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WFUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography: Part 5. Prostate

      Abstract

      The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced guidelines for the use of elastography techniques, including basic science, breast, liver and thyroid elastography. Here we present elastography in prostate diseases. For each available technique, procedure, reproducibility, results and limitations are analyzed and recommendations are given. Finally, recommendations are given based on the level of evidence of the published literature and on the WFUMB expert group's consensus. This document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of prostate diseases.

      Key Words

      Introduction

      Prostate cancer (PCA) has the highest incidence rate and is the second highest cause of cancer death in men in Western countries. It is the second most frequent malignant tumor in males worldwide (
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      ). With improvements in prostate-specific antigen (PSA) screening, diagnostic techniques and prolonged life expectancy, the incidence and prevalence of PCA have increased steadily in the last decade (
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      ,
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      ). It is reported that more than 500,000 patients per year undergo prostate biopsy in the United States (
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      ). Current guidelines support systematic sampling with 10 to 12 biopsy cores, which has a significantly higher cancer detection rate than sextant biopsies (
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      ). Nevertheless, the conventional biopsy protocol on the one hand misses significant PCA in a large percentage of patients and, on the other hand, detects many insignificant PCAs that do not require immediate treatment, resulting in overdiagnosis and overtreatment (
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      Early detection, PSA screening, and management of over-diagnosis.
      ). The estimated overdetection rate for prostate biopsy ranges from 27% to 56% (
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      Prostate Cancer Imaging Working Group. Challenges in clinical prostate cancer: role of imaging.
      ).
      Methods for detection of PCA include PSA screening, digital rectal examination (DRE) and diagnostic imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI). PCA is generally a stiff lesion compared with normal prostate tissue and can be detected on DRE. However, DRE is subjective and operator dependent, and its sensitivity is questionable for deep or small lesions (
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      ). It has limited accuracy for staging disease and locating the different foci (
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      Characterizing the range of simulated prostate abnormalities palpable by digital rectal examination.
      ), which are two factors mandatory for planning primary therapy. Despite the low specificity of PSA testing and the low sensitivity of systematic biopsy (SB), these techniques remain the standard of care for PCA diagnosis, mainly because of their widespread availability and low cost (
      • Heidenreich A.
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      • Mason M.
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      • Wiegel T.
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      EAU guidelines on prostate cancer: Part I. Screening, diagnosis, and treatment of clinically localised disease.
      ,
      • Mottet N.
      • Bellmunt J.
      • Briers E.
      • van den Bergh R.
      • Bolla M.
      • van Casteren N.
      • Cornford P.
      • Culine S.
      • Joniau S.
      • Lam T.
      • Mason M.
      • Matveev V.
      • van der Poel H.
      • van der Kwast T.
      • Rouvière O.
      • Wiegel T.
      Guidelines on prostate cancer.
      ,
      • Norberg M.
      • Egevad L.
      • Holmberg L.
      • Sparen P.
      • Norlen B.
      • Busch C.
      The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer.
      ,
      • Veiga F.
      • Reixa J.
      • Lopez A.
      • Rosado E.
      • Martin M.
      Current role of PSA and other markers in the diagnosis of prostate cancer.
      ).
      Ultrasound is the most common imaging method for direct visualization of the prostate because it is real time, does not involve ionizing radiation and is low in cost. However, transrectal ultrasound (TRUS) is not highly sensitive or specific (40%–50%) in the diagnosis of PCA because suspicious hypo-echoic areas represent cancer in only 9%–53% of cases with B-mode technique (
      • Beerlage H.
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      • Van D.
      • Kaa C.
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      Correlation of transrectal ultrasound, computer analysis of transrectal ultrasound and histopathology of radical prostatectomy specimen.
      ,
      • Junker D.
      • Schafer G.
      • Kobel C.
      • Kremser C.
      • Bektic J.
      • Jaschke W.
      • Aigner F.
      Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis.
      ,
      • Junker D.
      • Zordo D.
      • Quentin M.
      • Ladurner M.
      • Bektic J.
      • Horniger M.
      • Jaschke W.
      • Aigner F.
      Real-time elastography of the prostate.
      ;
      • Rifkin M.
      • Zerhouni E.
      • Gatsonis C.
      • Quint L.
      • Paushter D.
      • Epstein J.
      • Hamper U.
      • Walsh P.C.
      • McNeil B.J.
      Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer.
      ). Nearly 58% of PCAs are multifocal and progress along the capsule of the prostate and may not appear as well-defined nodules like other malignant tumors. Therefore, it is difficult to detect lesions accurately using conventional imaging technology (
      • McNeal J.E.
      • Redwine E.A.
      • Freiha F.S.
      • Stamey T.A.
      Zonal distribution of prostatic adenocarcinoma: Correlation with histologic pattern and direction of spread.
      ,
      • Nakashima K.
      • Shiina T.
      • Sakurai M.
      • Enokido K.
      • Endo T.
      • Tsunoda H.
      • Takada E.
      • Umemoto T.
      • Ueno E.
      JSUM ultrasound elastography practice guidelines: Breast.
      ). Meanwhile, color Doppler and power Doppler imaging do not substantially improve the diagnostic accuracy (
      • Beerlage H.
      • Aarnink R.
      • Ruijter E.
      • Witjes J.
      • Wijkstra H.
      • Van D.
      • Kaa C.
      • et al.
      Correlation of transrectal ultrasound, computer analysis of transrectal ultrasound and histopathology of radical prostatectomy specimen.
      ,
      • Rifkin M.
      • Zerhouni E.
      • Gatsonis C.
      • Quint L.
      • Paushter D.
      • Epstein J.
      • Hamper U.
      • Walsh P.C.
      • McNeil B.J.
      Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer.
      ). Pathologic results obtained by TRUS-guided SB remain the mainstay in confirming or ruling out PCA (
      • Rifkin M.
      • Zerhouni E.
      • Gatsonis C.
      • Quint L.
      • Paushter D.
      • Epstein J.
      • Hamper U.
      • Walsh P.C.
      • McNeil B.J.
      Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer.
      ). Prostate biopsy also allows estimation of the aggressiveness of PCA (Gleason score, invasion of capsule or neurovascular bundles) (
      • Kelloff G.J.
      • Choyke P.
      • Coffey D.S.
      Prostate Cancer Imaging Working Group. Challenges in clinical prostate cancer: role of imaging.
      ). When clinical suspicion of PCA persists despite negative biopsies, MRI-targeted biopsies are considered (
      • Correas J.M.
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      • Isidori A.M.
      • Helenon O.
      • Pozza C.
      • Cantisani V.
      • Di Leo N.
      • Maghella F.
      • Rubini A.
      • Drudi F.M.
      • D'Ambrosio F.
      Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal.
      ,
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      • Eiss D.
      • Helenon O.
      Ultrasound elastography of the prostate: state of the art.
      ).
      Because of the inaccuracy of TRUS and the limitations of SB, improved imaging for the detection, localization and staging of PCA is needed. As cancerous tissue in the prostate has a higher stiffness compared with benign tissue, an imaging technique able to assess tissue stiffness would be useful in the diagnosis of PCA. PCA tissue becomes stiffer than the surrounding healthy prostate tissue because of the following changes: an increase in cellular density and microvascularization, destruction of the glandular architecture (
      • Dvorak H.F.
      Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing.
      ) and triggering of wound repair. This process is characterized by stromal reaction (
      • Dvorak H.F.
      Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing.
      ,
      • Tuxhorn J.A.
      • Ayala G.E.
      • Rowley D.R.
      Reactive stroma in prostate cancer progression.
      ) and collagen deposition surrounding the cancer (
      • Tuxhorn J.A.
      • Ayala G.E.
      • Smith M.J.
      • Smith V.C.
      • Dang T.D.
      • Rowley D.R.
      Reactive stroma in human prostate cancer: Induction of myofibroblast phenotype and extracellular matrix remodeling.
      ). Deposition of collagen increases significantly with Gleason grade (
      • Burns-Cox N.
      • Avery N.C.
      • Gingell J.C.
      • Bailey A.J.
      Changes in collagen metabolism in prostate cancer: A host response that may alter progression.
      ,
      • Zhang Y.
      • Nojima S.
      • Nakayama H.
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      • Enza H.
      Characteristics of normal stromal components and their correlation with cancer occurrence in human prostate.
      ) and is linked to a significant reduction in the acinar area in the PCA stroma. All of these changes contribute to the increased stiffness of tissue affected by PCA (
      • Phipps S.
      • Yang T.H.
      • Habib F.K.
      • Reuben R.L.
      • McNeill S.A.
      Measurement of tissue mechanical characteristics to distinguish between benign and malignant prostatic disease.
      ).
      At present, two US elastography techniques have been developed for image the prostate in clinic practice: strain elastography (SE) and shear wave elastography (SWE). Vibroelastography is another dynamic US elastography technique that models viscoelastic properties of the tissue. Although vibroelastography has been tested in clinical patients, it is not widely available (
      • Mahdavi S.S.
      • Moradi M.
      • Wen X.
      • Morris W.J.
      • Salcudean S.E.
      Evaluation of visualization of the prostate gland in vibro-elastography images.
      ). US elastography improves both prostate lesion characterization and PCA detection; in particular, this approach can be extremely useful in the detection of prostate lesions, disclosing lesions on the elasticity map that are not visible on conventional TRUS imaging (iso-echoic lesions) or other imaging modalities such as MRI. It is important to understand that iso-echoic lesions can be detected with prostate elastography, as the displayed information does not rely on backscattered signals. Elastography may therefore have two major indications: to provide improved characterization of prostate lesions and to increase the detection of PCA.

      Transrectal Strain Elastography

      Transrectal SE assesses the differences in tissue strain produced by freehand manual compression, with stiffer tissues having less strain. Transrectal SE represents the distribution of strain and helps differentiate benign from malignant tissue (
      • Nakashima K.
      • Shiina T.
      • Sakurai M.
      • Enokido K.
      • Endo T.
      • Tsunoda H.
      • Takada E.
      • Umemoto T.
      • Ueno E.
      JSUM ultrasound elastography practice guidelines: Breast.
      ). As a novel biomechanical technique, transrectal SE is an improvement over conventional ultrasonic imaging, with better diagnostic value for PCA.
      Transrectal prostate SE is based on the analysis of tissue deformation generated by inducing an external mechanical stress (slight compressions and decompressions of the tissue by the transrectal transducer itself). The deformation needs to be uniform in intensity throughout the gland (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ). A speckle comparison, before and after compression, yields a color-coded map of local tissue deformation or strain, called the elastogram. Tissue stiffness is estimated by visualizing the differences in strain between adjacent regions. The stiffness color scale is automatically distributed from the lowest to the highest strain found in the image plane and displayed as an overlay on the B-mode image. Stiff tissues exhibit reduced strain, whereas soft tissues have higher strain (distortion). A quality index may help ensure appropriate frequency and applied pressure of the manual compressions. Recently, the guidelines and recommendations of the European Federation of Societies for Ultrasound in Medicine and Biology Guidelines (
      • Cosgrove D.
      • Piscaglia F.
      • Bamber J.
      • Bojunga J.
      • Correas J.
      • Gilja O.
      • Klauser A.
      • Sporea I.
      • Calliada F.
      • Cantisani V.
      • D'Onofrio M.
      • Drakonaki E.
      • Fink M.
      • Friedrich-Rust M.
      • Fromageau J.
      • Havre R.
      • Jenssen C.
      • Ohlinger R.
      • Săftoiu A.
      • Schaefer F.
      • Dietrich C.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 2. Clinical applications.
      ) and the Japan Society of Ultrasonics in Medicine (JSUM) (
      Terminology and Diagnostic Criteria Committee, Japan Society of Ultrasonics in Medicine
      Clinical practice guidelines for ultrasound elastography: prostate.
      ) have assessed the clinical use of ultrasound elastography. These documents are intended to form a reference and to guide clinical users in a practical way. The guidelines also give practical advice on its use and interpretation (
      • Bamber J.
      • Cosgrove D.
      • Dietrich C.
      • Fromageau J.
      • Bojunga J.
      • Calliada F.
      • Cantisani V.
      • Correas J.
      • D'Onofrio M.
      • Drakonaki E.
      • Fink M.
      • Friedrich-Rust M.
      • Gilja O.
      • Havre R.
      • Jenssen C.
      • Klauser A.
      • Ohlinger R.
      • Saftoiu A.
      • Schaefer F.
      • Sporea I.
      • Piscaglia F.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 1. Basic principles and technology.
      ,
      • Cosgrove D.
      • Piscaglia F.
      • Bamber J.
      • Bojunga J.
      • Correas J.
      • Gilja O.
      • Klauser A.
      • Sporea I.
      • Calliada F.
      • Cantisani V.
      • D'Onofrio M.
      • Drakonaki E.
      • Fink M.
      • Friedrich-Rust M.
      • Fromageau J.
      • Havre R.
      • Jenssen C.
      • Ohlinger R.
      • Săftoiu A.
      • Schaefer F.
      • Dietrich C.
      EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 2. Clinical applications.
      ).

      Procedure

      No specific preparation is required for transrectal SE, which is conducted after a complete, high-quality TRUS examination in the transverse and sagittal planes. The examination includes measuring the prostate volume, identifying suspicious areas in the gland and analyzing the periprostatic space (including the seminal vesicles). The same transrectal probe is used for both conventional US and SE. A water-filled balloon may be placed between the transducer and the rectal wall to improve the homogeneity of the deformation (
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Endo T.
      • Kandori S.
      • Shimokama T.
      • Ishikawa S.
      Real-time balloon inflation elastography for prostate cancer detection and initial evaluation of clinicopathologic analysis.
      ).
      The patient lies in the left lateral position with bended knees and hip flexion or in the lithotomy position. A cover is placed on the transducer using a moderate amount of coupling gel, and the transducer is slowly inserted into the rectum. The prostate capsule, symmetry, abnormal echogenicity patterns, especially hypo-echoic lesions, calcification and boundary are observed initially on conventional US. The prostate volume is measured and recorded. The entire gland is evaluated from the apex to the base or vice versa, including the seminal vesicles and periprostatic tissues. Color or power Doppler can then be performed if required.
      After conventional imaging, SE is performed. The elastogram is displayed over the B-mode image in a color-coded scale. Various color-coded scales can be used. Most systems have an indicator (quality index) displayed in real time that allows the user to determine if the degree of compression/release is appropriate. The frequency of the small compressions/release should remain constant to generate a continuous series of images. The quality index helps ensure appropriate frequency and pressure of the compression/release. Transrectal SE images are obtained in the transverse plane at up to 30 frames per second. The focus should be placed in the far field of the region of interest (ROI). The ROI should cover the entire prostate gland and the surrounding tissues, but avoid the bladder. Semi-quantitative stiffness information can be derived by measuring the strain ratio between two ROIs (usually one considered as the reference normal prostate tissue and the other as the abnormal area). The amount of compression/release needed for most systems is less than 2%. With use of the quality index (Fig. 1) for the process of compression/release, the pressure and direction of manual vibration are adjusted until stable, repeatable images (prostatic capsule is clear, smooth and symmetrical bilaterally, unless there is capsular extension of the tumor), with the pressure indicator bar displaying good quality are obtained.
      Figure thumbnail gr1
      Fig. 1Most strain elastography systems provide a quality measure or index indicating if the compression/release is optimal. Some examples are provided here. For optimal acquisition, a stable image of high quality is required. Some vendors use a numerical system from 0 to 100, with 100 being the optimal quality. Others use a “bar.” The higher the “bar,” the better is the quality.
      The images and or clips are stored in the system for further analysis. By stepwise scanning of the prostate from base to apex, strain elastography allows detection of stiff regions and provides stiffness comparisons between lesions and the adjacent prostate tissue.
      Recommendation 1. Technical recommendations for optimal acquisition should include minimal preload (pre-compression), focus zone should be placed in the far field of the region of interest, field-of-view size including prostate capsule and some periprostatic tissues but excluding the bladder. Level of evidence (LoE): 5, grade of recommendation (GoR) D; 100% consensus agreement.
      Recommendation 2. It is better if the area of concern can be located in the center of the field of view (for better stress application). LoE: 5, GoR: D; 100% consensus agreement.

      Image interpretation

      Normal SE pattern

      The normal peripheral zone (PZ) of the prostate is of intermediate stiffness regardless of its size, whereas the lateral and basal portions appear slightly stiffer. The elastographic pattern of the transition zone varies with the volume of the gland. The urethra in the verumontanum is expressed as a soft, upside-down V-shaped structure. The SE pattern of the prostate also depends on age-related changes: in young healthy patients, the stiffness of the prostate is usually homogeneous with a soft pattern and the PZ remains soft and homogeneous. However, with advancing age and increasing volume, increasing stiffness is often observed, especially in the inner (transitional zone and central zone) gland. A pericapsular “soft rim artifact” is often seen, corresponding to the capsule of the prostate; its absence may indicate extracapsular extension (ECE) (
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ). Strain elastography can distinguish the elastic properties of different anatomic components of the prostate and identify the variations that occur as the size of the gland increases (
      • Goddi A.
      • Sacchi A.
      • Magistretti G.
      • Almolla J.
      Transrectal real-time elastography of the prostate: Normal patterns.
      ,
      • Westendarp M.
      • Postema A.
      • de la Rosette J.J.
      • Wijkstra H.
      • Laguna M.P.
      Advances in ultrasound techniques for the diagnosis and staging of prostate cancer: Elastography, Doppler ultrasound, ultrasound contrast media, ultrasound quantification media and MRI fusion.
      ).

      Lesion characterization

      SE can produce stiff-appearing artifacts with increasing depth from the transducer. In 2005, three components for an adequate study were described (
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ): (i) The suspicious area is color-coded stiff, thus revealing relatively stiff tissue; (ii) the strain image of the lesion is reproducible; (iii) there is no correlation with a benign lesion, for example, a nodule with benign prostate hyperplasia, stones and so on.
      For improved definition and discrimination of the tissue in the ROI, several scoring systems have been described. The Prostate Imaging Reporting and Data System (PI-RADS) lexicon should be used for terminology and lesion location (
      • Stark J.R.
      • Perner S.
      • Stampfer M.J.
      • Sinnott J.A.
      • Finn S.
      • Isenstein A.S.
      • Ma J.
      • Fiorentino M.
      • Kurth T.
      • Loda M.
      • Giovannucci E.L.
      • Rubin M.A.
      • Mucci L.A.
      Gleason score and lethal prostate cancer: Does 3 + 4 = 4 + 3?.
      ).
      A five-point subjective scale was developed based on the degree and distribution of strain on SE in relation to simultaneously displayed hypo-echoic areas on baseline US (Fig. 2) (
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      ). The scoring system is as follows (assuming that the stiffer tissue is displayed in blue):
      • Score 1: Normal appearance (homogeneous strain, the entire gland is evenly shaded in green)
      • Score 2: Probably normal (symmetric heterogeneous strain, the gland is a symmetric mosaic pattern of green and blue)
      • Score 3: Indeterminate (focal asymmetric lesion without strain not related to a hypo-echoic lesion, the focal asymmetric lesion in blue [stiff])
      • Score 4: Probably carcinoma (strain at the periphery of the hypo-echoic lesion with sparing of the center of the lesion, the peripheral part of lesion in green and the central part in blue [stiff])
      • Score 5: Definitely carcinoma (no strain in the entire hypo-echoic lesion or in the surrounding area, the entire lesion in blue [stiff]).
      Figure thumbnail gr2
      Fig. 2Five-point color-coded scoring system proposed by
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      for interpreting prostate strain elastography, where red is soft and blue is stiff, as follows: (a) Score 1: normal appearance (homogeneous strain, the entire gland evenly shaded in green/red. (b) Score 2: Probably normal (symmetric heterogeneous strain, the gland has a symmetrical mosaic pattern of green and blue). (c) Indeterminate (focal asymmetric lesion without strain not related to hypo-echoic lesion; arrows point to the focal asymmetric lesion in blue). (d) Probably carcinoma (strain at the periphery of the hypo-echoic lesion with sparing of the center of the lesion; the peripheral part of the lesion is green and the central part blue; arrows point to the lesion). (e) Definitely carcinoma (no strain in the entire hypo-echoic lesion or in the surrounding area; the entire lesion is blue; arrows point to the lesion).
      Images courtesy of Dr. Hui-Xiong Xu.
      At a cutoff value of 3 (displaying focal asymmetric lesion without strain not related to hypo-echoic lesion), SE had 68% sensitivity, 81% specificity and 76% accuracy (
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      ). SE was comparable to power Doppler US (70% sensitivity, 75% specificity and 73% accuracy) and had significantly higher sensitivity than B-mode US (68% vs. 50%) using this scoring system. The combination of SE with power Doppler US further increased the sensitivity to 78%. The rate of detection of targeted biopsies from suspicious areas with either SE or power Doppler US was 29% by patient and was comparable to that of SB (31%). The per core detection rate of SE + power Doppler US targeted biopsy cores (50%) was significantly higher than that of the SB cores (15%).
      Another scoring system was proposed by the Innsbruck group. The most recent scoring system was developed without including the central gland findings (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ) (Fig. 3).
      Figure thumbnail gr3
      Fig. 3Color-coded scoring system proposed by
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      . This scale is based on blue as stiff and red as soft using transrectal SE (a) Score 1: There is no blue area or star-like blue in the peripheral gland. (b) The mosaic or a small symmetric blue area is less than 5 mm. (c) A small symmetric blue area in bilateral peripheral gland; the diameter of the blue area is ≥5 mm. (d) Asymmetric blue area in the bilateral peripheral glands; the diameter of the blue area is ≥5 mm. (e) Asymmetric blue area in>50%, the blue area ≥50% of a single peripheral gland.
      Images courtesy of Dr. Hui-Xiong Xu.
      The ROI of SE is set to approximately 1 cm at the edge of the largest transverse image. Using a color scale on which red is soft and blue is stiff, the following scoring system was proposed.
      • Score 1: No blue area or star-like blue in the peripheral gland
      • Score 2: Mosaic or a small symmetric blue area bilaterally in the outer gland (the blue area is <5 mm in diameter)
      • Score 3: A small symmetric blue area in the outer gland (diameter of blue area ≥5 mm)
      • Score 4: Asymmetric blue area in the outer gland (diameter of blue area ≥5 mm)
      • Score 5: Asymmetric blue area in the outer gland (blue area >50%, blue area ≥50% of single outer gland area)
      With this scoring method, the area under the curve (AUC) is 0.729 (95% confidence interval [CI]: 0.648, 0.810), and the best cutoff value of the transrectal real-time elastographyscore is 3. The sensitivity, specificity and accuracy in diagnosis of PCA are 68.6%, 69.4% and 69.2%, respectively, with biopsy as the reference standard (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ).

      Semi-quantification and histogram

      The strain ratio index (SRI) using SE, which is a semi-quantitative measurement tool comparing the strain value of the target lesion with that of the background tissue, has been investigated (Fig. 4). The peak strain ratio index is found to be more useful when it is calculated as the strain ratio (SR) of the reference normal prostate tissue to the SR of the peak stiffest region in the lesion (
      • Zhang Y.
      • Tang J.
      • Li Y.
      • Fei X.
      • Lv F.
      • Hea E.
      • Li Q.
      • Shi H.
      Differentiation of prostate cancer from benign lesions using strain index of transrectal real-time tissue elastography.
      ,
      • Zhang Y.
      • Tang J.
      • Li Y.M.
      • Fei X.
      • He E.H.
      • Li Q.Y.
      • Shi H.Y.
      The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography.
      ). To reduce false-positive findings using SE of the prostate, Zhang et al. investigated the SRI using SE. They found a significant difference in peak strain index values between benign and malignant lesions. Furthermore, the cutoff 17.4 peak strain index value yielded the highest sensitivity (74.5%) and specificity (83.3%) with an AUC of 0.90 for discriminating PCA (
      • Zhang Y.
      • Tang J.
      • Li Y.
      • Fei X.
      • Lv F.
      • Hea E.
      • Li Q.
      • Shi H.
      Differentiation of prostate cancer from benign lesions using strain index of transrectal real-time tissue elastography.
      ,
      • Zhang Y.
      • Tang J.
      • Li Y.M.
      • Fei X.
      • He E.H.
      • Li Q.Y.
      • Shi H.Y.
      The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography.
      ).
      Figure thumbnail gr4
      Fig. 4To obtain semi-quantitative data, the strain ratio can be calculated. This method compares the stiffness of a lesion with that of normal prostate tissue. Region of interest (ROI) A is placed in the stiff lesion in the left apex of the prostate. ROI B is placed in normal prostate tissue. The strain of ROI A is 0.01%, whereas that of B is 0.40%, yielding a strain ratio of 43.66 suggestive of a very stiff lesion, highly suspicious for a prostate cancer.
      Courtesy of Dr. Marko Brock.
      Mechanical testing results revealed that the viscosity parameter for cancerous prostate tissue is greater than that derived from normal tissue by a factor of approximately 2.4. The clinical impact of the increased viscosity in cancerous tissue is unknown. It was also determined that a significant difference exists between normal and cancerous prostate tissue stiffness (
      • Hoyt K.
      • Castaneda B.
      • Zhang M.
      • Nigwekar P.
      • di Sant'agnese P.A.
      • Joseph J.V.
      • Strang J.
      • Rubens D.J.
      • Parker K.J.
      Tissue elasticity properties as biomarkers for prostate cancer.
      ). The elastic modulus was greater in the tissue with a Gleason score of 8 than in the other tissue, and was significantly greater in the tissue with a tumor volume >5 cm3 than in the other tissue (
      • Ahn B.M.
      • Kim J.
      • Ian L.
      • Rha K.H.
      • Kim H.J.
      Mechanical property characterization of prostate cancer using a minimally motorized indenter in an ex vivo indentation experiment.
      ). Qualitative sonoelastographic results showed promise for PCA detection and may prove to be an effective adjunct imaging technique for biopsy guidance. However, the fact that base and mid-gland are twice as stiff as the apex should be considered (
      • Ahn B.M.
      • Kim J.
      • Ian L.
      • Rha K.H.
      • Kim H.J.
      Mechanical property characterization of prostate cancer using a minimally motorized indenter in an ex vivo indentation experiment.
      ).
      Recommendation 3. Although several methods for interpreting SE of the prostate have been proposed, a uniformly accepted scoring system has not been established. Any of the proposed scoring systems can be used. LoE: 5, GoR: D; 100% consensus agreement.
      Recommendation 4. The PI-RADS lexicon terminology and lesion location should be used in reporting results. LoE: 5, GoR: D; 100% consensus agreement.

      Reproducibility and learning curve

      Strain elastography of the prostate can be learned quickly by an inexperienced examiner, and the examination itself is not very time consuming (
      • Heinzelbecker J.
      • Weiss C.
      • Pelzer A.E.
      A learning curve assessment of real-time sonoelastography of the prostate.
      ). However, the manual compression and release are relatively uncontrolled elements of SE with wide variability. Thus, images affected by artifacts have been found in up to 32% of cases. Standardized compression using real-time balloon inflation has improved the quality of elastographic images (
      • Matsumura T.
      • Tsutsumi M.
      • Miyagawa T.
      • Fujihara Y.
      • Tonomura A.
      • Osaka T.
      • Shinomura R.
      • Mitake T.
      • Kanda H.
      • Shiina T.
      Clinical performance of balloon-inflation-based elasticity imaging for prostate cancer diagnosis.
      ) This technique enables a twofold wider uniform stress field compared with that for the free-hand method (
      • Matsumura T.
      • Tsutsumi M.
      • Miyagawa T.
      • Fujihara Y.
      • Tonomura A.
      • Osaka T.
      • Shinomura R.
      • Mitake T.
      • Kanda H.
      • Shiina T.
      Clinical performance of balloon-inflation-based elasticity imaging for prostate cancer diagnosis.
      ). The size of the prostate and position of the stiffness box may induce some variability. Training should include both assessments of both qualitative and quantitative parameters for a number of examinations under supervision.
      Recommendation 5. Although it is generally accepted that there is a learning curve in the performance of SE prostate imaging, no established standardized training procedure has been proposed. LoE: 5, GoR: D; 100% consensus agreement.
      Recommendation 6. The operator should be trained in prostate TRUS and transrectal US-guided biopsies and have adequate training and experience with the US machine and the specific SE technique used. LoE: 5, GoR: D; 100% consensus agreement.

      Review of the literature

      Several different applications of SE of the prostate have been reported, including (i) characterization of abnormal regions detected on B-mode US, color Doppler US and/or power Doppler US, or MRI/multiparametric (mp) MRI, detection of lesions not seen with any imaging technique; (ii) staging of PCA; and (iii) biopsy targeting.
      Table 1, Table 2, Table 3, Table 4 review the published articles.
      Table 1Elastography studies prior to radical prostatectomy assessing diagnostic performance per patient and per core
      ReferenceYearTechniqueNo. of patientsNo. of PCA lesionsSen (%)Spe (%)PPV (%)NPV (%)Acc (%)
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      2007Strain16358792809592
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      2007Strain51778260
      • Sumura M.
      • Shigeno K.
      • Hyuga T.
      • Yoneda T.
      • Shiina H.
      • Igawa M.
      Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study.
      2007Strain177488
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      2008Strain1094517577885976
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Endo T.
      • Kandori S.
      • Shimokama T.
      • Ishikawa S.
      Real-time balloon inflation elastography for prostate cancer detection and initial evaluation of clinicopathologic analysis.
      2010Strain551157389818483
      • Walz J.
      • Marcy M.
      • Maubon T.
      • Brunelle S.
      • Laroche J.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Real time elastography in the diagnosis of prostate cancer: Comparison of preoperative imaging and histology after radical prostatectomy.
      ,
      • Walz J.
      • Marcy M.
      • Pianna J.T.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Identification of the prostate cancer index lesion by real-time elastography: Considerations for focal therapy of prostate cancer.
      2011Strain28887379678377
      • Walz J.
      • Marcy M.
      • Maubon T.
      • Brunelle S.
      • Laroche J.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Real time elastography in the diagnosis of prostate cancer: Comparison of preoperative imaging and histology after radical prostatectomy.
      ,
      • Walz J.
      • Marcy M.
      • Pianna J.T.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Identification of the prostate cancer index lesion by real-time elastography: Considerations for focal therapy of prostate cancer.
      2011Strain3272816785
      • Brock M.
      • von Bodman C.
      • Sommerer F.
      • Loppenberg B.
      • Klein T.
      • Deix T.
      • Palisaar J.R.
      • Noldus J.
      • Eggert T.
      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.
      2011Strain2298946672815368
      • Junker D.
      • Schafer G.
      • Aigner F.
      • Schullian P.
      • Pallwein-Prettner L.
      • Bektic J.
      • Horninger W.
      • Halpern E.J.
      • Frauscher F.
      Potentials and limitations of real-time elastography for prostate cancer detection: A whole-mount step section analysis.
      2012Strain394883
      • Pelzer A.E.
      • Heinzelbecker J.
      • Weiss C.
      • Fruhbauer D.
      • Weidner A.M.
      • Kirchner M.
      • Stroebel P.
      • Schoenberg S.O.
      • Dinter D.J.
      Real-time sonoelastography compared to magnetic resonance imaging using four different modalities at 3.0 T in the detection of prostate cancer: Strength and weaknesses.
      2013Strain50
      • Brock M.
      • Eggert T.
      • Palisaar R.J.
      • Roghmann F.
      • Braun K.
      • Loppenberg B.
      • Sommerer F.
      • Noldus J.
      • von Bodman C.
      Multiparametric ultrasound of the prostate: Adding contrast enhanced ultrasound to real-time elastography to detect histopathologically confirmed cancer.
      2013Strain86564974785162
      • Junker D.
      • Schafer G.
      • Kobel C.
      • Kremser C.
      • Bektic J.
      • Jaschke W.
      • Aigner F.
      Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis.
      ,
      • Junker D.
      • Zordo D.
      • Quentin M.
      • Ladurner M.
      • Bektic J.
      • Horniger M.
      • Jaschke W.
      • Aigner F.
      Real-time elastography of the prostate.
      2014Strain396167
      • Zhu Y.
      • Chen Y.
      • Qi T.
      • Jiang J.
      • Qi J.
      • Yu Y.
      • Yao X.
      • Guan W.
      Prostate cancer detection with real-time elastography using a bi-plane transducer: Comparison with step section radical prostatectomy pathology.
      2014Strain56678983
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      2015SWE60608169678274
      PCA = prostate cancer; Sen = sensitivity; Spe = specificity; PPV = positive predictive value; NPV = negative predictive value; Acc = accuracy; SWE = shear wave elastography.
      Table 2Strain and shear wave elastography studies prior to systematic biopsy assessing diagnostic performance per patient and per core
      ReferenceYearTech-niqueNNo. of PCA lesionsPer patient (%)No. of coresPer core (%)
      SenSpePPVNPVAccSenSpePPVNPVAcc
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      2005Strain404151849065167496861
      • Pallwein L.
      • Mitterberger M.
      • Pinggera G.
      • Aigner F.
      • Pedross F.
      • Gradl J.
      • Pelzer A.
      • Bartsch G.
      • Frauscher F.
      Sonoelastography of the prostate: Comparison with systematic biopsy findings in 492 patients.
      2008Strain49212589726291772,9526989519587
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      2008Strain1074068816881769407577885976
      • Miyagawa T.
      • Tsutsumi M.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Miyanaga N.
      • Akaza H.
      Real-time elastography for the diagnosis of prostate cancer: Evaluation of elastographic moving images.
      2009Strain31195731,5395053228153
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      2012Strain17891511,0686168328968
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      2012SWE53261003189696699996
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      2013SWE50336269289958391
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      2015SWE97264381139570
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      2015SWE1846893635994741,0589685489985
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      2015SWE95389567499058
      PCA = prostate cancer; Sen = sensitivity; Spe = specificity; PPV = positive predictive value; NPV = negative predictive value; Acc = accuracy.
      Table 3SWE stiffness for benign and malignant tissues (for all and Gleason score 6–9 lesions) for each SWE study where available.
      ReferenceYearNNo. of PCA lesionsBenign tissue
      Benign tissues = all tissues, normal tissues, Inflam and PIN.
      For Barr et al. and Correas et al. Gleason Score 6 lesions were considered PCA.
      pMalignant tissue
      For Boem et al., Ahmad et al. and Woo et al., Gleason score 6 lesions were considered non-cancerous lesions.
      AllNormalInflamPINAllGS 6GS 7GS 8GS 9
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      2012532622 ± 12
      Mean ± standard deviation.
      27.3 ± 15.50.000158 ± 21
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      2013503375 ± 4783 ± 390.0001134 ± 5895 ± 29163 ± 63113 ± 20
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      2015972633 ± 1832 ± 1746 ± 3826 ± 110.00255 ± 4633 ± 1955 ± 4957 ± 4088 ± 64
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      20151846821 ± 6<0.000160 ± 2045 ± 760 ± 2070 ± 29125 ± 29
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      2015953842 ± 20<0.000188 ± 40
      SWE = shear wave elastography; PCA = prostate cancer; Inflam = inflammation; PIN = prostatic intraepithelial neoplasia; GS = Gleason score.
      Benign tissues = all tissues, normal tissues, Inflam and PIN.
      For Barr et al. and Correas et al. Gleason Score 6 lesions were considered PCA.
      For Boem et al., Ahmad et al. and Woo et al., Gleason score 6 lesions were considered non-cancerous lesions.
      § Mean ± standard deviation.
      Table 4Detection rate per patient and per core of strain and shear wave elastography with systematic biopsies and targeted biopsies
      ReferenceYearTech-niqueNStudy designNo. of SBsNo. of TBsDR per patient (%)DR per core (%)
      SBTBSB + TBSBTBSB + TB
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      2005Strain404SB + TB10≤43137
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      2007Strain230SB + TB10≤52530356138
      • Nelson E.D.
      • Slotoroff C.B.
      • Gomella L.G.
      • Halpern E.J.
      Targeted biopsy of the prostate: The impact of color Doppler imaging and elastography on prostate cancer detection and Gleason score.
      2007Strain137SB + TB8≤4402444122014
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      2008Strain107SB + TB10≤4312937155519
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      2010Strain94SB + TB10≤51921285248
      • Kapoor A.
      • Kapoor A.
      • Mahajan G.
      • Sidhu B.S.
      Real-time elastography in the detection of prostate cancer in patients with raised PSA level.
      2011Strain15SB + TB10≤4677373376743
      • Ganzer R.
      • Brandtner A.
      • Wieland W.F.
      • Fritsche H.M.
      Prospective blinded comparison of real-time sonoelastography targeted versus randomised biopsy of the prostate in the primary and re-biopsy setting.
      2012Strain139SB + TB10≤4473253112214
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      2012Strain353Mixed10≤10395145
      • Zhang Y.
      • Tang J.
      • Li Y.
      • Fei X.
      • Lv F.
      • Hea E.
      • Li Q.
      • Shi H.
      Differentiation of prostate cancer from benign lesions using strain index of transrectal real-time tissue elastography.
      ,
      • Zhang Y.
      • Tang J.
      • Li Y.M.
      • Fei X.
      • He E.H.
      • Li Q.Y.
      • Shi H.Y.
      The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography.
      2012Strain148SB + TB12≤44144147619
      • Taverna G.
      • Magnoni P.
      • Giusti G.
      • Seveso M.
      • Benetti A.
      • Hurle R.
      • Colombo P.
      • Minuti F.
      • Grizzi F.
      • Graziotti P.
      Impact of real-time elastography versus systematic prostate biopsy method on cancer detection rate in men with a serum prostate-specific antigen between 2.5 and 10 ng/mL.
      2013Strain102SB1332133
      • Salomon G.
      • Drews N.
      • Autier P.
      • Beckmann A.
      • Heinzer H.
      • Hansen J.
      • Michl U.
      • Schlomm T.
      • Haese A.
      • Steuber T.
      • Graefen M.
      • Becker A.
      Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.
      2014Strain1024SB + TB10≤4392946
      • Nygard Y.
      • Haukaas S.A.
      • Halvorsen O.J.
      • Gravdal K.
      • Frugard J.
      • Akslen L.A.
      • Beisland C.
      A positive real-time elastography is an independent marker for detection of high-risk prostate cancers in the primary biopsy setting.
      2014Strain127SB + TB10–12≤4482450182820
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      2015SWE95SB + TB6–18≤33628409119
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      2015Strain259SB + TB10–14≤46394
      DR = detection rate; SWE = shear wave elastography; DR = detection rate; SB = systematic biopsy; TB = targeted biopsy.

      Characterization of prostatic lesions

      Strain elastography is the most studied elastography method for PCA localization. The internal texture of the normal prostate has a normal glandular appearance. In PCA, however, the cancer cells induce a stromal reaction, and the invasion of cancer cells causes the normal glandular appearance to disappear. As a result, the tissue invaded by cancer cells is stiffer than normal tissue or benign lesions (
      • Krouskop T.A.
      • Wheeler T.M.
      • Kallel F.
      • Garra B.S.
      • Hall T.
      Elastic moduli of breast and prostate tissues under compression.
      ). This stiffening is the underlying characteristic that elastography exploits for the detection and characterization of prostate lesions. The sensitivity, specificity and accuracy of SE for prostate lesions have been reported as 68%, 81% and 76%, respectively (
      • Kamoi K.
      • Okihara K.
      • Ochiai A.
      • Ukimura O.
      • Mizutani Y.
      • Kawauchi A.
      • Miki T.
      The utility of transrectal real-time elastography in the diagnosis of prostate cancer.
      ), using biopsy as the reference. In the per-patient analysis, SE sensitivity was 51%, specificity 75%, positive predictive value (PPV) 64% and negative predictive value (NPV) 64%, whereas the per-core analysis had a sensitivity of 36%, specificity 93%, PPV 72% and NPV 74%.
      Comparison of the diagnostic accuracy of B-mode US and SE in the detection of peripheral zone tumors revealed a significant difference, with improved PCA detection in SE with a B-mode sensitivity of 48%, specificity of 81% and accuracy of 64%, whereas SE had a sensitivity of 66%, specificity of 78% and accuracy of 72%. (
      • Ferrari F.
      • Scorzelli A.
      • Megliola A.
      • Drudi F.
      • Trovarelli S.
      • Ponchietti R.
      Real-time elastography in the diagnosis of prostate tumor.
      ). A recent meta-analysis investigated the diagnostic performance of SE in the diagnosis of PCA in 7 studies with surgical pathology as the reference: The pooled sensitivity and specificity of SE were 0.72 (95% CI: 0.70–0.74) and 0.76 (95% CI: 0.74–0.78), respectively (
      • Zhang B.
      • Ma X.
      • Zhan W.
      • Zhu F.
      • Li M.
      • Huang J.
      • Li Y.
      • Xue L.
      • Liu L.
      • Wei Y.
      Real-time elastography in the diagnosis of patients suspected of having prostate cancer: A meta-analysis.
      ). However, there remains controversy, and some recent studies reported an inability to differentiate prostate cancer from chronic prostatitis. Benign diseases like prostatitis, prostate lithiasis, fibrosis, atrophy, adenomyomatosis and benign prostate hyperplasia may be associated with increased tissue stiffness and, therefore, may be difficult to distinguish from PCA. This can be responsible for the low positive predictive value of only 39% for men with PSA serum values <4 ng/mL (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ).
      Recommendation 7. Strain elastography should not be interpreted without considering the conventional B-mode findings. LoE: 5, GoR: B; 100% consensus agreement.

      Cancer detection

      Cancer detection in primary biopsy

      Table 1 summarizes elastography studies using radical prostatectomy specimens as the reference standard. Table 2 summarizes elastography (SE and SWE) studies prior to systematic biopsy assessing diagnostic performance per patient and per core. In the clinical application of SE-guided biopsy, stiff areas with a diameter ≥5 mm on elasticity imaging are considered malignant (
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ). The false-negative results for SE are in the range of 15.9%. Some authors concluded that SE is superior to DRE or TRUS only. In a prospective study (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ), the prostate cancer detection rate was significantly higher in patients who underwent biopsy with SE guidance than in those who underwent transrectal US guided biopsy at 51.1% (91/178) versus 39.4% (69/175) (p = 0.027). The overall PCA detection rate was 37.4% in all patients, with 84.1% of those cancers detected by SE-guided biopsies and 64.2% by conventional US-guided biopsies (
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ). In another study, a per-patient detection rate of 30% for SE-targeted biopsies was achieved, whereas 10-core SB detected PCA in 25% of their 230 patients (
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ). A further increase of 13.9% in PCA detection per patient was obtained by SE-guided biopsy in comparison with SB (49.1% vs. 35.2%) (
      • Wang R.
      • Chen J.J.
      • Hu B.
      Transrectal real-time elastography-guided transperineal prostate biopsy as an improved tool for prostate cancer diagnosis.
      ). Positive cancer cores were obtained in 24% of SE targeted cores compared with 5.1% in SB cores (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ). In another study, the overall sensitivity and specificity in detection of prostate cancer were 60.8% and 68.4% for SE versus 15% and 92.3% for B-mode US, respectively (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ). Therefore, in general, SE should be used in combination with TRUS to further increase the detection rate because of the high frequency of false-positive results (i.e., ≤24.2%) for SE (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • Miyagawa T.
      • Tsutsumi M.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Miyanaga N.
      • Akaza H.
      Real-time elastography for the diagnosis of prostate cancer: Evaluation of elastographic moving images.
      ). Inflammatory foci and areas of atrophy in the prostate are regarded as the most common reasons for false-positive SE results (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Pinggera G.
      • Aigner F.
      • Pedross F.
      • Gradl J.
      • Pelzer A.
      • Bartsch G.
      • Frauscher F.
      Sonoelastography of the prostate: Comparison with systematic biopsy findings in 492 patients.
      ).
      Comparison of pre-operative SE images with whole-mount sections after radical prostatectomy to evaluate the accuracy of elastography revealed a sensitivity of 49%–87%, a specificity of 60%–92% for correct PCA localization, an overall PPV of 67%–88% and an NPV of 44%–95% (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ;
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ,
      • Walz J.
      • Marcy M.
      • Maubon T.
      • Brunelle S.
      • Laroche J.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Real time elastography in the diagnosis of prostate cancer: Comparison of preoperative imaging and histology after radical prostatectomy.
      ,
      • Walz J.
      • Marcy M.
      • Pianna J.T.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Identification of the prostate cancer index lesion by real-time elastography: Considerations for focal therapy of prostate cancer.
      ). Overall sensitivity and specificity in the detection of prostate cancer were 60.8% and 68.4% for SE versus 15% and 92.3% for B-mode US, respectively.
      Recommendation 8. The addition of SE of the prostate can increase the PCA detection rate (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ,
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ,
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      ,
      • Wang R.
      • Chen J.J.
      • Hu B.
      Transrectal real-time elastography-guided transperineal prostate biopsy as an improved tool for prostate cancer diagnosis.
      ). LoE: 1C, GoR: B; 100% consensus agreement.
      Recommendation 9. The addition of SE of the prostate increases the positive biopsy rate compared with that of TRUS (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ,
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Horninger W.
      • Aigner F.
      • Bartsch G.
      • Gradl J.
      • Schurich M.
      • Pedross F.
      • Frauscher F.
      Comparison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Struve P.
      • Pinggera G.
      • Horninger W.
      • Bartsch G.
      • Aigner F.
      • Lorenz A.
      • Pedross F.
      • Frauscher F.
      Real-time elastography for detecting prostate cancer: preliminary experience.
      ,
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      ,
      • Wang R.
      • Chen J.J.
      • Hu B.
      Transrectal real-time elastography-guided transperineal prostate biopsy as an improved tool for prostate cancer diagnosis.
      ). LoE: 1C, GoR: B; 100% consensus agreement.
      Recommendation 10. Strain elastography of the prostate is of limited value in the detection of small cancers and may miss carcinomas with a lower Gleason score (
      • Aigner F.
      • Schafer G.
      • Steiner E.
      • Jaschke W.
      • Horninger W.
      • Herrmann T.R.
      • Nagele U.
      • Halpern E.J.
      • Frauscher F.
      Value of enhanced transrectal ultrasound targeted biopsy for prostate cancer diagnosis: a retrospective data analysis.
      ,
      • Junker D.
      • Schafer G.
      • Aigner F.
      • Schullian P.
      • Pallwein-Prettner L.
      • Bektic J.
      • Horninger W.
      • Halpern E.J.
      • Frauscher F.
      Potentials and limitations of real-time elastography for prostate cancer detection: A whole-mount step section analysis.
      ). LoE: 2B, GoR: B; 100% consensus agreement.
      Recommendation 11. Strain elastography targeted biopsies should always be performed with standard systematic biopsies (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • Miyagawa T.
      • Tsutsumi M.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Miyanaga N.
      • Akaza H.
      Real-time elastography for the diagnosis of prostate cancer: Evaluation of elastographic moving images.
      ). LoE: 1B, GoR: B; 100% consensus agreement.
      Recommendation 12. Strain elastography cannot be used as a decision tool to rule out cancer without a biopsy. LoE: 5, GoR: C; 100% consensus agreement.

      Influencing factors

      Prostate volume

      The detection rates of SE for PCA might be related to prostate volume, with a higher accuracy in those with smaller volume (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ). This result is supported by whole-mount pathology section analysis (
      • Junker D.
      • Schafer G.
      • Kobel C.
      • Kremser C.
      • Bektic J.
      • Jaschke W.
      • Aigner F.
      Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis.
      ,
      • Junker D.
      • Zordo D.
      • Quentin M.
      • Ladurner M.
      • Bektic J.
      • Horniger M.
      • Jaschke W.
      • Aigner F.
      Real-time elastography of the prostate.
      ).
      Tumor size and volume. The PCA detection rates for SE are also associated with tumor size and tumor volume. In a whole-mount section analysis, the detection rates for SE were 9.7% for cancers with a maximum diameter of 0–5 mm, 27% for those 6–10 mm, 70.6% for those 11–20 mm and 100% for those >20 mm (
      • Junker D.
      • Schafer G.
      • Aigner F.
      • Schullian P.
      • Pallwein-Prettner L.
      • Bektic J.
      • Horninger W.
      • Halpern E.J.
      • Frauscher F.
      Potentials and limitations of real-time elastography for prostate cancer detection: A whole-mount step section analysis.
      ). With respect to tumor volume, the detection rates were 83.3% for tumor volume ≥0.2 cm3 and 91.2% for tumor volume ≥0.5 cm3 (
      • Junker D.
      • Schafer G.
      • Aigner F.
      • Schullian P.
      • Pallwein-Prettner L.
      • Bektic J.
      • Horninger W.
      • Halpern E.J.
      • Frauscher F.
      Potentials and limitations of real-time elastography for prostate cancer detection: A whole-mount step section analysis.
      ). Another study determined that tumors with a volume <0.5 cm3 are less well detected by SE (detection rate of = 40%) than tumors with a volume ≥0.5 cm3 (detection rate = 80%) by SE (
      • Aigner F.
      • Schafer G.
      • Steiner E.
      • Jaschke W.
      • Horninger W.
      • Herrmann T.R.
      • Nagele U.
      • Halpern E.J.
      • Frauscher F.
      Value of enhanced transrectal ultrasound targeted biopsy for prostate cancer diagnosis: a retrospective data analysis.
      ).
      Recommendation 13. The accuracy of prostate lesion characterization is higher in larger tumors (
      • Junker D.
      • Schafer G.
      • Aigner F.
      • Schullian P.
      • Pallwein-Prettner L.
      • Bektic J.
      • Horninger W.
      • Halpern E.J.
      • Frauscher F.
      Potentials and limitations of real-time elastography for prostate cancer detection: A whole-mount step section analysis.
      ,
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ). LoE: 1C, GoR: B; 100% consensus agreement.
      Tumor location. Strain elastography may have limitations in detecting PCA in the transitional zone (TZ) and anterior gland in larger prostates, and it may have problems in diagnosing PCA with little architecture change of the normal glandular anatomy (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ). The sensitivity for tumor detection ranged from 84%–94% for anterior tumors to 76%–85% and 57%–60% for tumors of the middle and posterior regions, respectively (
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      ). In addition, the sensitivity of PCA detection might be better at the apex (60%–95%) than at the prostatic base (31.6%–75%) when using SE. This might be due to the fact that compression and decompression of smaller volumes at the apex might be more sufficient (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ).
      Recommendation 14. Diagnostic performance is reduced in anterior lesions but may vary with different populations (Japanese) (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ,
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      ). LoE: 2B, GoR: C; 100% consensus agreement.
      PSA levels. The SE detection rate might be related to PSA level. A higher PSA level is associated with higher sensitivity for both SE and SE + TRUS (
      • Miyagawa T.
      • Tsutsumi M.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Miyanaga N.
      • Akaza H.
      Real-time elastography for the diagnosis of prostate cancer: Evaluation of elastographic moving images.
      ), whereas SE-targeted biopsies detected nearly the same proportion of PCAs (19%–21%) as a systematic 10-core biopsy in a screening population with PSA between 1.25 and 4.00 ng/mL and a free-to-total PSA ratio <18% (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ). Other authors argue that the accuracy of SE is higher for those with PSA ranging from 4 to 10 ng/mL than for those with PSA >10 ng/mL (85.3% vs. 66.7%) (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ). However, some authors found that the detection rate for PCA with SE is independent of PSA serum values (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ).
      Recommendation 15. There is not sufficient evidence to suggest use of the PSA value for interpretation of SE of the prostate (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ,
      • Miyagawa T.
      • Tsutsumi M.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Miyanaga N.
      • Akaza H.
      Real-time elastography for the diagnosis of prostate cancer: Evaluation of elastographic moving images.
      ,
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ). LoE: 3B, GoR: C; 100% consensus agreement.

      Gleason score

      The Gleason score is one of the most frequently used histologic grading systems for PCA, and the prognosis of PCA is closely related to the Gleason score. The progression and fatality rates of Gleason score 6 are much lower than those of Gleason scores ≥7 (
      • Albertsen P.C.
      • Hanley J.A.
      • Fine J.
      Gleason score predicted mortality rate to 20 years for untreated early prostate cancer.
      ,
      • Stark J.R.
      • Perner S.
      • Stampfer M.J.
      • Sinnott J.A.
      • Finn S.
      • Isenstein A.S.
      • Ma J.
      • Fiorentino M.
      • Kurth T.
      • Loda M.
      • Giovannucci E.L.
      • Rubin M.A.
      • Mucci L.A.
      Gleason score and lethal prostate cancer: Does 3 + 4 = 4 + 3?.
      ). Some studies (
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      ) reported that the SE detection rate of prostate cancer with a higher Gleason score was higher than that of PCA with a lower Gleason score. This may be explained by the higher cell density of high-grade tumors resulting in stiffer tissue. Positive detection rates of PCA in Gleason scores 6, 7 and 8–9 were reported as 60%, 69.2% and 100%, respectively (
      • Sumura M.
      • Shigeno K.
      • Hyuga T.
      • Yoneda T.
      • Shiina H.
      • Igawa M.
      Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study.
      ). The accuracy for Gleason scores ≤6 and >7 was 66.1% and 70.8%, respectively (
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ). Detection rates for Gleason scores >7 were between 93% and 100%, respectively (
      • Pallwein L.
      • Mitterberger M.
      • Pinggera G.
      • Aigner F.
      • Pedross F.
      • Gradl J.
      • Pelzer A.
      • Bartsch G.
      • Frauscher F.
      Sonoelastography of the prostate: Comparison with systematic biopsy findings in 492 patients.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ). However, the SE detection rate was lower for high-grade tumors (
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Kawazoe N.
      • Ishikawa S.
      • Shimokama T.
      • Shiina T.
      • Miyanaga N.
      • Akaza H.
      The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: Clinicopathological analysis.
      ,
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Endo T.
      • Kandori S.
      • Shimokama T.
      • Ishikawa S.
      Real-time balloon inflation elastography for prostate cancer detection and initial evaluation of clinicopathologic analysis.
      ). When their scoring system was used to rate suspicion, there was no significant difference between the mean scores for Gleason <7 and Gleason ≥7 (
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ).
      As mentioned, the detection rate is influenced by prostate volume, tumor size, tumor location, PSA levels and Gleason score; however, each factor influences the others. There is so far no multivariate analysis on which factor contributes most to tumor detection by SE.
      Recommendation 16. The sensitivity of SE of the prostate seems to be better in lesions with a higher Gleason score (
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      ,
      • Albertsen P.C.
      • Hanley J.A.
      • Fine J.
      Gleason score predicted mortality rate to 20 years for untreated early prostate cancer.
      ,
      • Brock M.
      • von Bodman C.
      • Palisaar R.J.
      • Loppenberg B.
      • Sommerer F.
      • Deix T.
      • Noldus J.
      • Eggert T.
      The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: A prospective study of 353 patients.
      ,
      • Pallwein L.
      • Mitterberger M.
      • Pinggera G.
      • Aigner F.
      • Pedross F.
      • Gradl J.
      • Pelzer A.
      • Bartsch G.
      • Frauscher F.
      Sonoelastography of the prostate: Comparison with systematic biopsy findings in 492 patients.
      ,
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ,
      • Stark J.R.
      • Perner S.
      • Stampfer M.J.
      • Sinnott J.A.
      • Finn S.
      • Isenstein A.S.
      • Ma J.
      • Fiorentino M.
      • Kurth T.
      • Loda M.
      • Giovannucci E.L.
      • Rubin M.A.
      • Mucci L.A.
      Gleason score and lethal prostate cancer: Does 3 + 4 = 4 + 3?.
      ,
      • Sumura M.
      • Shigeno K.
      • Hyuga T.
      • Yoneda T.
      • Shiina H.
      • Igawa M.
      Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study.
      ,
      • Xu G.
      • Feng L.
      • Yao M.
      • Wu J.
      • Guo L.
      • Yao X.
      • Zhao L.
      • Xu H.
      • Wu R.
      A new 5-grading score in the diagnosis of prostate cancer with real-time elastography.
      ). LoE: 1C, GoR: B; 100% consensus agreement.

      Cancer detection in repeat biopsy

      SB is the standard technique for PCA detection, although 20% to 30% of clinically significant PCAs are still missed in the first set of biopsies. Therefore, clinicians always face a dilemma when patients have an elevated PSA level and negative biopsy results. This leads to repeat biopsies in approximately 38% of patients within 5 y, with an additional cancer detected in 13%–41% of patients. The PCA detection rate by SB decreases to 4%–10% in the third and fourth attempts mainly because of the heterogeneity of pathologic components, multifocal growth and cancers located in the anterior area that are hard to sample.
      • Salomon G.
      • Drews N.
      • Autier P.
      • Beckmann A.
      • Heinzer H.
      • Hansen J.
      • Michl U.
      • Schlomm T.
      • Haese A.
      • Steuber T.
      • Graefen M.
      • Becker A.
      Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.
      , in a large cohort of 1024 consecutive patients, reported a relative increase in the detection rate of 24.8% in patients undergoing re-biopsy, adding four additional SE-targeted biopsies to the randomized biopsy scheme. It must be noted that the targeted biopsies in this cohort of men missed a high proportion of tumors detected by the SB, and therefore SE-targeted biopsies were considered as an addition to randomized biopsies (
      • Salomon G.
      • Drews N.
      • Autier P.
      • Beckmann A.
      • Heinzer H.
      • Hansen J.
      • Michl U.
      • Schlomm T.
      • Haese A.
      • Steuber T.
      • Graefen M.
      • Becker A.
      Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.
      ). The false-negative rate of prostate biopsy is 17%–21% in patients with negative first biopsies (
      • Mian B.M.
      • Naya Y.
      • Okihara K.
      • Vakar-Lopez F.
      • Troncoso P.
      • Babaian R.J.
      Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy.
      ,
      • Singh H.
      • Canto E.I.
      • Shariat S.F.
      • Kadmon D.
      • Miles B.J.
      • Wheeler T.M.
      • Slawin K.M.
      Predictors of prostate cancer after initial negative systematic 12 core biopsy.
      ).
      MRI/TRUS fusion-guided biopsy has proven capable of detecting PCA in different settings, and the addition of SE increases the detection rate of prostate biopsies. Some authors have investigated the value of adding SE to MRI/TRUS fusion in patients with previous negative biopsies. Targeted biopsies under guidance of SE in combination with MRI/TRUS fusion detect cancer in 26.4% and increase the overall detection rate to 43% when combined with the systematic approach, whereas SB detected cancers in 38% of patients. Targeted biopsy with SE and MRI/TRUS fusion detects more clinically significant cancers than SB (90.6% vs. 73.9%). In addition, targeted biopsy achieved higher detection rates per core compared with SB (14.7% vs. 6.5%). The sensitivity and specificity of MRI/SE fusion are 77.8% and 77.3% versus 74.1% and 62.9% for MRI. The majority (90.6%) of cancers found by the targeted approach are clinically significant, whereas only 75% of those found by SB are significant cancers. Cases of Gleason ≥8 were only detected via targeted biopsies identified on MRI and/or SE (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ). Nearly 25% of cases would have been misdiagnosed if only a targeted biopsy or SB had been performed. As to the biopsy results per core, the mean rate of cancer infiltration per core is significantly higher in targeted biopsy cores (40.8%) compared with SB cores (21.3%). MRI/TRUS fusion with biopsy of both the SE and mpMRI abnormalities seems to increase the detection of clinically significant cancers and cancers located in the anterior gland in a repeat-biopsy setting. Targeted fusion biopsy is comparable to saturation biopsy in terms of PCA detection rates while requiring fewer biopsy cores (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ).
      Recommendation 17. The addition of SE of the prostate can increase the PCA detection rate in patients undergoing repeat biopsy (
      • Salomon G.
      • Kollerman J.
      • Thederan I.
      • Chun F.K.
      • Budaus L.
      • Schlomm T.
      • Isbarn H.
      • Heinzer H.
      • Huland H.
      • Graefen M.
      Evaluation of prostate cancer detection with ultrasound real-time elastography: A comparison with step section pathological analysis after radical prostatectomy.
      ). LoE: 1C, GoR: B; 100% consensus agreement.
      Recommendation 18. SE-targeted biopsies should always be performed in addition to standard systematic biopsies (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ,
      • Mian B.M.
      • Naya Y.
      • Okihara K.
      • Vakar-Lopez F.
      • Troncoso P.
      • Babaian R.J.
      Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy.
      ,
      • Singh H.
      • Canto E.I.
      • Shariat S.F.
      • Kadmon D.
      • Miles B.J.
      • Wheeler T.M.
      • Slawin K.M.
      Predictors of prostate cancer after initial negative systematic 12 core biopsy.
      ). LoE: 1B, GoR: B; 100% consensus agreement.

      Local staging

      In the current literature, SE's ability to predict ECE has conflicting results:
      • Brock M.
      • von Bodman C.
      • Sommerer F.
      • Loppenberg B.
      • Klein T.
      • Deix T.
      • Palisaar J.R.
      • Noldus J.
      • Eggert T.
      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.
      report a sensitivity and specificity for SE of 38% and 96%, respectively, which represents an improvement in comparison to gray-scale TRUS but still remains inadequate in clinical settings. In contrast, a sensitivity of 79% and specificity of 89% for the detection of ECE were revealed by SE (
      • Pelzer A.E.
      • Heinzelbecker J.
      • Weiss C.
      • Fruhbauer D.
      • Weidner A.M.
      • Kirchner M.
      • Stroebel P.
      • Schoenberg S.O.
      • Dinter D.J.
      Real-time sonoelastography compared to magnetic resonance imaging using four different modalities at 3.0 T in the detection of prostate cancer: Strength and weaknesses.
      ). A sensitivity for PCA detection confined to the capsule of 51.6% and of 79.3% was revealed by ECE (
      • Zhu Y.
      • Chen Y.
      • Qi T.
      • Jiang J.
      • Qi J.
      • Yu Y.
      • Yao X.
      • Guan W.
      Prostate cancer detection with real-time elastography using a bi-plane transducer: Comparison with step section radical prostatectomy pathology.
      ). They stated that this might be related to the fact that tumors with larger diameters, which were more likely to be detected by SE, were more likely to extend throughout the capsule (
      • Zhu Y.
      • Chen Y.
      • Qi T.
      • Jiang J.
      • Qi J.
      • Yu Y.
      • Yao X.
      • Guan W.
      Prostate cancer detection with real-time elastography using a bi-plane transducer: Comparison with step section radical prostatectomy pathology.
      ). Examples for staging are illustrated in Figure 5.
      Figure thumbnail gr5
      Fig. 5Examples of strain elastography (SE) of the prostate. (a) T1. (b) T2. (c) T3. (d) T4. (a) Seventy-two-year-old man with a prostate-specific antigen (PSA) level of 6.14 ng/mL. Transrectal ultrasound (left image) revealed a hypo-echoic lesion measuring 13 mm (arrows) in the peripheral zone in the left lobe of the gland. SE (right image) revealed a hard area (arrows) at the corresponding site. Pathologic examination after biopsy revealed the stiff area is prostate cancer; the remaining prostate exhibits bilateral diffuse PCA with a Gleason score of 3 + 4 = 7. Thus, the SE result is a true positive. (b) Fifty-nine-year-old man with a PSA level of 10.9 ng/mL. Transrectal ultrasound (left image) revealed a hypo-echoic lesion measuring 7 mm (arrows) in the left peripheral zone. SE (right image) revealed a stiff area (arrows) corresponding to the B-mode abnormality. Pathologic examination after biopsy revealed the stiff area is benign prostatic hypertrophy, whereas for the remaining prostate, bilateral diffuse prostate cancer with a Gleason score of 3 + 3 = 6 is found. Thus, the SE result is a false positive. (c) Fifty-nine-year-old man with a PSA level of 78 ng/mL. Transrectal ultrasound (left image) revealed no lesion in the gland. SE (right image) detected a stiff area (arrows) in the left peripheral zone. Pathologic examination after biopsy reveals bilateral diffuse prostate cancer with a Gleason score of 4 + 5 = 9. (d) Elastogram (right side) revealed a disrupted soft rim sign in a patient with a huge tumor in the right prostate gland suspicious for extracapsular extension of tumor. The corresponding B-mode image is on the left (
      • Junker D.
      • Schafer G.
      • Kobel C.
      • Kremser C.
      • Bektic J.
      • Jaschke W.
      • Aigner F.
      Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis.
      ,
      • Junker D.
      • Zordo D.
      • Quentin M.
      • Ladurner M.
      • Bektic J.
      • Horniger M.
      • Jaschke W.
      • Aigner F.
      Real-time elastography of the prostate.
      ).
      Recommendation 19. The addition of SE of the prostate can improve staging over that of TRUS alone (
      • Pelzer A.E.
      • Heinzelbecker J.
      • Weiss C.
      • Fruhbauer D.
      • Weidner A.M.
      • Kirchner M.
      • Stroebel P.
      • Schoenberg S.O.
      • Dinter D.J.
      Real-time sonoelastography compared to magnetic resonance imaging using four different modalities at 3.0 T in the detection of prostate cancer: Strength and weaknesses.
      ,
      • Zhu Y.
      • Chen Y.
      • Qi T.
      • Jiang J.
      • Qi J.
      • Yu Y.
      • Yao X.
      • Guan W.
      Prostate cancer detection with real-time elastography using a bi-plane transducer: Comparison with step section radical prostatectomy pathology.
      ). LoE: 2B, GoR: C; 78% consensus agreement.
      Recommendation 20. Although SE may detect capsular or extracapsular extension, SE of the prostate cannot exclude capsular or extracapsular extension (
      • Pelzer A.E.
      • Heinzelbecker J.
      • Weiss C.
      • Fruhbauer D.
      • Weidner A.M.
      • Kirchner M.
      • Stroebel P.
      • Schoenberg S.O.
      • Dinter D.J.
      Real-time sonoelastography compared to magnetic resonance imaging using four different modalities at 3.0 T in the detection of prostate cancer: Strength and weaknesses.
      ,
      • Zhu Y.
      • Chen Y.
      • Qi T.
      • Jiang J.
      • Qi J.
      • Yu Y.
      • Yao X.
      • Guan W.
      Prostate cancer detection with real-time elastography using a bi-plane transducer: Comparison with step section radical prostatectomy pathology.
      ). LoE: 5, GoR: D; 90% consensus agreement.

      Guiding prostate biopsy

      Improvement in biopsy guidance using SE has been reported (
      • Kapoor A.
      • Kapoor A.
      • Mahajan G.
      • Sidhu B.S.
      Real-time elastography in the detection of prostate cancer in patients with raised PSA level.
      ,
      • König K.
      • Scheipers U.
      • Pesavento A.
      • Lorenz A.
      • Ermert H.
      • Senge T.
      Initial experiences with real-time elastography guided biopsies of the prostate.
      ,
      • Walz J.
      • Marcy M.
      • Maubon T.
      • Brunelle S.
      • Laroche J.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Real time elastography in the diagnosis of prostate cancer: Comparison of preoperative imaging and histology after radical prostatectomy.
      ,
      • Walz J.
      • Marcy M.
      • Pianna J.T.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Bladou F.
      Identification of the prostate cancer index lesion by real-time elastography: Considerations for focal therapy of prostate cancer.
      ), but some well-designed studies did not confirm these results (
      • Wang R.
      • Chen J.J.
      • Hu B.
      Transrectal real-time elastography-guided transperineal prostate biopsy as an improved tool for prostate cancer diagnosis.
      ). In a randomized prospective study (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ), there was a significantly higher PCA detection rate in the SE group than in the control group (51.1% vs. 39.4%). Overall the sensitivity and specificity of PCA detection were 60.8% and 68.4%, respectively, for the SE-targeted approach. In other studies comparing five-core SE targeted biopsy with 10-core SB, the PCA detection rate per patient for the targeted approach was comparable to that for the systemic approach (21.3%–30 % vs. 19.1%–25%), but an SE targeted core was 2.9- to 4.7-fold more likely to be cancer positive than a systemic core (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ).
      In addition, nearly all studies have indicated that the SE-targeted approach detects high-risk PCA more reliably than SB, requires a reduced number of cores for PCA detection and enhances the overall sensitivity in the combined biopsy setting. Through the improved visualization of tumors, SE may lead to more targeted biopsies in the future and reduce the number of random biopsy cores required to diagnose PCA. Future studies are needed to exclude a systematic biopsy in addition to targeted biopsies. This makes it attractive for patients who are interested in a smaller number of biopsies with less morbidity, but without the risk that relevant cancers are missed (
      • Dudea S.
      • Giurgiu C.
      • Dumitriu D.
      • Chiorean A.
      • Ciurea A.
      • Botar-Jid C.
      • Coman I.
      Value of ultrasound elastography in the diagnosis and management of prostate carcinoma.
      ,
      • Giurgiu C.
      • Manea C.
      • Crisan N.
      • Bungardean C.
      • Coman I.
      • Dudea S.
      Real-time sonoelastography in the diagnosis of prostate cancer.
      ).
      SE-targeted biopsy should be used in combination with SB; PCA detection rates of the combined approach, 10-core SB and 4-core SE biopsy were 46.2%, 39.1% and 29.0%, respectively (
      • Salomon G.
      • Drews N.
      • Autier P.
      • Beckmann A.
      • Heinzer H.
      • Hansen J.
      • Michl U.
      • Schlomm T.
      • Haese A.
      • Steuber T.
      • Graefen M.
      • Becker A.
      Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.
      ). SE-targeted biopsy might be useful in detecting patients with PCA not detected by systematic 10-core biopsy. The additional use of SE is reported to lead to an incremental detection rate of 18.3% to 24.8% for a primary or re-biopsy session. Targeted biopsy under SE guidance seems to have the advantage in detecting significant PCA in that some significant PCAs are diagnosed only by SE biopsy (
      • Brock M.
      • Loppenberg B.
      • Roghmann F.
      • Pelzer A.
      • Dickmann M.
      • Becker W.
      • Martin-Seidel P.
      • Sommerer F.
      • Schenk L.
      • Palisaar R.
      • Noldus J.
      • Bodman C.
      Impact of real-time elastography on magnetic resonance imaging/ultrasound fusion guided biopsy in patients with prior negative prostate biopsies.
      ,
      • Brock M.
      • Roghmann F.
      • Sonntag C.
      • Sommerer F.
      • Tian Z.
      • Loppenberg B.
      • Palisaar R.J.
      • Noldus J.
      • Hanske J.
      • von Bodman C.
      Fusion of magnetic resonance imaging and real-time elastography to visualize prostate cancer: A prospective analysis using whole mount sections after radical prostatectomy.
      ). A positive SE might be an independent marker of the detection of high-risk PCA, and a negative SE argues against such a diagnosis (
      • Nygard Y.
      • Haukaas S.A.
      • Halvorsen O.J.
      • Gravdal K.
      • Frugard J.
      • Akslen L.A.
      • Beisland C.
      A positive real-time elastography is an independent marker for detection of high-risk prostate cancers in the primary biopsy setting.
      ). The addition of SE targeted cores to standard SB raises the negative predictive value from 79% to 97% for high-risk PCA. SE-targeted biopsy alone is not recommended because this approach missed a high proportion of patients with PCA in many studies (
      • Nygard Y.
      • Haukaas S.A.
      • Halvorsen O.J.
      • Gravdal K.
      • Frugard J.
      • Akslen L.A.
      • Beisland C.
      A positive real-time elastography is an independent marker for detection of high-risk prostate cancers in the primary biopsy setting.
      ,
      • Salomon G.
      • Drews N.
      • Autier P.
      • Beckmann A.
      • Heinzer H.
      • Hansen J.
      • Michl U.
      • Schlomm T.
      • Haese A.
      • Steuber T.
      • Graefen M.
      • Becker A.
      Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients.
      ,
      • van Hove A.
      • Savoie P.H.
      • Maurin C.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Walz J.
      Comparison of image-guided targeted biopsies versus systematic randomized biopsies in the detection of prostate cancer: A systematic literature review of well-designed studies.
      ).
      Recommendation 21. The addition of SE of the prostate can improve lesion localization for imaging-guided prostate biopsy. LoE: 2B, GoR: C; 100% consensus agreement.

      Comparison between SE and other imaging

      SE versus MRI

      It is of great interest to compare SE with mpMRI for PCA diagnosis, as mpMRI combining T2-weighted imaging and functional sequences is a very promising imaging technique for the detection and characterization of PCA. It has increasingly been used to evaluate the prostate (
      • Lim H.K.
      • Kim J.K.
      • Kim K.A.
      • Cho K.S.
      Prostate cancer: Apparent diffusion coefficient map with T2-weighted images for detection: A multireader study.
      ).
      The detection rates for SE and mpMRI are comparable with expert SE operators. Using a biopsy specimen as the reference standard (
      • Aigner F.
      • Pallwein L.
      • Junker D.
      • Schafer G.
      • Mikuz G.
      • Pedross F.
      • Mitterberger M.J.
      • Jaschke W.
      • Halpern E.J.
      • Frauscher F.
      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.
      ), SE showed a sensitivity rate and negative predictive value per patient of 84.6% and 86.7%, respectively, 84.6% and 83.3% for T2-weighted image MRI. On the other hand, using whole-mount pathology sections as the reference standard, a study found that SE detection rates were superior to those of MRI (74.1% vs. 47.4%) and nearly equal detection rates for SE alone on both the anterior (75.0%) and the posterior parts (73.7%) of the prostate (
      • Sumura M.
      • Shigeno K.
      • Hyuga T.
      • Yoneda T.
      • Shiina H.
      • Igawa M.
      Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study.
      ).
      SE showed advantages in the apex and midportions of the prostate for PCA detection, whereas mpMRI provided advantages in the base and TZ. Both SE and mpMRI have limitations, particularly in basal and anterior parts. Furthermore, most undetected tumors have a low tumor volume and Gleason score (
      • Pelzer A.E.
      • Heinzelbecker J.
      • Weiss C.
      • Fruhbauer D.
      • Weidner A.M.
      • Kirchner M.
      • Stroebel P.
      • Schoenberg S.O.
      • Dinter D.J.
      Real-time sonoelastography compared to magnetic resonance imaging using four different modalities at 3.0 T in the detection of prostate cancer: Strength and weaknesses.
      ). In a fused MRI with SE study to evaluate the prostates of 45 patients with histologically confirmed cancer, MRI. They found that MRI was more useful in the anterior gland, whereas SE was more useful in the posterior and apical parts, resulting in additional value in terms of sensitivity and specificity (58%–66% and 61%–75% respectively) (Brock et al. 2014).
      In 61 cancer lesions ≥0.2 cm3, SE detected 78% of cancer lesions in the PZ and 18.2% in the TZ, whereas mpMRI detected 90% and 72.2%, respectively (
      • Junker D.
      • Schafer G.
      • Kobel C.
      • Kremser C.
      • Bektic J.
      • Jaschke W.
      • Aigner F.
      Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis.
      ,
      • Junker D.
      • Zordo D.
      • Quentin M.
      • Ladurner M.
      • Bektic J.
      • Horniger M.
      • Jaschke W.
      • Aigner F.
      Real-time elastography of the prostate.
      ). Significant differences between the modalities were found for the TZ and anterior parts in prostates with a volume >40 mL. Detection rates for high-risk PCA (Gleason score ≥4 + 3) and cancer lesions with volumes >0.5 cm3 were 93.8% and 80.5%, respectively, for SE and 87.5% and 92.7%, respectively, for mpMRI. It could be concluded that SE and mpMRI detected high-risk PCA with high sensitivity, but mpMRI seems to have advantages in tumor volume assessment and in the detection of PCA in the TZ and in the anterior PCA within large prostate glands (>40 mL).
      Recommendation 22. There is insufficient evidence to make a recommendation regarding SE (accuracy, complementary techniques) in comparison to mpMRI at this time. LoE: 5, GoR: D; 100% consensus agreement.

      Strain elastography versus shear wave elastography

      No study has compared the SE and SWE techniques. SWE does, however, appear easier to perform and requires less training because manual compression is not required, and SWE is less subject to operator variability. However, it is essential for operators to experience and know the limitations of both techniques.
      Recommendation 23. There is insufficient literature to recommend SE versus SWE or vice versa. LoE: 5, GoR: D; 100% consensus agreement.

      Limitations

      The major limitations of SE are the lack of uniform compression over the entire gland, intra- and inter-operator dependency and penetration in large prostate glands (
      • Correas J.M.
      • Drakonakis E.
      • Isidori A.M.
      • Helenon O.
      • Pozza C.
      • Cantisani V.
      • Di Leo N.
      • Maghella F.
      • Rubini A.
      • Drudi F.M.
      • D'Ambrosio F.
      Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Khoury G.
      • Eiss D.
      • Helenon O.
      Ultrasound elastography of the prostate: state of the art.
      ). Compressibility of local tissue regions always depends on the surrounding tissue and the applied compression force. Intra- and inter-operator variability is dependent on the training level of the person performing the examination. Penetration issues in large prostate glands leads to poor SE image quality. Artifacts caused by slippage of the compression plane can occur in up to 32% of the images. This artifact is reduced with training and balloon interposition (
      • Tsutsumi M.
      • Miyagawa T.
      • Matsumura T.
      • Endo T.
      • Kandori S.
      • Shimokama T.
      • Ishikawa S.
      Real-time balloon inflation elastography for prostate cancer detection and initial evaluation of clinicopathologic analysis.
      ). Finally, there is an intrinsic limitation for all SE techniques—that is, not all cancers are stiff, and all stiff lesions are not cancerous (calcifications, fibrosis, etc.) (
      • Correas J.M.
      • Drakonakis E.
      • Isidori A.M.
      • Helenon O.
      • Pozza C.
      • Cantisani V.
      • Di Leo N.
      • Maghella F.
      • Rubini A.
      • Drudi F.M.
      • D'Ambrosio F.
      Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Khoury G.
      • Eiss D.
      • Helenon O.
      Ultrasound elastography of the prostate: state of the art.
      ). Elasticity information must always be combined with the results of the transrectal US B-mode and with the results of other imaging techniques, such as mpMRI. Images of false-positive findings with calcifications and penetration problems are provided in Figure 6.
      Figure thumbnail gr6
      Fig. 6False-positive strain elastography images caused by (a) calcifications and (b) application of inadequate stress. (a) Note the calcifications in the B-mode image on the left (red arrow). On the corresponding strain elastogram the area of calcifications is color coded blue, being very stiff (red arrow). (b). Strain elastogram of a prostate gland with a color map, on which blue is stiff and red is soft. Note there is no color coding in the right portion of the gland (arrow). This is due to uneven stress applied to the prostate gland with the transrectal transducer. There was insufficient stress in this area to produce a measureable strain.
      (a) Image courtesy of Dr. Masakazu Tsutsumi. (b) Image courtesy of Dr. Jean-Michel Correas.
      Recommendation 24. The presence of calcifications can cause false-positive results (
      • Correas J.M.
      • Drakonakis E.
      • Isidori A.M.
      • Helenon O.
      • Pozza C.
      • Cantisani V.
      • Di Leo N.
      • Maghella F.
      • Rubini A.
      • Drudi F.M.
      • D'Ambrosio F.
      Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Khoury G.
      • Eiss D.
      • Helenon O.
      Ultrasound elastography of the prostate: state of the art.
      ). LoE: 4, GoR: C; 100% consensus agreement.

      Summary

      Transrectal US SE provides additional stiffness information for characterizing, detecting and locating PCA. It is also useful for guiding biopsies and staging PCA. SE should become an additional tool for prostate examination to complement traditional transrectal US and MRI. However, this technique has a considerable learning curve, and the limitations of SE should be kept in mind to achieve a correct diagnosis.

      Shear Wave Elastography

      Shear wave elastography does not require compression/release on the rectal wall to produce elastograms as required in SE. This technique is based on measurement of shear wave speed propagating through the tissues (
      • Bercoff J.
      • Tanter M.
      • Fink M.
      Supersonic shear imaging: a new technique for soft tissue elasticity mapping.
      ). It is a multi-wave imaging technique as it combines two different waves: the first, the shear wave, generated by an acoustic radiation force impulse, and a second, the ultrasonic wave, which captures the propagation of the shear wave. The speed of the shear wave is linked to the stiffness properties of the medium in which it propagates. Shear wave elastography provides a dynamic quantitative map of soft tissue visco-elastic properties in near real time. The basic principle underlying SWE relies on two successive steps: First, a shear wave is remotely induced by the endocavity probe through the rectal wall in the prostate using the acoustic radiation force of a focused ultrasonic beam; and second, the shear wave propagation is captured by imaging the prostate with the endocavity probe. The shear modulus (i.e., stiffness) is derived by measuring the shear wave propagation speed. The shear wave speed (in m/s) or the Young's modulus (in kPa) is color-coded for each pixel and displayed as an overlay on the image in B-mode.
      All vendors color-code stiff tissues as red, whereas soft tissues are coded in blue, although adjusting the color scale can affect the color appearance of lesions. The elasticity values (mean, standard deviation, min and max) are then calculated for each selected ROI. The ratio between the mean values of two ROIs placed in a suspicious region and in the adjacent normal peripheral zone (stiffness ratio) can also be calculated (Fig. 7).
      Figure thumbnail gr7
      Fig. 7Prostate shear wave elastography allows quantitative measurements of tissue stiffness using regions of interest (ROIs). The mean stiffness value is displayed for each ROI, as are the minimal maximal and standard deviation values calculated. When two ROIs are used to compare stiffness, the SWE elasticity ratio is calculated. This is a true ratio between mean elasticity values. For prostate shear wave elastography, the typical scale of displayed elasticity values is set at 50 to 70 kPa. Note that the posterior periprostatic space is color coded in blue because of the minimal pressure of the endocavity transducer. The strain ratio can be calculated by placing two ROIs, one in the lesion or area of concern and the second in normal prostate. The system automatically calculates the strain ratio between the two ROIs. In this case the area in the transitional zone (solid circle) is 1.29 stiffer than the normal prostate (dotted circle).
      This technology only recently became available on endfire endocavity transducers, explaining the limited number of published articles. Quality index and criteria are under development to improve the reliability of stiffness measurements (Fig. 8). It is unknown if the thresholds between benign and malignant lesions are similar for different ultrasound systems with SWE technology.
      Figure thumbnail gr8
      Fig. 8Quality parameter for shear wave elastography. Two-dimensional shear wave elastogram of the prostate of a 56-year-old patient with a prostate-specific antigen level of 10. Biopsies were all positive on the left side of the prostate, ranging from 10 to 17 mm in size and with a Gleason score of 7 (3 + 4). Biopsies were all negative on the right side. In the ROI placed in the mid left peripheral zone, the mean stiffness value is 38.8 kPa. The quality index, SI (stability index), is 94%, confirming adequate shear waves for analysis. In general, a SI of >90% confirms satisfactory shear waves for analysis.
      Courtesy of Jean-Michel Correas.

      Procedure

      Prostate SWE is also conducted after a complete evaluation of the prostate using B-mode and color or power Doppler imaging, with the patient lying in the left lateral position. SWE mode is activated, and each suspicious focal lesion is analyzed, avoiding any pressure on the transducer. Optimized settings should include maximized penetration and appropriate elasticity scale (70–90 kPa). The entire gland can also be scanned to detect stiff areas in the transverse plane. The SWE box is enlarged to the maximum to cover as much of the gland as possible. The prostate is scanned from base to apex, and cine loops are stored. For each plane, the transducer is maintained in a steady position for 3 to 4 s until the signals stabilize. Hypo-echoic lesions coded stiff (red) are highly suspicious for malignancy. The digital cine loop can be reviewed, and the ROI can be positioned over suspicious areas detected on either B-mode or SWE, even during the review process. The elasticity values (mean, standard deviation, min and max) are then calculated for each ROI.
      Recommendation 25. SWE examinations should be performed with minimal preload (pre-compression), and the focal zone is set by the system based on the field-of-view box LoE: 5, GoR: D; 100% consensus agreement.*
      Recommendation 26. The shear wave speed can be displayed either in m/s or as Young's modulus in kPa; either can be used to report results. It is encouraged to list both. LoE: 5, GoR: D; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.
      Recommendation 27. An appropriate stabilization time (2–4 s) is needed in SWE to obtain an optimal image (
      • Barr R.G.
      Elastography in clinical practice.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ). LoE: 4, GoR: C; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.
      Recommendation 28. If the area of concern is at the side of the image, rotating the probe to have the field of view is more central on the lesion is helpful. LoE: 5, GoR: D; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.

      Image interpretation

      Normal SWE pattern

      In young patients without prostatic disorders, the peripheral and central zones are coded in blue with a very homogeneous pattern (with stiffness value ranging from 15 to 25 kPa), whereas the transitional zone exhibits stiffness below 30 kPa. With the development of benign prostate hyperplasia, the peripheral zone remains soft with very homogeneous color encoding in blue (soft tissue), whereas the transition zone becomes heterogeneous and hard (red color), with a heterogeneous color pattern and elasticity values ranging from 30 to 180 kPa (
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      ). Examples of SWE of the prostate are provided in Figure 9.
      Figure thumbnail gr9
      Fig. 9(a) Sixty-five-year-old male with a low prostate-specific antigen (PSA) level, but a firm left-sided nodule on digital rectal examination. B-Mode and power Doppler did not identify any abnormalities. Shear wave elastography (SWE) revealed a lesion with high stiffness (red circle ROI) in the left mid-peripheral zone with a mean stiffness of 108 kPa. On biopsy, this was confirmed to be a Gleason 6 carcinoma. (b) A patient referred for transrectal ultrasound because of an elevated PSA. On B-mode there was a hypo-echoic nodule (yellow arrow). On SWE, the nodule identified on B-mode had a normal stiffness value of 20 kPa. However, a focal area of increased stiffness of 75 kPa was identified on SWE (red arrow) that was normal on the B-mode image. The biopsy of the hypo-echoic lesion (yellow arrow) revealed benign prostate tissue, whereas the area of increased stiffness on SWE (red arrow) was a Gleason 7 prostate cancer. (c) Seventy-five-year-old patient with elevated PSA. Two prior sextant biopsies were negative. His PSA had increased since the last biopsy from 8 to 12.3 ng/mL. On SWE, the patient's entire peripheral zone had a normal stiffness value (23 kPa). Repeat sextant biopsy was negative. Further studies need to be performed to determine if a negative SWE of the peripheral zone could be used to limit the number of biopsy samples that need to be obtained. (d) Example of extracapsular extension of a prostate cancer (red arrows).

      Lesion characterization

      A lesion can be characterized by obtaining the mean stiffness value of the lesion. The ROI should be placed so that it includes only the lesion. The mean value of stiffness should be used to characterize the lesion. The SWE ratio can be calculated by comparing the mean stiffness of the lesion with the mean stiffness of normal prostate. Note that the ratios are different when m/s is used compared with kPa; this results from the square factor in the conversion between the two units. Cutoff values for stiffness value and strain ratios are discussed below.
      Recommendation 29. The stiffness value (in either m/s or kPa) can be used to characterize a lesion. The stiffness ratio to normal prostate tissue can also be used (
      • Barr R.G.
      Elastography in clinical practice.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ). LoE: 4, GoR: C; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.
      Recommendation 30. The ROI should encompass only the area of the stiff lesion or the area of interest (
      • Barr R.G.
      Elastography in clinical practice.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ). LoE: 4, GoR: D; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.
      Recommendation 31. The mean stiffness value in the ROI should be reported. Note: The ROI must be adequately placed (
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ). LoE: 4, GoR: D; 100% consensus agreement.
      Indicates a member of the panel did not have experience with that technique and refrained from voting.
      Recommendation 32. The PI-RADS lexicon terminology and lesion location should be used. LoE: 5, GoR: D; 100% consensus agreement.*

      Semi-quantification

      As SWE provides quantified results, semi-quantification methods should not be utilized.

      Reproducibility and learning curve

      SWE reproducibility has been reported in a single article and showed an excellent overall intra-observer reproducibility (intra-class correlation coefficient [ICC] = 0.876), with minimal impact of ROI location, prostate volume and clinical variables (ICC = 0.826–0.917) (
      • Woo S.
      • Kim S.Y.
      • Lee M.S.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography assessment in the prostate: An intraobserver reproducibility study.
      ). The real-time capability of SWE allows the whole gland to be swept and stiff foci that are not always displayed in the B-mode image to be detected. PCAs usually appear as stiffer areas than the surrounding tissue.
      Recommendation 33. Although it is generally accepted that there is a learning curve in the performance of SWE prostate imaging, no established standardized training procedure has been proposed. It is generally accepted that the learning curve for SWE is smaller than that for SE. LoE: 5, GoR: D; 100% consensus agreement.*
      Recommendation 34. The operator should be trained in prostate TRUS and transrectal US-guided biopsies and have adequate training and experience with the US machine and the specific SWE technique used. LoE: 5, GoR: D; 100% consensus agreement.*
      Recommendation 35. The overall intra-observer reproducibility of SWE of the prostate is good (
      • Woo S.
      • Kim S.Y.
      • Lee M.S.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography assessment in the prostate: An intraobserver reproducibility study.
      ). LoE: 3B, GoR: C; 100% consensus agreement.*

      Review of the literature

      Several different applications of SWE of the prostate have been reported, including (i) characterization of abnormal regions detected by B-mode US, color Doppler US and/or power Doppler US, or MRI/mpMRI; (ii) detection of lesions not seen with any imaging technique; (iii) staging of PCA; and (iv) biopsy targeting.
      Several studies access the value of both strain and SWE, as outlined in Table 1, Table 2, Table 3, Table 4. Three different applications can be identified: First, characterization of an abnormal area detected on B-mode imaging, color Doppler US or even previous MRI examination; second, detection of a lesion not seen with any previous imaging technique; and third, biopsy targeting. Prostate elastography requires specific training; the learning curve may be shorter than that for strain elastography, which requires the operator to learn how to apply stress with the transducer. Some of the discrepancies in the literature arise from the poorer performance of the earliest implementations; more up-to-date systems seem to be easier to use and to provide more consistent results. However, most US manufacturers are also developing SWE techniques and should be extending their use to endocavitary transducers.
      Characterization of prostatic lesions

      SWE diagnostic performance compared with that of systematic biopsies

      Table 2 summarizes the studies assessing the diagnostic performance of elastography compared with randomized biopsies. SWE is the more recently developed technique so less literature is available (Table 3). In all studies, shear wave values were statistically significantly higher in PCAs than in benign lesions (p < 0.002 in all studies). It is important to note that only one system has been evaluated thus far (Aixplorer system, SuperSonic Imagine, Aix en Provence, France). The values provided below may be different for other SWE technology implementations. Some have reported that the difference in Young's moduli between benign lesions were all statistically non-significant (
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      )—benign versus atypia (p = 0.818), benign versus acute inflammation (p = 0.606), benign versus chronic inflammation (p = 0.0509) and acute inflammation versus chronic inflammation (p = 0.096)—whereas others (
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      ) reported a significant difference between normal prostate tissue and chronic inflammation (p = 0.021). Two reported a statistically significant linear trend of SWE elasticity with Gleason scores (Spearman's rank correlation coefficient ρ = 0.343 [
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      ] and ρ = 0.282], both p < 0.001). In addition, aggressive PCAs exhibited statistically significantly higher tissue stiffness (p < 0.01 in all studies) than indolent PCAs in several studies (
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ,
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      ). One study reported false-positive or false-negative results in the anterior and transition zones of the prostate gland (
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      ). In the largest study (
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ), including 184 patients, sensitivity, specificity and positive and negative predictive values were 97%, 70%, 70% and 97%, respectively, for a 35-kPa cutoff for diagnosing PCA with Gleason scores ≥6. This threshold is very similar to that reported by
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      (37 kPa); however, it is lower than those found by others (
      • Ahmad S.
      • Cao R.
      • Varghese T.
      • Bidaut L.
      • Nabi G.
      Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer.
      ,
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      ,
      • Woo S.
      • Kim S.Y.
      • Cho J.Y.
      • Kim S.H.
      Shear wave elastography for detection of prostate cancer: A preliminary study.
      ) (70, 43 and 50 kPa, respectively). In these latter studies, Gleason score 6 lesions were considered as non-cancerous in the statistical analysis. This also explains why overall malignant and benign tissue mean elasticity values were higher in
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      than in other studies (
      • Barr R.G.
      • Memo R.
      • Schaub C.R.
      Shear wave ultrasound elastography of the prostate: Initial results.
      ,
      • Correas J.M.
      • Tissier A.M.
      • Khairoune A.
      • Vassiliu V.
      • Mejean A.
      • Helenon O.
      • Memo R.
      • Barr R.G.
      Prostate cancer: Diagnostic performance of real-time shear-wave elastography.
      ) (Table 3).

      Elastography-targeted biopsy diagnostic rate compared with that of systematic biopsies

      The clinical utility of elastography targeted biopsies has been widely studied in recent years (Table 4). To assess the performance of elastography targeted biopsies, most studies compare the current standard of systematic 10- to 12-core biopsies with imaging targeted biopsies and/or with the combination of systematic and imaging targeted biopsies. When looking at the overall diagnostic rate (DR), all studies reported an increase over the systematic biopsy scheme, when systematic and targeted biopsies were combined. Only one study (
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      ) was performed using SWE, and in that study, patients with suspicious SWE findings were at 6.4-fold higher risk of harboring a clinically significant PCA and SWE targeted biopsies increased the per-patient DR by 4%.
      All SWE-targeted and strain-targeted biopsy studies reported an increase in DR. However, most studies also reported that in a number of patients, clinically significant PCAs (
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.
      ,
      • Boehm K.
      • Salomon G.
      • Beyer B.
      • Schiffmann J.
      • Simonis K.
      • Graefen M.
      • Budaeus L.
      Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols.
      ,
      • van Hove A.
      • Savoie P.H.
      • Maurin C.
      • Brunelle S.
      • Gravis G.
      • Salem N.
      • Walz J.
      Comparison of image-guided targeted biopsies versus systematic randomized biopsies in the detection of prostate cancer: A systematic literature review of well-designed studies.
      ) can be missed by performing only elastography targeted biopsies. Therefore, elastography-targeted biopsies should be performed in combination with systematic biopsies.

      SWE performance compared with whole-mount specimen after radical prostatectomy

      The capability of SWE to localize PCA lesions prior to radical prostatectomy was studied, and elasticity thresholds for detection of cancer foci were also assessed (
      • Boehm K.
      • Budaus L.
      • Tennstedt P.
      • Beyer B.
      • Schiffmann J.
      • Larcher A.
      • Simonis K.
      • Graefen M.
      • Beyersdorff D.
      • Salomon G.
      Prediction of significant prostate cancer at prostate biopsy and per core detection rate of targeted and systematic biopsies using real-time shear wave elastography.