european urology 54 (2008)

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1 european urology 54 (2008) available at journal homepage: Prostate Cancer Evaluation of Prostate Cancer Detection with Ultrasound Real-Time Elastography: A Comparison with Step Section Pathological Analysis after Radical Prostatectomy Georg Salomon a,c, *, Jens Köllerman b, Imke Thederan c, Felix K.H. Chun a, Lars Budäus c, Thorsten Schlomm c, Hendrik Isbarn c, Hans Heinzer a,c, Hartwig Huland a,c, Markus Graefen c a Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany b Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany c Martini Clinic, Prostate Cancer Center, Hamburg, Germany Article info Article history: Accepted February 28, 2008 Published online ahead of print on March 10, 2008 Keywords: Prostate cancer Detection Ultrasound Elastography Radical prostatectomy Pathological analysis Abstract Background: Conventional gray scale ultrasound has a low sensitivity and specificity for prostate cancer detection. Better imaging modalities are needed. Objective: To determine sensitivity and specificity for prostate cancer detection with ultrasound-based real-time elastography (elastography) in patients scheduled for radical prostatectomy (RP). Design, Setting, and Participants: Between July and October 2007, 109 patients with biopsy-proven localized prostate cancer (PCa) underwent elastography before RP. The investigator was blinded to clinical data. Measurements: A EUB-6500HV ultrasound system with a V53W 7.5 MHz end-fire transrectal probe was used preoperatively. Areas found to be suspicious for PCa were recorded for left and right side of the apex, mid-gland, and base. These findings were correlated with the obtained whole-mount sections after RP. Results and Limitations: Sensitivity and specificity for detecting PCa were 75.4% and 76.6%, respectively. A total of 439 suspicious areas in elastography were recorded, and 451 cancerous areas were found in the RP specimens. Positive predictive value, negative predictive value, and accuracy for elastography were 87.8%, 59%, and 76%, respectively. Nevertheless, there are limitations to our studies because we investigated specific patients scheduled for RP with apparent PCa. Whether elastography is practical as a diagnostic tool or can be used to target a biopsy and be at least as sensitive in tumor detection as extended biopsy schemes has yet to be determined. Conclusion: Elastography can detect prostate cancer foci within the prostate with good accuracy and has potential to increase ultrasound-based PCa detection. Further studies need to be done to approve these data and to evaluate whether tumor detection can be increased by elastography-guided biopsies. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Martini Clinic, University Hospital Hamburg Eppendorf, Martinistrasse 52, Hamburg, Germany. Tel ; Fax: address: gsalomon@uke.uni-hamburg.de (G. Salomon) /$ see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 european urology 54 (2008) Introduction The use of prostate-specific antigen (PSA) as a diagnostic and screening tool has led to a significant rise in the number of patients undergoing prostate biopsy. However the specificity of the PSA test is low [1,2]. Furthermore, because of the intensive PSA testing, in recent years prostate tumors have become drastically reduced in size [3] and only a small portion of the prostate is sampled by biopsies. Hence repeat biopsies are often taken; these biopsies have a relatively poor negative predictive value (NPV) with a detection rate of less than 20% [4]. Conventional gray-scale ultrasound has a low sensitivity and specificity for prostate cancer (PCa) detection. It is useful to guide biopsies but insufficient as a screening tool. Thus, an improved imaging modality for PCa detection using targeted biopsies is needed. Ultrasound-based real-time elastography imaging is a new technique that visualizes the differences in tissue strain produced by freehand compression [5]. Using elastography, the investigator is able to discriminate hard from soft tissue regions within the prostate. The phenomenon is based on the fact that the back-scattered ultrasound signals undergo displacement if the tissue is slightly compressed or decompressed (ie, approximately 2%). Stiffer tissues show less displacement than normal soft tissues (Fig. 1a). For visualization, stiffness values are marked in different colors and are shown in real-time images (Fig. 1b). Following the hypothesis that solid tumors differ in their consistency compared with the adjacent normal tissue, elastography has been investigated as a novel tool for detecting PCa. Promising results have been recently reported in small cohorts [6 8]. The goal of this study was to assess the value of elastography for localizing PCa in a selected, larger cohort of patients scheduled for radical prostatectomy (RP) by comparing results of the elastogram with PCa foci in whole-mount sections. In addition it was of interest to see whether elastography is feasible in daily routine. 2. Patients and methods A prospective, single-institution, single-observer study was carried out. Between July and October 2007, a total of 109 consecutive patients with biopsy-proven PCa scheduled for open retropubic RP underwent elastography by a single investigator at the day of admission to the hospital. The investigator was blinded to all clinical data. B-mode and elastography findings of all patients were recorded for right and left side of the apex, mid-gland, and base. Areas found to Table 1 Description of study population and histopathological findings of the prostate specimen after RP (n = 109) Variable Finding Age (mean, yr) 64.4 PSA (range, ng/ml) 6.4 ( ) Clinical stage (n) pt2 64 (58.7%) pt2a 9 pt2c 55 pt3 43 (39.4%) pt3a 35 pt3b 8 Insignificant 2 (1.8%) Gleason sum (%) >7 8.3 RP, radical prostatectomy. be suspicious for PCa were marked in the elastogram recordings (Fig. 1b). Pictures and results were stored on an external hard drive, and the location and size of suspicious areas were archived in a database (Filemaker pro 5.5DV1; FileMaker, Inc) for further evaluation. Digital rectal examination (DRE) and standardized transrectal ultrasound (TRUS) was performed by a different investigator to reduce the risk of an investigation bias. All clinicopathological data are summarized in Table 1. An EUB-6500HV ultrasound system (Hitachi Medical, Kashiwa, Japan) with a V53W (Hitachi Medical, Kashiwa, Japan) 7.5-MHz transrectal end-fire probe was used in the elastography mode. Elastography was performed prior to B-mode evaluation. All ultrasound procedures were performed in a left lateral position. A combined autocorrelation method was used for evaluation of tissue strain [9]. Real-time elastography images were obtained in the transverse plane at up to 30 frames per second. The investigator manually induced slight compression and decompression of the prostate using the transrectal ultrasound probe. A visual indicator for compression displayed on the screen provided feedback of the appropriate speed and pressure to minimize interobserver variability (Fig. 1b). The tissue density was visualized in a color scale from blue (hardest areas with minimum strain) to red (softest areas with greatest strain, Fig. 1b). Cancer-suspicious areas were defined as reproducible blue (stiff) results. Examination time was approximately 7 10 min for each patient. For histopathological evaluation, the prostatectomy specimens were sliced in 3-mm sections, according to the Stanford protocol, and microscopically analyzed after hematoxylineosin staining. The pathologist was blinded to the elastography results. The localization and size of each tumor focus were documented for all step sections on large macro photographs (Fig. 1c). All data were stored in the database. A bivariate analysis was used to correlate the presence or absence of tumor in the histopathological results with the findings of the elastograms; SPSS, version 13 (SPSS Inc, Chicago, IL, USA) was used to perform the analysis.

3 1356 european urology 54 (2008) Fig. 1 (a) Illustrated explanation of elastography using a phantom model. For simulation of cancerous tissue, a phantom based on gelatin was used. The tissue surrounding the phantom tumor consisted of 10% gelatin, whereas the phantom tumor (the star) consisted of 30% gelatin. In conventional ultrasound the phantom tumor is slightly visible, whereas the elastography modus clearly demarcates the harder phantom tumor. (Photographs courtesy of Hitachi, Kashiwa, Japan.) (b) Elastogram of the mid-gland: Visible indicator on the right side of the video screen (*). The silhouette of the prostate is circled in black color. A dark blue area on the left side of the prostate (arrow) in the peripheral zone suspected to be cancerous tissue is visualized. On the right side of the prostate, a light blue area is visible, indicating stiffer tissue. (c) Step-section histopathological findings in a corresponding sector of the left mid-gland. Tumor focus is circuited. The corresponding area in the elastogram (b) is marked with an arrow. (d) Histopathological findings of the focus described in (c) shows a Gleason 3+3 prostate cancer. 3. Results Overall, 439 suspicious areas were documented for elastography compared with the 451 tumor foci documented by the pathologist. In histopathology the distribution of the tumors was most prominent for the apical region (40%), followed by the midgland (33%), and the base of the prostate (26%), without any significant differences between the sides of the gland. The results obtained by elastography did not differ significantly (Table 2, Fig. 2). The histopathological results are summarized in Table 1. The sensitivity and specificity of elastography in classifying tumors were 75.4% and 76.7% (range, % and %), respectively. The positive

4 european urology 54 (2008) Table 2 Number of tumor foci found in the histopathological evaluation, and number of suspicious areas in the elastogram for right and left side of apex, mid-gland, and base regions Tumor foci (histopathology) Elastography findings (suspicious) Right Left Overall Right Left Overall Apex 91 (20%) 92 (20%) 40% 81 (20%) 67 (17%) 37% Mid-gland 73 (16%) 76 (16%) 33% 66 (17%) 62 (16%) 33% Base 60 (13%) 59 (13%) 26% 61 (16%) 51 (13%) 29% Total Allocation for overall tumor foci in the radical prostatectomy specimen and suspicious elastography findings are given in percentage for each region. predictive value (PPV), NPV, and accuracy were 87.8%, 59%, and 76%, respectively (Table 3). Elastograms showed false-positive, true-positive (Fig. 3a and b), multifocal (Fig. 4a c), and even small cancerous lesions detected by elastography, in correlation with the histopathological finding (Fig. 5a and b). Elastographic findings correlated best with tumor lesions in the apical region, followed by the midgland and base region (Table 4). The detection rate increased with higher Gleason grade. Sensitivity for Gleason 6, 7, and > 7 were 74%, 78%, and 93% (Table 3). A size criterion of >5 mm for elastography findings showed a slightly increased specificity to 80%. Fig. 2 Distribution of tumors/suspicious areas found in histopathological evaluation ( ) and in the elastogram ( ) for each side. Table 3 Accuracy of elastography findings for sides and regions a of the prostate, and correlation with Gleason sum (=6, 7, and >7) Sensitivity Specificity Apex right 84.0% 78.0% Apex left 68.1% 72% Mid-gland right 80.8% 80.5% Mid-gland left 72.0% 78.8% Base right 75.0% 67.0% Base left 72.8% 84.0% Gleason sum 6 74% 78% 7 78% 80% >7 93% 93% a Values for regional findings are as follows: sensitivity: 75.4%; specificity: 76.7%; positive predictive value: 87.8%; negative predictive value: 59%, and accuracy: 76%. Fig. 3 (a and b) Two blue (stiff) areas on both sides of the prostate are visualized. Incorrectly classified area on the right side of the prostate (*) was revealed by histopathological evaluation to be false-positive. A tumor correctly assessed by elastogram and verified by histopathological evaluation as cancerous tissue is located contralaterally (**).

5 1358 european urology 54 (2008) Fig. 4 (a) Multifocal cancerous tissue. The elastogram shows a diffuse distribution of dark blue colored (stiff) zones. The suspicious areas are marked for size measurement. Histopathological findings of corresponding whole-mount section for right (b) and left (c) side of the elastogram findings. 4. Discussion To date there is no imaging modality for a routine use that can visualize cancerous foci in the prostate with certainty. Systematic, randomized ultrasound-guided biopsy is the gold standard for PCa detection, because sensitivity and specificity for visualization of PCa foci using gray-scale ultrasound is low. The correlation of a hypoechoic area to cancer falls short, with reported conformities between 17% and 57% [10]. Furthermore, it is suggested that a high proportion of carcinomas in the prostate appear isoechogenic in conventional ultrasound [11]. The consequence of a negative biopsy in patients with suspicions of PCa is to perform a repeat biopsy. The timing and number of biopsy series and number of biopsies taken per biopsy are controversial. The current trend is to use more extended biopsy schemes [12]. In 41% of patients with at least two negative TRUS-guided biopsy series, a PCa could have been detected by saturation biopsy [13]. The RP specimen showed a Gleason grade > 6 in 25% of these individuals. Interestingly, 25% of those cancer patients detected by saturation biopsy were non organ-confined. If detected earlier, therapy might have been administered in an organ-confined stage of the disease, decreasing the chance of a possible biochemical recurrence. Only 15.6% had an insignificant tumor, whereas detection might have led to overtreatment. An imaging method that provides real-time visualization and targeted biopsies of tumor foci could be helpful to optimize the number of biopsies or to decrease the number of repeat biopsies. Promising imaging modalities such as magnetic resonance imaging (MRI) can help in the detection of PCa. The sensitivity of MRI is comparable to and may exceed that of transrectal biopsy [14], but sensitivity in PCa detection by MRI varies enormously, from 37% to 96% [15]. Endorectal MRI in combination with magnetic resonance spectroscopy might improve accuracy of PCa detection and might be useful to guide and, therefore, limit the number of iterative biopsies [16]. The major drawback of all these methods, despite increasing accuracy, is that they are time- and cost-intensive, with only a limited possibility for simultaneous biopsies of suspicious areas. Improved imaging modalities for transrectal ultrasound seems to be more practical for application in a daily routine. Additional information of the functional and structural components of prostate tissue can be measured during TRUS. Functional information can be obtained by three-dimensional vascular sonography [17] or contrast-enhanced ultrasound [18]. Structural differences (ie, tissue stiffness) can be measured and visualized by elastography. Elastography is based on the fact that most cancerous tissue is stiffer than normal tissue. This difference can be measured and visualized in TRUS. Elastography is a noninvasive, ultrasound-based real-time

6 european urology 54 (2008) Fig. 5 (a) Elastogram of the midgland: Two areas (arrows) of stiff tissue suspected to be cancerous tissue are visualized in dark blue color in the peripheral zone on the right side of the prostate. These spots are marked for size measurement. (b) Two small tumor foci identified by elastography (a) are confirmed as cancerous tissue in the histopathological analysis. method; therefore, it might be an ideal completion to gray-scale ultrasound in the diagnosis of PCa. This study was performed to compare preoperative elastography findings with definitive histopathology. Patients scheduled for RP, therefore, are ideal candidates. The investigator has the ability to get a direct validation of his findings. Definitive histopathology findings can be compared to preoperative elastography results (Fig. 1b and c). The results were promising given that sensitivity of up to 84% and specificity of at least 67% for PCa detection were achieved (Table 3). The detection rate of PCa foci with elastography was best in the apical region, where approximately 90% of the tumors were detected, compared with 75% in the basal region. A reason for the discrepancy might be due to the anatomical structural composition of the apex. The size and the volume of the region being investigated increases from the base to the apex of the prostate. The sensitivity appears to be superior on the right side of the gland. All ultrasound Table 4 Literature review: Comparison of elastography detection rate of prostate cancer foci with histopathological findings in whole-mount sections Sensitivity (%) n Mean PSA ng/ml Pallwein et al [6] Sumara et al [7] Tsutsumi et al [8] Konig et al [19] a (404) b PSA, prostate-specific antigen. a The intention of the study of Konig et al was to evaluate the usefulness of elastography for biopsy guidance for prostate cancer detection. b Authors did not include mean PSA in the manuscript; therefore, the PSA range has been added to the table. investigations were performed in a left lateral position. Hypothetically, because of this position, the left side of the prostate might be more compressed than the right side, which might lead to changes in distension of tissue. In previous studies [6,19], a size criterion of >5 mm for positive elastography findings was described. Specificity was slightly increased with the criteria used in our study. Nevertheless, no significant criteria were found in the false-positive elastography findings. Sensitivity and specificity increased up to 93% with higher Gleason grade. These findings are confirmed by the results of Sumara et al [7] who reported a detection rate of 60%, 69% and 100% for Gleason scores 6, 7, and > 7. Interestingly, these findings are in contrast to the results of Tsutsumi et al [8]. They showed that the detection of lowgrade tumor was more accurate than that of highgrade tumors. Surprisingly, in every patient, despite two incidental carcinomas, at least one tumor focus was detected. Consequently, none of the significant PCa patients would have been overlooked by elastography. This result would implicate 100% sensitivity for diagnosis of PCa. One has to be aware, though, that all of the patients were PCa patients and that this result can be stated for only this specific patient population. The available data on elastography are limited to a few studies [6 8,19] (Table 2) and underline the obtained results in this study. In a study of Tsutsumi et al [8], 51 patients (mean PSA, 11.0 ng/ml) with PCa were analyzed on the basis of clinical pathological findings. In this cohort sensitivity of tumor ranged from 94% for anterior tumors to 76% and 57% for tumors of the middle and posterior regions, respectively.

7 1360 european urology 54 (2008) Initial experiences with elastography-guided biopsies of the prostate have been reported by Konig et al [19] in In 404 men (46.3%) with suspicious digital rectal examination and/or increased PSA (range, ng/ml), a systemic sextant biopsy was performed. Overall PCa was found in 37.4% of all patients, with 84.1% of those cancers detected by elastography-guided biopsies and 64.2% by conventional ultrasound-guided biopsies. In comparison with the study of Konig et al [19], our study was performed on patients scheduled for RP whose PCa was supposed to be in a curative stage according to preoperative Gleason score and PSA level. These specific patients were investigated consecutively; there were no selection criteria such as a high PSA or a positive digital rectal examination with high evidence of non organ-confined PCa. This is an important issue because the main question was to detect PCa in a curative stage. The data are very promising because there is a need for better visualization of PCa in ultrasound to aid in developing a targeted prostate biopsy scheme. A few questions can be answered by this study in a cohort of specific patients: (1) Elastography seems to have good overall sensitivity in predicting tumor foci within the prostate. (2) At least one tumor focus was identified in each prostate. (3) Elastography technique shows good reproducibility as shown by our results being confirmed by other studies. (4) The technique is easy to use, has a short learning curve, and can be incorporated into the routine examination. Nevertheless, there are limitations to our study because we investigated specific patients scheduled for RP with apparent PCa. Therefore, further studies need to be performed to calculate the accuracy of PCa detection. Furthermore, it has to be determined whether elastography-guided biopsies increase PCa detection with fewer biopsy cores compared with a standard or even an extended biopsy scheme 5. Conclusion Elastography seems to be a good tool to improve PCa detection in ultrasound investigations. At least one tumor focus has been identified in each patient. Whether elastography is practical as a diagnostic tool, or whether it can be used to develop a targeted biopsy scheme that is at least as sensitive in tumor detection as an extended biopsy scheme has yet to be determined. Author contributions: Georg Salomon had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Salomon, Graefen, Schlomm, Chun. Acquisition of data: Salomon, Schlomm, Huland, Heinzer, Graefen, Thederan, Isbarn, Budäus. Analysis and interpretation of data: Salomon, Köllermann. Drafting of the manuscript: Salomon. Critical revision of the manuscript for important intellectual content: Graefen, Salomon. Statistical analysis: Salomon. Obtaining funding: Not applicable. Administrative, technical, or material support: Not applicable. Supervision: Graefen, Huland, Heinzer. Other (specify): histopathological evaluation: Köllermann. Financial disclosures: None. Funding/Support and role of the sponsor: None. References [1] Levine MA, Ittman M, Melamed J, et al. Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer. J Urol 1998;159: [2] Roehl KA, Antenor JA, Catalona WJ. Serial biopsy results in prostate cancer screening study. J Urol 2002;167: [3] Derweesh IH, Kupelian PA, Zippe C, et al. Continuing trends in pathological stage migration in radical prostatectomy specimens. Urol Oncol 2004;22: [4] Shepherd D, Keetch DW, Humphrey PA, et al. Repeat biopsy strategy in men with isolated prostatic intraepithelial neoplasia on prostate needle biopsy. J Urol 1996;156: [5] Ophir J, Cespedes I, Ponnekanti H, et al. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging 1991;13: [6] Pallwein L, Mitterberger M, Struve P, et al. Real-time elastography for detecting prostate cancer: preliminary experience. BJU Int 2007;100:42 6. [7] Sumura M, Shigeno K, Hyuga T, et al. Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study. Int J Urol 2007;14: [8] Tsutsumi M, Miyagawa T, Matsumura T, et al. The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: clinicopathological analysis. Int J Clin Oncol 2007;12: [9] Shiina TDM, Bamber JC. Strain imaging using combined RF and envelope autocorrelation processing. Presented at the IEEE Ultrasonics Symp 1996; [10] Frauscher F, Klauser A, Berger AP, et al. The value of ultrasound (US) in the diagnosis of prostate cancer. Radiologe 2003;43: [11] Sibley RI, Sibley AF. Correlation of digital rectal examination, prostate specific antigen, and transrectal ultrasound in prostate carcinoma in African Americans. J Natl Med Assoc 1997;89:

8 european urology 54 (2008) [12] Scattoni V, Zlotta A, Montironi R, et al. Extended and saturation prostatic biopsy in the diagnosis and characterisation of prostate cancer: a critical analysis of the literature. Eur Urol 2007;52: [13] Walz J, Graefen M, Chun FK-H, et al. High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series. Eur Urol 2006;50: [14] Anastasiadis AG, Lichy MP, Nagele U, et al. MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies. Eur Urol 2006;50: [15] Kirkham APS, Emberton M, Allen C. How good is MRI at detecting and characterising cancer within the prostate? Eur Urol 2006;50: [16] Amsellem-Ouazana D, Younes P, Conquy S, et al. Negative prostatic biopsies in patients with a high risk of prostate cancer. Is the combination of endorectal MRI and magnetic resonance spectroscopy imaging (MRSI) a useful tool? A preliminary study. Eur Urol 2005;47: [17] Sauvain JL, Palascak P, Bourscheid D, et al. Value of power Doppler and 3D vascular sonography as a method for diagnosis and staging of prostate cancer. Eur Urol 2003; 44: [18] Linden RA, Trabulsi EJ, Forsberg F, et al. Contrast enhanced ultrasound flash replenishment method for directed prostate biopsies. J Urol 2007;178: [19] Konig K, Scheipers U, Pesavento A, et al. Initial experiences with real-time elastography guided biopsies of the prostate. J Urol 2005;174: Editorial Comment on: Evaluation of Prostate Cancer Detection with Ultrasound Real-Time Elastography: A Comparison with Step Section Pathological Analysis After Radical Prostatectomy Ilias Cagiannos Division of Urology, The University of Ottawa, The Ottawa Hospital, Ottawa, Canada icagiannos@ottawahospital.on.ca Needle biopsy remains the gold standard for the diagnosis of prostate cancer. Although transrectal ultrasound (TRUS) is an integral part of the biopsy to visualize the prostate and facilitate needle placement, that technique alone has had a very limited role in the detection of prostate cancer. Prostate cancer is most often seen as a hypoechoic area; however, up to 40% of cancers are isoechoic and hypoechoic areas are nonspecific and present in benign processes such as prostatitis and focal atrophy [1]. As a result, TRUS alone has poor test characteristics for diagnosing prostate cancer with a positive predictive value (PPV) of 52.7%, a negative predictive value (NPV) of 72%, and an accuracy of 67% in modern series [2]. Systematic biopsy of the prostate is therefore required. In an attempt to increase the accuracy of systematic biopsy, the original sextant technique has been modified to include a greater number of cores, by performing two additional lateral peripheral zone biopsies from the base and two more from the midgland in addition to routine sextant biopsy, Presti and coauthors were able to identify 96% of cancers [3]. Importantly, however, five of the eight missed cancers in this study were detected by lesion-directed biopsies, which indicates a role for imaging as a diagnostic and biopsy-enhancing tool. Additionally, even with these expanded biopsy techniques, sampling errors still remain common and many patients require repeat biopsy. In patients who have initial negative TRUS-guided prostate biopsy, prostate cancer is detected in 10% to 19% on the second repeat biopsy, 5% to 14% on the third repeat biopsy, and 4% to 11% on the fourth repeat biopsy [4]. Common strategies for decreasing false-negative rates have included increasing the number of biopsies even further as well as using free/total prostate-specific antigen (PSA), PSA density, and PSA transition zone density. There has also been a renewed focus on the utility of imaging. Color and power Doppler use reflected sound waves to evaluate blood flow through local vessels. Power Doppler in particular is more sensitive for smaller vessels [2]. Contrastenhanced TRUS using microbubble contrast agents has recently been reported to improve detection of tumor vascularity [5]. As higher blood flow is associated with tumor, these techniques can help to target prostate biopsies. Limitations of these novel approaches include the hypervascularity of benign prostatic hypertrophy (making transition zone cancers difficult to detect) and prostatitis, both of which can lead to false-positive results. In this issue of European Urology, Salomon and colleagues investigate ultrasound-based real-time elastography in a cohort of 109 patients undergoing radical prostatectomy (RP) [6]. Correlating suspicious elastography findings with the whole-mount RP specimen yielded location-specific 75.4% sensitivity, 76.7% specificity, 87.8% PPV, 59% NPV, and 76% overall accuracy. These results are superior to those obtained from conventional TRUS and suggest that elastographic visualization of tumors may enhance the accuracy of biopsy and reduce the need for subsequent biopsies. Furthermore, the improved visualization of tumors may lead to more

9 1362 european urology 54 (2008) targeted biopsies and reduce the number of biopsy cores that are required in a given biopsy session. The finding that elastography detected at least one tumor focus in every patient, implying 100% sensitivity for prostate cancer diagnosis, has potential implications for prostate cancer screening. It is important to note, however, that this study was performed in men with an established diagnosis of prostate cancer. Larger-scale prospective trials, comparing standard TRUS biopsy with elastography-enhanced TRUS biopsy and incorporating various biopsy schemes, are required in undiagnosed men in order to determine the true benefit of elastography and whether it has a role in prostate cancer detection and screening. References [1] Shinohara K, Wheeler TM, Scardino PT. The appearance of prostate cancer on transrectal ultrasonography: correlation of imaging and pathologic examinations. J Urol 1989;142: [2] Kuligowska E, Barish MA, Fenlon HM, et al. Predictors of prostate carcinoma: accuracy of grayscale and color Doppler US and serum markers. Radiology 2001;220: [3] Presti JR, Chang JJ, Bhargava V, et al. The optimal systematic biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial. J Urol 2000;163: [4] Djavan B, Ravery V, Zlotta A, et al. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol 2001;166: [5] Frauscher F, Klauser A, Halpern EJ, et al. Detection of prostate cancer with microbubble ultrasound contrast agent. Lancet 2001;357: [6] Salomon G, Kollerman J, Thederan I, et al. Evaluation of prostate cancer detection with ultrasound real-time elastography: a comparison with step section pathological analysis after radical prostatectomy. Eur Urol 2008;54: DOI: /j.eururo DOI of original article: /j.eururo