biopsy-naive

(%)

(%)

(%)

(%)

32 109 87 61 55 86

0 0 0 0 0 0

58.5 75.4 92.0 53.0 74.8 49.0

43.3 76.6 80.0 74.0 65.0 73.6

54.1 87.8 95.0 78.0 81.1 77.8

NR 59.0 NR 46.0 84.4 50.7

PPV = positive predictive value; NPV = negative predictive value; NR = not reported. Index lesion 5 mm.

a

screen. It can portray differences in tissues density within the prostate in different colors (qualitative; Fig. 3B) and/or in quantitative units (kPa; Fig. 3B) in ultrasound images. The underlying principle is that malignant tissue is harder than normal tissue and therefore differentiation of malignant and benign tissues might be possible. Sensitivity and specificity rates of 53.8–92.0% and 43.3–89.5%, respectively, have been reported for PCa detection. The negative predictive value (NPV) for malignant lesions was up to 84.4% [26]. The technique was first reported in 1991 [27]

and several improvements by different ultrasound companies have led to greater accuracy for PCa detection (Table 3). There are differences in technique for different systems, or the principle of the technique itself (RTE and shear-wave elastography). One of the greatest benefits of ultrasoundbased elastography compared to other imaging techniques is that suspicious areas can be targeted in real time in the elastography mode while performing TRUS. 3.1.3.1. Elastography before systematic biopsy. The Martini Clinic (Hamburg, Germany) reported an increase in detection rate of 7.1% when adding four elastography-targeted biopsy cores to a ten-core random biopsy examination among 1024 patients [28]. The increment in detection rate (up to 24.8%) was best for patients with a previous negative biopsy. Aigner et al. [29] reported sensitivity of 74.0%, specificity of 60.0%, a positive predictive value (PPV) of 39.0%, and NPV of 93.0% for RTE-targeted biopsies; the percore detection rate was 4.7-fold higher than for systematic biopsies. 3.1.3.2. Comparison to mpMRI. Three studies reported better [30] or comparable [24,31] PCa detection rates for RTE in comparison to mpMRI at 1.5 T. Pelzer et al. [32] described comparable results for RTE and 3-T mpMRI. Whereas MRI had better detection rates in the apical and middle parts of the prostate, RTE had a superior detection rate for the base and apex. Therefore, a combination of both modalities might increase the overall detection rate. Brock et al. [33] performed a prospective analysis using mpMRI and elastography in patients with proven PCa before RP. The area under the curve (AUC) of 0.65 for mpMRI was meaningfully enhanced to 0.75 using MRI-RTE fusion [33]. Further studies are required to confirm these data and the practicality of the approach in clinical routine.

Fig. 3 – (A) Real-time elastography in a phantom model. Left, elastogram; right, conventional transrectal ultrasound. Hard tissue is displayed in blue. A real-time targeted biopsy can be performed. (B) Shear-wave elastography with qualitative (hard tissue is red) and quantitative measurement (kPa).

3.1.3.3. Shear-wave elastography. Shear-wave elastography offers the possibility to use values as cutoffs for benign or malignant tissue. Boehm et al. [34] found significant differences in shear-wave elasticity between benign tissue (42 kPa, range 29–71.3) and PCa nodules (88 kPa, range 54–123; p < 0.001). Incorporation of quantitative cutoff points could improve the accuracy and usability of elastography, but this has yet to be shown. Despite the benefits of elastography, there are some limitations when differentiating PCa foci from chronic

121

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

3.1.4.

HistoScanning

HistoScanning (Fig. 4) is an ultrasound-based imaging technique for detection and localization of PCa [41] consisting of three steps. First, motorized TRUS generates a complete scan of the prostate. Second, the examiner defines the region of interest using the HistoScanning software. Finally, computerized HistoScanning analyses provide color-coded areas suspicious for PCa and the corresponding tumor volume in a non–real-time manner.

Fig. 4 – An example of one sector of the ultrasound volume file in which the red area corresponds to the malignant scores for the histograms. From Braeckman et al. [41].

prostatitis or calcification. A systematic biopsy cannot be omitted according to unpublished data recorded by the Martini Clinic, since approximately 20% of cases with a negative elastogram harbor cancerous tissue (most of them Gleason score <7) on systematic biopsy. In conclusion, elastography shows promising results according to the literature. Different techniques (eg, shear-wave elastography) may allow the introduction of thresholds for tissue density and are under investigation, but data from large prospective trials are lacking.

3.1.4.1. HistoScanning versus final pathology. A pilot study observed significant correlation (r = 0.95, p < 0.001) between the diameter of the index tumor according to HistoScanning and final pathology in 14 PCa patients scheduled for RP (Table 4) [41]. On the basis of this data set, the same group published a second study [42] and found sensitivity of 100% and specificity of 82% for detection of cancer foci for HistoScanning signal volumes 0.5 ml. Despite these encouraging findings, subsequent studies yielded controversial results. Macek et al. [43] recorded an area under the curve (AUC) of 0.63 when using HistoScanning for detection of cancer foci of 0.1 ml, with overall sensitivity of 60% and specificity of 66%. These values improved to 73% and 63% when taking only selected areas of the prostate into account [43]. Several studies investigated the ability of HistoScanning to measure total tumor volume compared to final pathology. Simmons et al. [44] observed favorable correlation (r = 0.7) between tumor volume measured by HistoScanning and final pathology in 27 RP patients. Conversely, in a larger patient cohort (n = 148) Schiffmann et al. [45] found no significant correlation between tumor volume measured by HistoScanning and final pathology (r = –0.008, p = 0.9).

Table 4 – HistoScanning results before radical prostatectomy and in prostate biopsy Study

Study concept

Patients

Correlation Coefficient

Braeckmann et al. [41] Braeckmann et al. [42] Braeckmann et al. [42] Macek et al. [43] Simmons et al. [44] Simmons et al. [44] Schiffmann et al. [45] Schiffmann et al. [45] ˜ ez-Mora et al. [46] Nu´n Javed et al. [47] Javed et al. [47] Schiffmann et al. [48]

Diameter of index tumor: HS vs FP at RP Total tumor volume: HS vs FP at RP Cancer foci 0.5 ml Cancer foci 0.2 ml Total tumor volume: HS vs FP at RP Cancer foci 0.5 ml Total tumor volume: HS vs FP at RP Total tumor volume: HS vs FP at RP HS at biopsy HS at biopsy HS at biopsy HS at biopsy >0 ml b >0.2 ml b >0.5 ml b

AUC

p value

Sensitivity

Specificity

PPV

NPV

(%)

(%)

(%)

(%)

14

0.95

<0.001

NA

NA

NA

NA

NA

13

0.98

<0.001

NA

NA

NA

NA

NA

13 98 27

NA NA 0.7

NA 0.63 NA

100 60 NA

81 66 NA

80 NA NA

100 NA NA

23 (138 sextants) 148 36

a

32 57 24 (144 sextants) 198 (1188 sextants)

NA –0.008

0.9

NA NA

90 NA

70 NA

80 NA

84 NA

0.004

0.8

NA

NA

NA

NA

NA

NA NA NA 0.58

94 100 100

80 19 5.9

68 60 NA

97 100 NA

84 61 40

28 51 73

30 29 33

83 80 79

NA NA NA NA

AUC = area under the curve; PPV = positive predictive value; NPV = negative predictive value; HS = HistoScanning; FP = final pathology; RP = radical prostatectomy; r: correlation coefficient; NA = not applicable. a Subgroup analyses for patients with D’Amico high-risk prostate cancer. b HistoScanning signal volume cutoff for prediction of a positive biopsy.

122

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

Moreover, the correlation did not improve after adjustment for D’Amico risk, prostate volume, experience of HistoScanning examiner, distance from the ultrasound probe to the prostate, or the quality of the initial HistoScanning data (all p > 0.05) [45]. 3.1.4.2. HistoScanning at prostate biopsy. Different studies investigated the performance of HistoScanning at prostate ˜ ez-Mora et al. [46] biopsy. In a series of 32 patients, Nu´n observed sensitivity of 94%, specificity of 80%, PPV of 68%, and NPV of 97% for HistoScanning before prostate biopsy. Besides the small sample size, the study was limited by the inclusion of patients who already had a PCa diagnosis before biopsy (31%) [46]. Moreover, HistoScanning signals were rated positive for prostatic intraepithelial neoplasia, even though it is not PCa. In a series of 57 patients who underwent perineal prostate biopsy, Javed et al. [47] found a lower detection rate for HistoScanning (13%) than for the standard template (54%); HistoScanning had sensitivity of 100% and specificity of 19%. Similarly, in a study of 1188 sextants in 198 men, Schiffmann et al. [48] found sensitivity of 84% and specificity of 28% for HistoScanning when compared to biopsy results. These values did not improve sufficiently for HistoScanning signal volume cutoffs of >0.2 ml (61% and 51%) and >0.5 ml (40% and 73%) [48]. Few studies have addressed the ability of HistoScanning to detect PCa. Moreover, studies have focused on different endpoints and have reported controversial results. All biopsy studies were limited by the inability to perform real-time targeted biopsies using HistoScanning. The first encouraging biopsy data [46] included just 32 patients. Subsequent analyses for larger patient cohorts were not able to confirm these observations [47,48]. It should be noted that targeted biopsies using fusion of HistoScanning and conventional ultrasound are currently available. The first data for this innovative technique are still awaited. In conclusion, it is debatable whether HistoScanning can improve PCa detection. 3.1.5.

MRI and MRI-TRUS fusion biopsy

Owing to its high soft-tissue contrast, high resolution, and ability to simultaneously image functional parameters, MRI provides accurate visualization of the prostate gland. Anatomic T2-weighted MRI is the cornerstone of prostate MRI examination. Functional imaging techniques are often performed to enhance the specificity, including diffusionweighted MRI (DWI), dynamic CE-MRI (DCE-MRI), and three-dimensional MR spectroscopy imaging [49–55]. mpMRI plays an important role in PCa detection, localization, and staging; in image-guided targeted prostate biopsy; and in assessing PCa changes after treatment [56,57]. According to recent guidelines, a field of 1.5 T or 3 T can be used for prostate MRI if the acquisition parameters are optimized for appropriate contemporary technology. Prostate mpMRI at lower magnetic field strength (<1.5 T) is not recommended. 3.1.5.1. MRI techniques. T1-weighted MRI has a limited role in PCa detection. This sequence is mainly used to detect biopsy

hemorrhage or artifacts, which can be a confounding factor in anatomic T2-weighted MR images [58]. Anatomic T2-weighted MRI is the most widely used sequence for prostate MRI and is helpful for zonal delineation and tumor detection. T2-weighted MR images can clearly differentiate the normal intermediate to high signal intensity for the peripheral zone from the low signal intensity for the central and transition zones [59]. On T2weighted images, PCa may appear as an area of low signal intensity within the high signal intensity of a normal peripheral zone. DWI can quantify the random motion of water molecules in an indirect manner (Brownian effect) [60]. This impedance of the diffusion of water molecules can be quantitatively assessed using the apparent diffusion coefficient (ADC). PCa tissue has a higher cellular density than healthy peripheral-zone prostate tissue. Therefore, in ADC maps PCa often shows lower ADCs in comparison to surrounding healthy peripheral-zone prostate tissue [61,62]. DCE-MRI following administration of low–molecularweight contrast medium is the most common imaging method for evaluating human tumor vascular function in situ. PCa tends to enhance earlier, faster, and to a greater extent and shows earlier contrast agent washout in comparison to healthy prostate tissue [63,64]. For result standardization and better comparability, the European Society of Urogenital Radiology introduced the Prostate Imaging and Reporting and Data System (PI-RADS) in 2012 [65]. Some studies have investigated the use of mpMRI before RP. Le et al. [66] reported on 122 men who underwent mpMRI before RP. The overall sensitivity of mpMRI in detecting PCa foci was only 47% (132/283), but this increased to 80% for index tumors and 72% (102/141) for tumors >1 cm. The detection sensitivity for PCa of Gleason 7 was 72% (96/134). Therefore, the main limitation of mpMRI seems to be the detection of small and low-grade PCas. These results were confirmed by other groups [67]. The logical consequence of improved visualization of tumor foci by mpMRI and the limited MRI scanning time in most institutions is the integration of this information into TRUS. Several systems with either a transrectal or a transperineal approach are commercially available (Koelis, Biopsee, and UroNav, among others). MRI-TRUS fusion (Fig. 5) can also be performed by cognitive fusion on the basis of zonal anatomy or imaging landmarks. Puech et al. [68] performed a randomized trial in which cognitive fusion showed similar detection rates to software fusion. Baco et al. [69] performed MRI-TRUS fusion biopsy before RP and were able to detect 95% of index lesions (the largest tumor in 98% of cases). The MRI-TRUS fusion technique has been validated in active surveillance patients. Da Rosa et al. [70] performed fusion and standard biopsies in 72 patients under active surveillance, finding Gleason 7 cancer in 26% of patients. Seven patients were diagnosed via targeted biopsies (UroNav system) alone. The rate of significant PCa detection was sixfold higher for targeted cores than for systematic TRUS-guided biopsies. Radtke et al. [67] reported a

123

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

techniques lies in the deformation of the gland and matching problems between mpMRI and fusion biopsy intervention. Several groups are working on this issue [76] by validating deformation algorithms, especially for focal treatment. In conclusion, mpMRI and MRI-TRUS fusion biopsy seem to be valuable tools for enhancing PCa diagnostics, especially in patients undergoing rebiopsy or under active surveillance (Table 5). 3.2.

Fig. 5 – Sagittal transrectal ultrasound (TRUS) on magnetic resonance imaging (MRI)/TRUS fusion biopsy via a perineal approach. The prostate contour is shown in red, the needle trajectory in green, and the expected biopsy core in yellow.

remarkably high detection rate (46%) for MRI-TRUS fusion biopsies in patients undergoing rebiopsy. Another interesting issue is the potential of MRI-TRUS fusion biopsy to correctly predict Gleason score at final pathology. Le at al [71] used an Artemis system for 54 patients who subsequently underwent RP. The Gleason concordance with RP specimens was 57% for targeted cores and 50% for mapping biopsies. The combination of targeted and systematic cores showed concordance of 72%. Baco et al. [69] reported 69% concordance for the overall Gleason score. The main limitation of fusion techniques is the limited ability of mpMRI to detect small and low-grade PCa. Valerio et al. [72] and Schoots et al. [73] published similar results in the latest reviews of MRI-guided biopsies. To some extent, this limitation can be compensated if additional random cores are taken during biopsy [67,74]. Whether detection of such small and well-differentiated PCa is necessary remains a matter of debate [75]. The second limitation of these

Discussion

The patient cohorts and inclusion criteria in the studies reviewed here are very heterogeneous, so detection rates cannot be compared between publications. The primary endpoints are very different among the papers reviewed, and some secondary endpoints are not reported in all articles. One major limitation in interpretation is that some studies include patients because of suspicion of PCa (elevated PSA and/or suspicious DRE), while others include patients with a confirmed PCa diagnosis. When comparing sensitivity and specificity values reported here, the reader should be aware of the influence of biopsy data on sensitivity and specificity calculations. Both calculations are biased by the sampling error and false negative rate of biopsies. Reports and calculations based on whole-mount sections, which minimize these biases, are rare and not available for every imaging modality. The rate of detection for new imaging modalities is reported on a per-core or perpatient basis, which makes it difficult to compare different studies. We believe that the detection rate per patient is more meaningful for clinical routine, but both detection rates may be reported in larger trials. Despite the recommendation for TRUS-guided biopsy in the latest EAU guideline [2], TRUS alone does not seem to be sufficient for PCa detection because of differences in lesion appearance in grayscale TRUS. This is reflected by the low sensitivity for detection of PCa foci using this technique alone. A prospective randomized control trial (level 1b evidence, Oxford classification) was reported by Taverna et al. [11]. They randomized 300 patients to either standard TRUS or Doppler sonography with and without contrast. There were no significant differences in detection rate among the three groups.

Table 5 – Detection of prostate cancer by mpMRI and mpMRI-TRUS fusion biopsy Study

Le et al. [66] (all tumors) Radtke et al. [67] Turkbey et al. [54] Thompson et al. [77] Isebaert et al. [78] Arumainayagam et al. [79] Tamada et al. [52] Haffner et al. [80]

Patients (n) Total

Biopsy-naive

122 294 70 165 75 64 50 555

0 186 0 0 0 3 50 NR

Gold standard

Whole mount Mapping biopsy Whole mount Mapping biopsy Whole mount Mapping biopsy 12-core biopsy 10–12-core biopsy

PCa diagnosed

Sensitivity

Specificity

PPV

NPV

(%)

(%)

(%)

(%)

(%)

NA 51 NA 61 NA 84 70 54

47 88 42 94 59 64 53 83

NR 55.6 83 50 84 80 93 61

25 67.4 NR 94 72 40 73 NR

75 81.6 NR 52 74 91 85 NR

mpMRI = multiparametric magnetic resonance imaging; TRUS = transrectal ultrasound; PCa = prostate cancer; PPV = positive predictive value; NPV = negative predictive value; NA = not applicable; NR = not reported.

124

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

Therefore, CE-TRUS seems to be very user-dependent, as reflected in wide ranges for detection, sensitivity, and specificity rates. Promising HistoScanning results were first reported in 2008 by Braeckman et al. [41], but further studies were not able to confirm these findings (sensitivity 40/13% and specificity 73/54%) [47,48]. The results published to date leave a large question mark regarding whether this nonreal-time imaging technique can improve PCa detection at the current state. Different elastography techniques (real-time and shearwave elastography) are used to analyze the stiffness of prostate tissue. Despite promising results from different groups [9,28,33,34], there seem to be some limitations in detecting lower-grade PCa with this technique. Consistently high detection rates for significant PCa have been reported by different centers for MRI-TRUS fusion biopsy. The number of biopsies needed to detect relevant PCa seems lower in comparison to standard systematic biopsy. Nevertheless, mpMRI and therefore MRI-TRUS fusion biopsies seem to overlook small cancer foci, even for those of high Gleason score [66]. In addition, MRI-TRUS fusion biopsies have limitations in predicting Gleason score concordance with RP specimens. In comparison to the other techniques reviewed, the use of mpMRI and its fusion with standard TRUS probably provides the best results in clinical practice at present. The combination of targeted and systematic cores seems to yield the greatest accuracy and may be considered if an exact Gleason score is likely to change treatment planning.

Supervision: Rastinehad. Other: None. Financial disclosures: Timur H. Kuru certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Ardeshir R. Rastinehad has research agreements with Invivo and Philips Healthcare. The other authors have nothing to disclose. Funding/Support and role of the sponsor: None.

References [1] Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014;384:2–27. [2] Heidenreich A, Abrahamsson P-A, Artibani W, et al. Early detection of prostate cancer: European Association of Urology recommendation. Eur Urol 2013;64:347–54. [3] Nevoux P, Ouzzane A, Ahmed HU, et al. Quantitative tissue analyses of prostate cancer foci in an unselected cystoprostatectomy series. BJU Int 2011;110:517–23. [4] Mygatt J, Sesterhenn I, Rosner I, et al. Anterior tumors of the prostate: clinicopathological features and outcomes. Prostate Cancer Prostatic Dis 2014;17:75–80. [5] Holm HH, Gammelgaard J. Ultrasonically guided precise needle placement in the prostate and the seminal vesicles. J Urol 1981;125:385–7. [6] Astraldi A. Diagnosis of cancer of the prostate: biopsy by rectal route. Urol Cutan Rev 1937;41:421. [7] Lee HY, Lee HJ, Byun S-S, Lee SE, Hong SK, Kim SH. Classification of focal

4.

Conclusions

prostatic lesions on transrectal ultrasound (TRUS) and the accuracy of TRUS to diagnose prostate cancer. Korean J Radiol 2009;10:244–51.

Standard grayscale TRUS seems to be unreliable for PCa detection. Among the techniques reviewed, elastography, mpMRI, and MRI-TRUS fusion biopsy seem to be suitable for enhancing PCa diagnosis. MRI-TRUS fusion seems to be the technique with the greatest integration in clinical routine and provides reproducible results in urology practice. Elastrography shows promising results according to the literature. CE-TRUS shows very inhomogeneous results and might not be the ideal technique for clinical practice. The value of HistoScanning must be questioned according to the literature.

[8] Tamsel S, Killi R, Hekimgil M, Altay B, Soydan S, Demirpolat G. Transrectal ultrasound in detecting prostate cancer compared with serum total prostate-specific antigen levels. J Med Imaging Radiat Oncol 2008;52:24–8. [9] Brock M, von Bodman C, Sommerer F, et al. Comparison of real-time elastography with grey-scale ultrasonography for detection of organ-confined prostate cancer and extra capsular extension: a prospective analysis using whole mount sections after radical prostatectomy. BJU Int 2011;108:E217–22. [10] Lee F, Siders DB, Torp-Pedersen ST, Kirscht JL, McHugh TA, Mitchell AE. Prostate cancer: transrectal ultrasound and pathology comparison. A preliminary study of outer gland (peripheral and central zones) and inner gland (transition zone) cancer. Cancer 1991;67:1132–42. [11] Taverna G, Morandi G, Seveso M, et al. Colour Doppler and micro-

Author contributions: Timur H. Kuru had full access to all the data in the

bubble contrast agent ultrasonography do not improve cancer

study and takes responsibility for the integrity of the data and the

detection rate in transrectal systematic prostate biopsy sampling.

accuracy of the data analysis.

BJU Int 2011;108:1723–7. [12] Mitterberger MJ, Aigner F, Horninger W, et al. Comparative effi-

Study concept and design: The editors of European Urology Focus.

ciency of contrast-enhanced colour Doppler ultrasound targeted

Acquisition of data: Kuru, Fu¨tterer, Schiffmann, Porres.

versus systematic biopsy for prostate cancer detection. Eur Radiol

Analysis and interpretation of data: Kuru, Fu¨tterer, Schiffmann, Porres.

2010;20:2791–6.

Drafting of the manuscript: Kuru, Fu¨tterer, Schiffmann, Porres. Critical revision of the manuscript for important intellectual content: Kuru,

[13] Grabski B, Baeurle L, Loch A, Wefer B, Paul U, Loch T. Computerized transrectal ultrasound of the prostate in a multicenter setup (C-

Fu¨tterer, Schiffmann, Porres, Salomon, Rastinehad.

TRUS-MS): detection of cancer after multiple negative systematic

Statistical analysis: None.

random and in primary biopsies. World J Urol 2011;29:573–9.

Obtaining funding: None. Administrative, technical, or material support: None.

[14] Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol 1968;3:356–66.

125

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

[15] Kim TK, Lee KH, Khalili K, Jang H-J. Hepatocellular nodules in liver

[33] Brock M, Roghmann F, Sonntag C, et al. Fusion of magnetic reso-

cirrhosis: contrast-enhanced ultrasound. Abdom Imaging 2011;36:

nance imaging and real-time elastography to visualize prostate

244–63. [16] Quaia E. Assessment of tissue perfusion by contrast-enhanced ultrasound. Eur Radiol 2011;21:604–15.

cancer: a prospective analysis using whole mount sections after radical prostatectomy. Ultraschall Med. In press. http://dx.doi.org/ 10.1055/s-0034-1366563

[17] Frauscher F, Klauser A, Halpern EJ, Horninger W, Bartsch G. Detec-

[34] Boehm K, Salomon G, Beyer B, et al. Shear wave elastography for

tion of prostate cancer with a microbubble ultrasound contrast

localization of prostate cancer lesions and assessment of elasticity

agent. Lancet 2001;357:1849–50. [18] Mitterberger M, Horninger W, Pelzer A, et al. A prospective randomized trial comparing contrast-enhanced targeted versus sys-

thresholds: implications for targeted biopsies and active surveillance protocols. J Urol 2015;193:794–800. [35] Walz J, Marcy M, Pianna JT, et al. Identification of the prostate

tematic ultrasound guided biopsies: Impact on prostate cancer

cancer index lesion by real-time elastography: considerations for

detection. Prostate 2007;67:1537–42.

focal therapy of prostate cancer. World J Urol 2011;29:589–94.

[19] Zhao H-X, Xia C-X, Yin H-X, Guo N, Zhu Q. The value and limitations

[36] Salomon G, Ko¨llerman J, Thederan I, et al. Evaluation of prostate

of contrast-enhanced transrectal ultrasonography for the detection

cancer detection with ultrasound real-time elastography: a com-

of prostate cancer. Eur J Radiol 2013;82:e641–7.

parison with step section pathological analysis after radical pros-

[20] Cornelis F, Rigou G, Le Bras Y, et al. Real-time contrast-enhanced

tatectomy. Eur Urol 2008;54:1354–62.

transrectal US-guided prostate biopsy: diagnostic accuracy in men

[37] Pallwein L, Mitterberger M, Struve P, et al. Real-time elastography

with previously negative biopsy results and positive MR imaging

for detecting prostate cancer: preliminary experience. BJU Int

findings. Radiology 2013;269:159–66. [21] Seitz M, Gratzke C, Schlenker B, et al. Contrast-enhanced transrectal

2007;100:42–6. [38] Rausch S, Alt W, Arps H, Alt B, Ka¨lble T. The utility of transrectal

ultrasound (CE-TRUS) with cadence-contrast pulse sequence (CPS)

sonoelastography in preoperative prostate cancer assessment. Med

technology for the identification of prostate cancer. Urol Oncol

Ultrason 2012;14:182–6.

2011;29:295–301. [22] Jung EM, Wiggermann P, Greis C, et al. First results of endocavity

[39] Tsutsumi M, Miyagawa T, Matsumura T, et al. Real-time balloon inflation elastography for prostate cancer detection and initial

evaluation of the microvascularization of malignant prostate tumors

evaluation

using contrast enhanced ultrasound (CEUS) including perfusion

2010;194:W471–6.

analysis: first results. Clin Hemorheol Microcirc 2012;52:167–77. [23] Halpern EJ, Gomella LG, Forsberg F, McCue PA, Trabulsi EJ. Contrast

of

clinicopathologic

analysis.

Am

J

Roentgenol

[40] Brock M, Eggert T, Palisaar RJ, et al. Multiparametric ultrasound of the prostate: adding contrast enhanced ultrasound to real-time

enhanced transrectal ultrasound for the detection of prostate can-

elastography to detect histopathologically confirmed cancer. J Urol

cer: a randomized, double-blind trial of dutasteride pretreatment. J

2013;189:93–8.

Urol 2012;188:1739–45. [24] Aigner F, Scha¨fer G, Steiner E, et al. Value of enhanced transrectal ultrasound targeted biopsy for prostate cancer diagnosis: a retrospective data analysis. World J Urol 2012;30:341–6. [25] Zhao HW, Luo JH, Xu HX, et al. The value of contrast-enhanced

[41] Braeckman J, Autier P, Garbar C, et al. Computer-aided ultrasonography (HistoScanning): a novel technology for locating and characterizing prostate cancer. BJU Int 2008;101:293–8. [42] Braeckman J, Autier P, Soviany C, et al. The accuracy of transrectal ultrasonography supplemented with computer-aided ultrasonog-

transrectal ultrasound in predicting the nature of prostate diseases

raphy for detecting small prostate cancers. BJU Int 2008;102:

and the Gleason score of prostate cancer by a subjective blood flow

1560–5.

grading scale. Urol Int 2011;87:165–70.

[43] Macek P, Barret E, Sanchez-Salas R, et al. Prostate histoscanning in

[26] Salomon G, Schiffmann J. Real-time elastography for the detection

clinically localized biopsy proven prostate cancer: an accuracy

of prostate cancer. Curr Urol Rep 2014;15:392. [27] Ophir J, Ce´spedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: a

study. J Endourol 2014;28:371–6. [44] Simmons LAM, Autier P, Za´t’ura F, et al. Detection, localisation and

quantitative method for imaging the elasticity of biological tissues.

characterisation of prostate cancer by prostate HistoScanning. BJU

Ultrason Imaging 1991;13:111–34.

Int 2011;110:28–35.

[28] Salomon G, Drews N, Autier P, et al. Incremental detection rate of

[45] Schiffmann J, Fischer J, Tennstedt P, et al. Comparison of prostate

prostate cancer by real-time elastography targeted biopsies in

cancer volume measured by HistoScanning and final histopatho-

combination with a conventional 10-core biopsy in 1024 consecu-

logical results. World J Urol 2014;32:939–44. ˜ ez-Mora C, Garcı´a-Mediero JM, Patin˜o P, et al. Utility of His[46] Nu´n

tive patients. BJU Int 2014;113:548–53. [29] Aigner F, Pallwein L, Junker D, et al. Value of real-time elastography targeted biopsy for prostate cancer detection in men with prostate specific antigen 1.25 ng/ml or greater and 4.00 ng/ml or less. J Urol 2010;184:913–7.

toScanning prior to prostate biopsy for the diagnosis of prostate adenocarcinoma. Actas Urol Esp 2013;37:342–6. [47] Javed S, Chadwick E, Edwards AA, et al. Does prostate HistoScanning play a role in detecting prostate cancer in routine clinical practice?

[30] Sumura M, Shigeno K, Hyuga T, Yoneda T, Shiina H, Igawa M. Initial

Results from three independent studies. BJU Int 2014;114:541–8.

evaluation of prostate cancer with real-time elastography based on

[48] Schiffmann J, Tennstedt P, Fischer J, et al. Does HistoScanningTM

step-section pathologic analysis after radical prostatectomy: a

predict positive results in prostate biopsy? A retrospective analysis

preliminary study. Int J Urol 2007;14:811–6.

of 1,188 sextants of the prostate. World J Urol 2014;32:925–30.

[31] Aigner F, Pallwein L, Schocke M, et al. Comparison of real-time

[49] Pinto PA, Chung PH, Rastinehad AR, et al. Magnetic resonance

sonoelastography with T2-weighted endorectal magnetic reso-

imaging/ultrasound fusion guided prostate biopsy improves cancer

nance imaging for prostate cancer detection. J Ultrasound Med

detection following transrectal ultrasound biopsy and correlates

2011;30:643–9.

with multiparametric magnetic resonance imaging. J Urol

[32] Pelzer AE, Heinzelbecker J, Weiss C, et al. Real-time sonoelastography compared to magnetic resonance imaging using four dif-

2011;186:1281–5. [50] Sciarra A, Panebianco V, Salciccia S, et al. Modern role of magnetic

ferent modalities at 3.0 T in the detection of prostate cancer:

resonance and spectroscopy in the imaging of prostate cancer. Urol

strength and weaknesses. Eur J Radiol 2013;82:814–21.

Oncol 2011;29:12–20.

126

EUROPEAN UROLOGY FOCUS 1 (2015) 117–126

[51] Puech P, Sufana Iancu A, Renard B, Villers A, Lemaitre L. Detecting

[67] Radtke JP, Kuru TH, Boxler S, et al. Comparative analysis of trans-

prostate cancer with MRI—why and how. Diagn Interv Imaging

perineal template saturation prostate biopsy versus magnetic res-

2012;93:268–78.

onance imaging targeted biopsy with magnetic resonance imaging-

[52] Tamada T, Sone T, Higashi H, et al. Prostate cancer detection in patients with total serum prostate-specific antigen levels of 4-10

ultrasound fusion guidance. J Urol 2015;193:87–94. [68] Puech P, Rouviere O, Renard-Penna R, et al. Prostate cancer diag-

ng/mL: diagnostic efficacy of diffusion-weighted imaging, dynamic

nosis: multiparametric MR-targeted biopsy with cognitive and

contrast-enhanced MRI, and T2-weighted imaging. Am J Roent-

transrectal US-MR fusion guidance versus systematic biopsy—pro-

genol 2011;197:664–70. [53] Hoeks CMA, Barentsz JO, Hambrock T, et al. Prostate cancer: multi-

spective multicenter study. Radiology 2013;268:461–9. [69] Baco E, Ukimura O, Rud E, et al. Magnetic resonance imaging-

parametric MR imaging for detection, localization, and staging.

transectal ultrasound image-fusion biopsies accurately character-

Radiology 2011;261:46–66.

ize the index tumor: correlation with step-sectioned radical pros-

[54] Turkbey B, Pinto PA, Mani H, et al. Prostate cancer: value of multiparametric mr imaging at 3 t for detection—histopathologifc correlation 1. Radiology 2010;255:89–99. [55] Delongchamps NB, Rouanne M, Flam T, et al. Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2-weighted, dynamic contrastenhanced and diffusion-weighted imaging. BJU Int 2011;107: 1411–8.

tatectomy specimens in 135 patients. Eur Urol 2015;67:787–94. [70] Da Rosa MR, Milot L, Sugar L, et al. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging 2015;41:220–5. [71] Le JD, Stephenson S, Brugger M, et al. MRI-ultrasound fusion biopsy for prediction of final prostate pathology. J Urol 2014;192:1367–73. [72] Valerio M, Donaldson I, Emberton M, et al. Detection of clinically

[56] Delongchamps NB, Beuvon F, Eiss D, et al. Multiparametric MRI is

significant prostate cancer using magnetic resonance imaging–

helpful to predict tumor focality, stage, and size in patients diag-

ultrasound fusion targeted biopsy: a systematic review. Eur Urol.

nosed with unilateral low-risk prostate cancer. Prostate Cancer Prostatic Dis 2011;14:232–7. [57] Scheenen TWJ, Fu¨tterer J, Weiland E, et al. Discriminating cancer

In press. http://dx.doi.org/10.1016/j.eururo.2014.10.026 [73] Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MGM. Magnetic resonance imaging–targeted biopsy may

from noncancer tissue in the prostate by 3-dimensional proton

enhance the diagnostic accuracy of significant prostate cancer

magnetic resonance spectroscopic imaging: a prospective multi-

detection compared to standard transrectal ultrasound-guided

center validation study. Invest Radiol 2011;46:25–33.

biopsy: a systematic review and meta-analysis. Eur Urol. In press.

[58] White S, Hricak H, Forstner R, et al. Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images. Radiology 1995;195:385–90. [59] Hricak H, Williams RD, Spring DB, et al. Anatomy and pathology of the male pelvis by magnetic resonance imaging. Am J Roentgenol 1983;141:1101–10. [60] Stejskal E, Tanner J. Spin diffusion measurements: spin echoes in

http://dx.doi.org/10.1016/j.eururo.2014.11.037 [74] Kuru TH, Roethke MC, Seidenader J, et al. Critical evaluation of magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy for detection of prostate cancer. J Urol 2013;190:1380–6. [75] Rais-Bahrami S, Tu¨rkbey B, Rastinehad AR, et al. Natural history of small index lesions suspicious for prostate cancer on multipara-

the presence of a time-dependent field gradient. J Chem Phys

metric MRI: recommendations for interval imaging follow-up.

1965:42. http://dx.doi.org/10.1063/1.1695690.

Diagn Interv Radiol 2014;20:293–8.

[61] Kim CK, Park BK, Lee HM, Kwon GY. Value of diffusion-weighted

[76] Dickinson L, Hu Y, Ahmed HU, et al. Image-directed, tissue-pre-

imaging for the prediction of prostate cancer location at 3T using a

serving focal therapy of prostate cancer: a feasibility study of a

phased-array coil: preliminary results. Invest Radiol 2007;42:842–7.

novel deformable magnetic resonance-ultrasound (MR-US) regis-

[62] Tamada T, Sone T, Toshimitsu S, et al. Age-related and zonal anatomical changes of apparent diffusion coefficient values in

tration system. BJU Int 2013;112:594–601. [77] Thompson JE, Moses D, Shnier R, et al. Multiparametric magnetic

normal human prostatic tissues. J Magn Reson Imaging 2008;27:

resonance imaging guided diagnostic biopsy detects significant

552–6.

prostate cancer and could reduce unnecessary biopsies and over

[63] Alonzi R, Padhani AR, Allen C. Dynamic contrast enhanced MRI in prostate cancer. Eur J Radiol 2007;63:335–50. [64] Barentsz JO, Engelbrecht M, Jager GJ, et al. Fast dynamic gadolinium-enhanced MR imaging of urinary bladder and prostate cancer. J Magn Reson Imaging 1999;10:295–304.

detection: a prospective study. J Urol 2014;192:67–74. [78] Isebaert S, Van den Bergh L, Haustermans K, et al. Multiparametric MRI for prostate cancer localization in correlation to whole-mount histopathology. J Magn Reson Imaging 2012;37:1392–401. [79] Arumainayagam N, Ahmed HU, Moore CM, et al. Multiparametric

[65] American College of Radiology. PI-RADS v2. Prostate imaging

MR imaging for detection of clinically significant prostate cancer: a

reporting and data system version 2.0; 2014. http://www.acr.

validation cohort study with transperineal template prostate

org//media/ACR/Documents/PDF/QualitySafety/Resources/ PIRADS/PIRADS%20V2 [66] Le JD, Tan N, Shkolyar E, et al. Multifocality and prostate cancer

mapping as the reference standard. Radiology 2013;268:761–9. [80] Haffner J, Lemaitre L, Puech P, et al. Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance

detection by multiparametric magnetic resonance imaging: correla-

imaging-targeted and systematic biopsy for significant prostate

tion with whole-mount histopathology. Eur Urol 2015;67:569–76.

cancer detection. BJU Int 2011;108:E171–8.