Article

Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the PRI-MUS (prostate risk identification using micro-ultrasound) protocol

Authors:
  • CHU de Québec - Université Laval
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Abstract

Purpose: Conventional ultrasound systems operate at 6-9 MHz and serve as standard of care for guiding prostate biopsies. We present a protocol using a novel high-resolution (29 MHz) transrectal prostate micro-ultrasound system. This protocol includes a scoring system to assess risk of prostatic carcinoma and enable real-time targeted biopsies. Method: The system (ExactVu™, Exact Imaging, Toronto, ON) is currently being used in a multi-site 2,000 patient randomized clinical trial. Cine loops of 400 biopsies from this trial were used to create the PRI-MUS™ protocol and risk scale. Validation was performed on an independent, pathology-blinded set of 100 cines. 3 of the 5 investigators performing this validation were familiar with micro-ultrasound but naïve to the PRI-MUS protocol and received only 1 hour of training. Results: Each increase in risk score demonstrated a 10.1% [95% CI 9.3 - 10.8%] increase in probability of clinically significant cancer. Risk score also increased with Gleason Sum and cancer length with slopes of 0.15 [0.09-0.21] and 0.58 [0.43-0.73], respectively. Sensitivity and specificity were 80% and 37% with area under the ROC curve of 60±2%. The protocol was more accurate in detection of high grade disease (GS >7), with a peak AUC of 74% (mean 66%). Conclusions: The new resolution of the micro-ultrasound platform, paired with the PRI-MUS protocol, shows promise for real-time visualization of suspicious lesions and targeting of biopsies. The protocol's improved performance in more significant disease is consistent with the field's focus on reducing insignificant diagnoses and detecting high risk disease early.

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... than conventional US, paving the way for further research [22]. Another pivotal paper on the topic was written by Ghai et al. in 2016. In this article, the authors proposed Prostate Risk Identification using MUS (PRI-MUS), a 5-point grading system to stratify the risk of malignant prostatic lesions according to MUS images. ...
... This risk score was based on the ability of MUS to identify the histological changes typically associated with PCa due to its high spatial resolution ( Figure 1). It is important to underline that the authors found that the PRI-MUS score was significantly increased by increasing the Gleason sum (severity of cancer) and the fraction of malignant tissue in the biopsy core (quantity of cancer) [23]. ...
... It is important to underline that every US technique, including MUS, is strictly operator-dependent. Only a few studies specify that operators had adequate training with MUS [23,27,31]; therefore, this could strongly influence the results found. The studies included in this review and their main results are summarized in Table 1. ...
Article
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Background and Objectives: Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods: We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results: MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79–0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83–1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa (p = 0.89) and in the detection of Grade Groups ≥ 2 (p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions: Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.
... Microultrasound (microUS) is a new imaging modality that operates at high frequency (29 MHz), with the resulting microUS images having a resolution of up to 70 mm [16]. Microultrasound uses the Prostate Risk Identification using microUS (PRI-MUS) protocol to characterize and target suspicious regions for PCa, similar to the Prostate Imaging Reporting and Data System (PIRADS) protocol for MRI [17]. The microUS procedure is nearly identical to the standard conventional TRUS, with the additional benefit of enhanced imaging resolution and visualization of suspicious tissue that enables real-time targeted biopsies. ...
... The microUS procedure is nearly identical to the standard conventional TRUS, with the additional benefit of enhanced imaging resolution and visualization of suspicious tissue that enables real-time targeted biopsies. The learning curve for microUS for operators already performing TRUS is expected to be short and is limited to simple technique issues and understanding of PRI-MUS characteristics [17]. The aims of the current study were to evaluate the effectiveness of microUS-guided biopsy in the detection of csPCa, defined as a Gleason score of 7, and to compare the diagnostic performance of MRI and microUS. ...
... The two urologists (G.L. and M.L.) performing biopsies were initially naïve to microUS and received a standardized online training program as well as hands-on training prior to the beginning of the study. The PRI-MUS grading system was used to assess the risk of PCa visualized under microUS and to locate targets in any prostatic region [17]. Images and video loops were saved during the biopsy procedure for a retrospective analysis. ...
Article
Background Multiparametric magnetic resonance imaging (MRI) represents the gold standard for the diagnosis of clinically significant prostate cancer (csPCa). The search for alternative diagnostic techniques is still ongoing. Objective To determine the accuracy of microultrasound (microUS) for the diagnosis of csPCa within prospectively collected cohort of patients with a suspicion of prostate cancer (PCa) according to MRI. Design, setting, and participants A total of 320 consecutive patients with at least one Prostate Imaging Reporting and Data System (PIRADS) ≥3 lesion according to MRI were prospectively enrolled. Intervention All patients received microUS before prostate biopsy using the ExactVu system; the Prostate Risk Identification using microUS (PRI-MUS) protocol was used to identify targets. The urologists were blinded to MRI results until after the microUS targeting was completed. All patients received both targeted (based on either microUS or MRI findings) and randomized biopsies. Outcome measurements and statistical analysis The sensitivity and specificity of microUS to determine the presence of csPCa (defined as at least one core with a Gleason score ≥7 PCa) were determined. Multivariable logistic regression analysis was fitted to determine the predictors of csPCa. Results and limitations Clinically significant PCa was diagnosed in 116 (36.3%) patients. The sensitivity and negative predictive value of microUS for csPCa diagnosis were 89.7% and 81.5%, while specificity and positive predictive value were 26.0% and 40.8%, respectively. A combination of microUS-targeted and randomized biopsies would allow diagnosing the same proportion of csPCa as that diagnosed by an approach combining MRI-targeted and randomized biopsies (n = 113; 97.4%), with only three (2.6%) csPCa cases diagnosed by a microUS-targeted and three (2.6%) by an MRI-targeted approach. In a logistic regression model, an increasing PRI-MUS score was an independent predictor of csPCa (p ≤ 0.005). The main limitation of the current study is represented by the fact that all patients had suspicious MRI. Conclusions Microultrasound is a promising imaging modality for targeted prostate biopsies. Our results suggest that a microUS-based biopsy strategy may be capable of diagnosing the great majority of cancers, while missing only few patients with csPCa. Patient summary According to our results, microultrasound (microUS) may represent an effective diagnostic alternative to magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, providing high sensitivity and a high negative predictive value. Further randomized studies are needed to confirm the potential role of microUS in the diagnostic pathway of patients with a suspicion of prostate cancer.
... The ultrasonographic appearance of these areas on micro-US were studied, and a 5-point scoring system for suspicious lesions was created, termed PRI-MUS TM (Prostate Risk Identification for Micro-UltraSound). 15 The PRI-MUS TM protocol was then used following the retraining hiatus by all investigators to score and target suspicious areas noted during TRUS-biopsy in patients randomized to the micro-US arm. ...
... Targets in the initial portion of the trial included areas that appeared hypoechoic and/or demonstrated gross capsular abnormalities, in both the micro-US and conv-US arms. In the first portion of the trial investigators were not given separate guidance on target identification using micro-US, despite the fact that micro-US's 300% increase in spatial resolution provides a very different view of prostate tissue, 15 as there was no image library from which to draw. Images and 5-second cine-loops were thus taken at the time of each biopsy needle and stored for subsequent image analysis. ...
... In the second portion of the trial, training was provided on the newly developed PRI-MUS™ protocol for micro-US target identification. 15 Investigators were subsequently instructed to target PRI-MUS 3, 4, and 5 areas F I G U R E 1 First-generation ExactVu micro-ultrasound system used in this study (on a 1-5 suspicion scale, with 5 being the most suspicious)-for examples see Figure 2. ...
Article
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Objectives: To study high-frequency 29 MHz transrectal side-fire micro-ultrasound (micro-US) for the detection of clinically significant prostate cancer (csPCa) on prostate biopsy, and validate an image interpretation protocol for micro-US imaging of the prostate. Materials and methods: A prospective randomized clinical trial was performed where 1676 men with indications for prostate biopsy and without known prostate cancer were randomized 1:1 to micro-US vs conventional end-fire ultrasound (conv-US) transrectal-guided prostate biopsy across five sites in North America. The trial was split into two phases, before and after training on a micro-US image interpretation protocol that was developed during the trial using data from the pre-training micro-US arm. Investigators received a standardized training program mid-trial, and the post-training micro-US data were used to examine the training effect. Results: Detection of csPCa (the primary outcome) was no better with the first-generation micro-US system than with conv-US in the overall population (34.6% vs 36.6%, respectively, P = .21). Data from the first portion of the trial were, however, used to develop an image interpretation protocol termed PRI-MUS in order to address the lack of understanding of the appearance of cancer under micro-US. Micro-US sensitivity in the post-training group improved to 60.8% from 24.6% (P < .01), while specificity decreased (from 84.2% to 63.2%). Detection of csPCa in the micro-US arm increased by 7% after training (32% to 39%, P < .03), but training instituted mid-trial did not affect the overall results of the comparison between arms. Conclusion: Micro-US provided no clear benefit over conv-US for the detection of csPCa at biopsy. However, it became evident during the trial that training and increasing experience with this novel technology improved the performance of this first-generation system.
... 11 In accordance with the PI-RADSÔ 2.1 protocol for mpMRI, 12 suspicious prostate lesions are identified in realtime via micro-ultrasound with the PRI-MUS protocol. 13 Data suggest that micro-ultrasoundeguided PB provides greater sensitivity in detecting clinically significant PCa than conventional TRUS-guided PB 14 and may even present comparable detection rates to mpMRI-targeted PB for clinically significant PCa cases. 15 In this scope, we generated a systematic review and meta-analysis aiming to assess the detection rate of micro-ultrasoundeguided PB compared to mpMRI-targeted PB for clinically significant and insignificant PCa diagnosis. ...
... Across all studies, suspicious lesions were defined as PI-RADS !3 12 and PRI-MUS !3. 13 In studies reporting the number of core samples per target, micro-ultrasoundeguided PB required fewer specimens than mpMRI-targeted PB. The operators performing micro-ultrasoundeguided PB received appropriate training and all mpMRIs were evaluated by a radiologist experienced in mpMRI. ...
... Advances in imaging technologies have led to the development of the first 29 MHz micro-ultrasound system. 45 The ExactVu TM platform is a fast and urologist-friendly imaging modality that provides easier lesion targeting than mpMRI-targeted PB. 13,46 Moreover, micro-ultrasound follows the standardized schemes of conventional TRUS and is more sensitive in detecting clinically significant PCa than conventional TRUS. 14 Nonetheless, it should be stressed that the diagnostic accuracy of micro-ultrasound is limited by large prostate volume and specific tumor location, such as the transitional zone, while the accuracy of mpMRI is independent to these factors. ...
Article
Purpose: Micro-ultrasound is a novel, high-resolution, ultrasound technology, aiming to improve prostate imaging and, consequently, the diagnostic accuracy of ultrasound-guided prostate biopsy (PB). Micro-ultrasound-guided PB may present comparable detection rates to, the standard of care, multiparametric magnetic resonance imaging (mpMRI)-targeted PB for the diagnosis of clinically significant prostate cancer (PCa). We aimed to compare the detection rate of micro-ultrasound versus mpMRI-targeted PB for PCa diagnosis. Materials and methods: We performed a systematic review and meta-analysis of diagnostic accuracy studies comparing micro-ultrasound-guided PB to mpMRI-targeted PB as a reference standard test (PROSPERO ID: CRD42020198326). Records were identified by searching in PubMed, Scopus and Cochrane Library databases, as well as in potential sources of grey literature until November 30th, 2020. Results: We included 18 studies in the qualitative and 13 in the quantitative synthesis. In the quantitative synthesis, 1125 participants received micro-ultrasound-guided, followed by mpMRI-targeted and systematic PB. Micro-ultrasound and mpMRI-targeted PBs displayed similar detection rates across all PCa grades. The pooled detection ratio for ISUP Grade Group (GG) ≥2 PCa was 1.05 (95%CI: 0.93-1.19, I2=0%), 1.25 (95%CI: 0.95-1.64, I2=0%) for GG ≥3 and 0.94 (95%CI: 0.73-1.22, I2=0%) for clinically insignificant (GG=1) PCa. The overall detection ratio for PCa was 0.99 (95%CI: 0.89-1.11, I2=0%). Conclusions: Micro-ultrasound-guided PB provides comparable detection rates for PCa diagnosis with the mpMRI-guided PB. Therefore, it could be considered as an attractive alternative to mpMRI-targeted PB. Nevertheless, high quality randomized trials are warranted to corroborate our findings.
... Hence, while transitioning from SB to TB enhanced our ability to detect clinically significant disease, novel strategies are needed to decrease overdiagnosis of non-csPCa [5]. Micro-ultrasound (mUS) is a new imaging technique relying on a high-frequency transducer which confers a 300% improvement in spatial resolution over conventional ultrasound (US) [6]. A grading system has been proposed to stratify mUS images according to the probability of detecting csPCa (Prostate Risk Identification using Microultrasound-PRI-MUS score) [6]. ...
... Micro-ultrasound (mUS) is a new imaging technique relying on a high-frequency transducer which confers a 300% improvement in spatial resolution over conventional ultrasound (US) [6]. A grading system has been proposed to stratify mUS images according to the probability of detecting csPCa (Prostate Risk Identification using Microultrasound-PRI-MUS score) [6]. Micro-ultrasound-guided biopsies have been described as a promising alternative to MRI-TB with comparable detection rates for csPCa [7]. ...
... When specified, all authors were using the ExactVu™ micro-ultrasound system (Exact Imaging, Makham, Canada), with a 29 MHz high resolution for the performance of mUS-guided biopsies and also for guiding MRI-TB, after a standardized training program from Exact Imaging. Micro-US lesions were documented according to the prostate risk identification for micro-US (PRI-MUS) protocol [6] and targeted independently of the mpMRI lesions. Lesions that scored ≥ 3 in PRI-MUS or PI-RADS were defined as targets. ...
Article
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Purpose: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. Methods: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. Results: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I2 = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I2 = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis. Conclusion: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa.
... Recently, ultra-high resolution TRUS probe has developed and provided a potential to image or biopsy a signifi-cant prostate cancer. Accordingly, it will be promising for improving lesion detection and sampling under the guidance[20][21][22]. Recently, much higher-resolution TRUS has been introduced to image and biopsy a prostate cancer. ...
... Recently, much higher-resolution TRUS has been introduced to image and biopsy a prostate cancer. Increasing resolution may lead to increasing more precise detection or biopsy of a PI-RADS 4 or 5 lesion[20,21,23] Systematic biopsy was frequently performed in our study even if PI-RADS 4 or 5 was all visible on TRUS. The lesion visibility was different each other. ...
Article
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Purpose Recently, new magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) techniques and imaging features of Prostate Imaging and Report and Data System (PI-RADS) 4 or 5 have been reported. The aim of this study was to validate the outcomes of new TRUS-guided biopsy techniques for cancer detection in patients with PI-RADS 4 or 5. Methods Between June 2018 and November 2018, 94 men underwent TRUS-guided biopsy after PI-RADS 4 (n=59) or 5 (n=35) was categorized as an index lesion on MRI. For PI-RADS 4 group, target biopsy was performed in 5 and combination biopsy (target and systematic biopsies) was in 54. For PI-RADS 5 group, target biopsy was performed in 19 and combination biopsy was in 16. Target to combination biopsy ratios and significant cancer detection rates (CDRs) were compared between the groups. Significant cancer was defined as a Gleason score ≥ 7 tumor. Standard reference was biopsy examination. Fisher’s exact were used for statistical analysis. Results Target to combination biopsy ratios was 5:54 in the PI-RADS 4 group and 19:16 in the PI-RADS 5 group (P
... The first results of a system using 21 MHz microultrasound (MUS) (from Exact Imaging, formerly Imagistx, Inc., Toronto, Canada) compared to standard TRUS were presented by Pavlovich et al. in 2014[25]. This system has been further improved, and a standardized protocol based on the 29 MHz ExactVue System, called prostate risk identification using microultrasound (PRI-MUS™), was established [26]. With a combination of high frequency ultrasound waves of 29MHz and a very high crystal densitiy a spatial resolution of 70 microns compared to around 300 microns on conventional TRUS is achieved [27]. ...
... In 2014, Pavlovich et al. first introduced a system with higher frequency which produced superior spatial resolution [25]. As a result alterations, as tracks of prior biopsies, that have not been visible before, can be detected (Fig. 1) To address the second point of contention of conventional TRUS, i.e. interreader variability, Ghai et al. created a scoring system for prostatic tissue named PRI-MUS [26]. The 5-point scoring from very likely benign to highly likely malignant (Fig 2) has since been validated in the studies described below. ...
Article
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Only a decade ago there were insufficient imaging options for the detection and local staging of prostate cancer. However, the introduction of multiparametric magnetic resonance imaging (mpMRI) has advanced a much-needed tool for this scope of application. The possibilities and limitations of mpMRI have been well studied. Imaging must be acquired and evaluated using a standardized protocol (the latest version of PI-RADS). Sensitivity has been shown to increase with higher grades and larger tumors and while the detection rate on a per patient basis is relatively high, the per-lesion detection rate is far inferior. Various specialists have attempted to elevate the use of transrectal ultrasound, a tool frequently used by all urologists. Encouragement for this idea comes from a recently introduced system of high frequency transrectal ultrasound. The level of evidence supporting its use in the detection and staging of prostate cancer is not comparable to mpMRI yet, but initial prospective studies indicate good potential. The sensitivity of microultrasound and mpMRI for clinically significant prostate cancer ranges from 94-100% and 88-90%, respectively. Further areas of application, such as local staging for prostate and bladder cancer, are currently being evaluated. In summary, microultrasound presents a promising technology for further improving urological imaging and allows for the possibility of returning prostate cancer imaging to urologists. This review will summarize the current scientific basis for the use of microultrasound in the detection of prostate cancer.
... Therefore all investigators performing microUS biopsy in this trial will be required to have completed at least stage 3 of 4 in this training program. Completion of the standardized training program may also provide improved interreader variability, which was initially found to be "fair to moderate" 30 . However examining the effect of this program on inter-reader variability is not a focus of this study. ...
... MicroUS biopsy will be performed on subjects who have not received mpMRI. The biopsy will include targeted sampling based on the PRI-MUS protocol 30 , with lesions of PRI-MUS 3-5 receiving 3 targeted samples each. As well, 12 systematic samples will be taken spread evenly throughout the gland. ...
Article
Background Micro-ultrasound (microUS) is a novel ultrasound-based imaging modality which has demonstrated the ability to visualize prostate cancer. Multiparametric MRI/ultrasound (mpMRI/US) fusion has recognized advantages for the performance of prostate biopsy, however, it encompasses additional cost, time and technical expertise to performing prostate biopsy in comparison to conventional trans-rectal ultrasound biopsy. MicroUS may simplify and optimize this pathway. Methods OPTIMUM is a 3-arm randomized controlled trial comparing microUS guided biopsy with MRI/US fusion and MRI/MicroUS “contour-less” fusion. This trial will investigate whether microUS alone, or in combination with mpMRI, provides effective guidance during prostate biopsy for the detection of clinically significant prostate cancer (csPCa) for biopsy naïve subjects. 1200 subjects will be randomized. The economic impact will be evaluated. Results The rate of csPCa (defined as Grade Group 2 and above) in each arm will be compared. The primary hypothesis is non-inferiority of csPCa rate between the MRI/US fusion arm and the microUS-only arm (including the blinded microUS-only portion of the MRI/MicroUS arm). As a secondary objective, the csPCa rate between MRI/MicroUS fusion and MRI/US fusion arms will also be compared. Other secondary objectives include the increase in rate of patients diagnosed with csPCa due to each type of sample (mpMRI targeted, microUS targeted, systematic), the negative predictive value of each imaging modality, and a health economic analysis of the procedures in each arm. Conclusions OPTIMUM will determine whether microUS can be used as an alternative to MRI/US fusion biopsy. The trial will also evaluate the efficacy of the simplified “contour-less” MRI/MicroUS fusion procedure. The adoption of the microUS technique will increase the proportion of men who can benefit from modern imaging-centric diagnostic strategies, and may help reduce variability, complexity, waiting time and cost within the diagnostic pathway.
... The Score ranges from 1-5, very low risk, some risk, intermediate-risk, significant risk, and very high risk. The authors agree that combining this protocol with multiparametric features can enhance the US power in diagnosing PCa, especially csPCa [66]. ...
Article
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Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer.
... Microultrasound is a new diagnostic tool that improves image resolution by use of high-frequency imaging (29 MHz) [82]. A 2020 report [83] showed that most MRI lesions are visible in real time on microultrasound. ...
Article
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Prostate cancer is the second most common malignancy in men worldwide. Systematic transrectal prostate biopsy is commonly used to obtain tissue to establish the diagnosis. However, in recent years, MRI-targeted biopsy (based on an MRI examination performed prior to consideration of biopsy) has been shown to detect more clinically significant cancer and less clinically insignificant cancer compared to systematic biopsy. This approach of performing MRI prior to biopsy has become, or is becoming, a standard of practice in centers throughout the world. This growing use of an MRI-directed pathway is leading to performance of a larger volume of MRI-targeted prostate biopsies. The three common MRI-targeted biopsy techniques are cognitive biopsy, MRI-ultrasound software fusion biopsy, and MRI in-bore guided biopsy. These techniques for using MRI information at the time of biopsy can be performed via a transrectal or transperineal approach. This narrative review presents the three MRI-targeted biopsy techniques along with their advantages and shortcomings. Comparisons among the techniques are summarized based on the available evidence. Studies to date have provided heterogeneous results, and the preferred technique remains debated.
... All lesions detected by microUS were classified according to Prostate Risk Identification Using Micro-Ultrasound (PRI-MUS) score [11]. The dominant suspicious lesion was defined as the lesion with the highest PRI-MUS score or, in case of multiple lesions with the same PRI-MUS score, as the largest. ...
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Purpose We aim to evaluate the accuracy of micro-ultrasound (microUS) in predicting extraprostatic extension (EPE) of Prostate Cancer (PCa) prior to surgery. Methods Patients with biopsy-proven PCa scheduled for robot-assisted radical prostatectomy (RARP) were prospectively recruited. The following MRI-derived microUS features were evaluated: capsular bulging, visible breach of the prostate capsule (visible extracapsular extension; ECE), presence of hypoechoic halo, and obliteration of the vesicle-prostatic angle. The ability of each feature to predict EPE was determined. Results Overall, data from 140 patients were examined. All predictors were associated with non-organ-confined disease (p < 0.001). Final pathology showed that 79 patients (56.4%) had a pT2 disease and 61 (43.3%) ≥ pT3. Rate of non-organ-confined disease increased from 44% in those individuals with only 1 predictor (OR 7.71) to 92.3% in those where 4 predictors (OR 72.00) were simultaneously observed. The multivariate logistic regression model including clinical parameters showed an area under the curve (AUC) of 82.3% as compared to an AUC of 87.6% for the model including both clinical and microUS parameters. Presence of ECE at microUS predicted EPE with a sensitivity of 72.1% and a specificity of 88%, a negative predictive value of 80.5% and positive predictive value of 83.0%, with an AUC of 80.4%. Conclusions MicroUS can accurately predict EPE at the final pathology report in patients scheduled for RARP.
... Emerging technologies and prostate cancer biomarkers are playing a vital role in prostate cancer diagnosis and treatment (33,34). Micro-ultrasound is a novel highresolution imaging technology for diagnosing prostate cancer which is complementary for mpMRI (35)(36)(37)(38). Compare to mpMRI, micro-ultrasound, which promises real-time visualization of suspicious lesions and targeting of biopsies, has shown same or superior sensitivity (37). ...
Article
Background: Seminal vesicle invasion (SVI) is considered to be one of most adverse prognostic findings in prostate cancer, affecting the biochemical progression-free survival and disease-specific survival. Multiparametric magnetic resonance imaging (mpMRI) has shown excellent specificity in diagnosis of SVI, but with poor sensitivity. The aim of this study is to create a model that includes the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score to predict postoperative SVI in patients without SVI on preoperative mpMRI. Methods: A total of 262 prostate cancer patients without SVI on preoperative mpMRI who underwent radical prostatectomy (RP) at our institution from January 2012 to July 2019 were enrolled retrospectively. The prostate-specific antigen levels in all patients were <10 ng/mL. Univariate and multivariate logistic regression analyses were used to assess factors associated with SVI, including the PI-RADS v2 score. A regression coefficient-based model was built for predicting SVI. The receiver operating characteristic curve was used to assess the performance of the model. Results: SVI was reported on the RP specimens in 30 patients (11.5%). The univariate and multivariate analyses revealed that biopsy Gleason grade group (GGG) and the PI-RADS v2 score were significant independent predictors of SVI (all P<0.05). The area under the curve of the model was 0.746 (P<0.001). The PI-RADS v2 score <4 and Gleason grade <8 yielded only a 1.8% incidence of SVI with a high negative predictive value of 98.2% (95% CI, 93.0-99.6%). Conclusions: The PI-RADS v2 score <4 in prostate cancer patients with prostate-specific antigen level <10 ng/mL is associated with a very low risk of SVI. A model based on biopsy Gleason grade and PI-RADS v2 score may help to predict SVI and serve as a tool for the urologists to make surgical plans.
... The exposure parameters (e.g. high frequency and low pressure amplitude) used in this manuscript are not typically used in clinical contrast-enhanced imaging or ultrasound therapy but may be applicable to some high frequency clinical 116,117 and pre-clinical applications 118 . Future manuscripts will focus on exposure parameters to explore specific imaging and therapeutic applications. ...
Article
A lipid coated bubble (LCB) oscillator is a very interesting non-smooth oscillator with many important applications ranging from industry and chemistry to medicine. However, due to the complex behavior of the coating intermixed with the nonlinear behavior of the bubble itself, the dynamics of the LCB are not well understood. In this work, lipid coated Definity microbubbles (MBs) were sonicated with 25 MHz 30 cycle pulses with pressure amplitudes between 70 kPa-300 kPa. Here, we report higher order subharmonics in the scattered signals of single MBs at low amplitude high frequency ultrasound excitations. Experimental observations reveal the generation of period 2, period 3, and two different period 4 oscillations at low excitation amplitudes. Despite the reduced damping of the uncoated bubble system, such enhanced nonlinear oscillations has not been observed and can not be theoretically explained for the uncoated bubble. To investigate the mechanism of the enhanced nonlinearity, the bifurcation structure of the lipid coated MBs is studied for a wide range of MBs sizes and shell parameters. Consistent with the experimental results, we show that this unique oscillator can exhibit chaotic oscillations and higher order subharmonics at excitation amplitudes considerably below those predicted by the uncoated oscillator. Buckling or rupture of the shell and the dynamic variation of the shell elasticity causes the intensified non-linearity at low excitation pressure amplitudes. The simulated scattered pressure by single MBs are in good agreement with the experimental signals.
... This trial enrolled over 1,600 patients over 5 sites in the US and Canada, and included the very first patients in whom micro-US was used clinically in the world. The first outcome from this large trial was the development of a standardized reporting protocol termed PRI-MUS (prostate risk identification using micro-ultrasound) designed to help practitioners understand what csPCa looks like on real-time micro-US [13]. This 5-point grading system, much like PI-RADS for mpMRI, is not without its limitations, as the PRI-MUS score focuses exclusively on peripheral zone lesions; there is currently no well-established reference for anterior, transition zone, or central zone lesions. ...
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PurposeTo discuss the potential utility of newer imaging modalities including micro-ultrasound and PSMA-PET for the detection of clinically significant prostate cancer, technologies that may gain roles as adjuncts to multiparametric magnetic resonance imaging (mpMRI) in the active surveillance (AS) setting.Methods Narrative review of two new imaging modalities used for primary prostate cancer through April 2021. A targeted search was performed to identify current relevant literature on the role of new imaging modalities for primary prostate cancer using search terms “micro-ultrasound,” “molecular imaging,” “prostate cancer,” “active surveillance,” “multiparametric MRI,” “PI-RADS,” “PRI-MUS,” and “detection rate.” In addition, references of included articles were screened for further relevant publications.ResultsMicro-ultrasound (micro-US) and prostate-specific membrane antigen-positron emission tomography (PSMA-PET) are increasing in their use and applicability to prostate cancer imaging. Micro-US is used for cancer detection and may identify higher grade cancers more accurately than conventional ultrasound, despite technical hurdles in its initial launch. PSMA-PET is highly sensitive and specific for high-grade and metastatic prostate cancer, though costly and not easily available. Though data are sparse, it may have an emerging role in cancer diagnosis in select localized cases, and in some men considering (or currently on) AS who have indications of more aggressive disease.Conclusion There are very limited data on micro-US and PSMA-PET in AS patients. However, given the ability of these modalities to identify high-grade cancer, their judicious use in AS patients may be of utility in the future.
... This technology allows the operator to identify abnormal ductal anatomy and cell density, typically recognized as hypoechoic lesions using conventional ultrasound. Similar to PI-RADS, micro-ultrasound has a grading system known as prostate risk identification using micro-ultrasound (PRI-MUS) [77]. According to a meta-analysis by Zhang This systematic review and meta-analysis provides second level data describing the performance of MRI targeted biopsy compared to systematic biopsy in paired cohorts in which both biopsies were performed in the same patient, and finding no differences in prior biopsy status. ...
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Purpose of Review The goal of this study is to review recent findings and evaluate the utility of MRI transrectal ultrasound fusion biopsy (FBx) techniques and discuss future directions. Recent Findings FBx detects significantly higher rates of clinically significant prostate cancer (csPCa) than ultrasound-guided systematic prostate biopsy (SBx), particularly in repeat biopsy settings. FBx has also been shown to detect significantly lower rates of clinically insignificant prostate cancer. In addition, a dedicated prostate MRI can assist in more accurately predicting the Gleason score and provide further information regarding the index cancer location, prostate volume, and clinical stage. The ability to accurately evaluate specific lesions is vital to both focal therapy and active surveillance, for treatment selection, planning, and adequate follow-up. Summary FBx has been demonstrated in multiple high-quality studies to have improved performance in diagnosis of csPCa compared to SBx. The combination of FBx with novel technologies including radiomics, prostate-specific membrane antigen positron emission tomography (PSMA PET), and high-resolution micro-ultrasound may have the potential to further enhance this performance.
... Research has shown that each increase in PRI-MUS score is correlated with a 10.1% increase in the probability of csPCa presence. 99 The PRI-MUS scores obtained through mUS help guide risk stratification, biopsy technique, and the patient's course of treatment. Due to the recency of mUS integration as a novel technique for prostate imaging, the body of literature describing its effectiveness is limited. ...
Article
Transrectal ultrasound (TRUS) has been an invaluable tool in the assessment of prostate size, anatomy and aiding in prostate cancer (PCa) diagnosis for decades. Emerging techniques warrant an investigation into the efficacy of TRUS, how it compares to new techniques, and options to increase the accuracy of prostate cancer diagnosis. Currently, TRUS is used to guide both transrectal and transperineal biopsy approaches with similar cancer detection rates, but lower rates of infection have been reported with the transperineal approach, while lower rates of urinary retention are often reported with the transrectal approach. Multiparametric MRI has substantial benefits for prostate cancer diagnosis and triage such as lesion location, grading, and can be combined with TRUS to perform fusion biopsies targeting specific lesions. Micro-ultrasound generates higher resolution images that traditional ultrasound and has been shown effective at diagnosing PCa, giving it the potential to become a future standard of care. Finally, high-intensity focused ultrasound focal therapy administered via TRUS has been shown to offer safe and effective short-term oncological control for localized disease with low morbidity, and the precise nature makes it a viable option for salvage and repeat therapy.
... The new technique quickly caught the attention of researchers. As the first part of a recent multi-institutional randomized controlled trial of 1676 men with PCa suspicion (clinically qualified for biopsy), a standardized, upgraded protocol, based on the 29 MHz ExactVu™ system (Exact Imaging, Markham, Canada) -PRI-MUS (prostate risk identification using micro-ultrasound) protocol was established [47,48]. PRI-MUS, similarly to PI-RADS for mpMRI, consists of 5-point grading system, from 1 for very likely benign to 5 for very likely malignant ( Figure 2). ...
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The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) became recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure or exposure to the contrast agent. The novel ultrasound modalities such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS) or high frequency micro-ultra-sound (MicroUS) may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.
... This offers the opportunity for improved detection of high-grade cancers characterized by loss of normal acinar lumens and tighter cellular packing. As with PI-RADS for mpMRI, a prostate risk identification using mUS (PRI-MUS) protocol has been developed to standardize sonographic lesions [9]. In addition to superior resolution, this technology offers the convenience of conventional ultrasound such as real-time imaging and targeted biopsy during the same procedure, office-based set-up, relatively easy access compared with MRI, and considerably less expensive equipment. ...
Article
Objectives: To compare the performance of micro-ultrasound (mUS) with multi-parametric magnetic resonance imaging (mpMRI) in detecting clinically significant prostate cancer. Materials and Methods: Retrospective data from consecutive patients with any indication for prostate biopsy in 2 academic institutions were included. The operator, blinded to mpMRI, would first scan the prostate and annotate any mUS lesions. All mUS lesions were biopsied. Any mpMRI lesions that did not correspond to mUS lesion upon unblinding were additionally biopsied. Grade group (GG) ≥ 2 was considered clinically significant cancer. The Jeffreys interval method was used to compare performance of mUS with mpMRI with the non-inferiority limit set at −5%. Results: Imaging and biopsy were performed in 82 patients with 153 lesions. mUS had similar sensitivity to mpMRI (per-lesion analysis: 78.4% versus 72.5%), but lower specificity, positive predictive value, negative predictive value, and area under the curve. Micro-ultrasound found GG ≥ 2 in 13% of cases missed by mpMRI, while mpMRI found GG ≥ 2 in 11% of cases missed by mUS. The difference 0.020 (95% CI −0.070 to 0.110) was not statistically significant (P = 0.33). Conclusion: The sensitivity of mUS in detecting GG ≥ 2 disease was similar to that of mpMRI, but the specificity was lower. Further evaluation with a larger sample size and experienced operators is warranted.
... The new technique quickly caught the attention of researchers. As the first part of a recent multi-institutional randomized controlled trial of 1676 men with PCa suspicion (clinically qualified for biopsy), a standardized, upgraded protocol, based on the 29 MHz ExactVu™ system (Exact Imaging, Markham, ON, Canada)-PRI-MUS (prostate risk identification using micro-ultrasound) protocol was established [50,51]. PRI-MUS, similar to PI-RADS for mpMRI, consists of 5-point grading system, from 1 for very likely benign to 5 for very likely malignant ( Figure 2). ...
Article
Full-text available
The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) started to be recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure, or exposure to the contrast agent. The novel ultrasound modalities, such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS), or high frequency micro-ultrasound (Mi- croUS), may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.
... The recent development of high frequency "micro-ultrasound" technology allows for the visualization of tissue at higher resolution than conventional ultrasound. A qualitative scoring system based on visual analysis of micro-ultrasound images called the PRI-MUS (prostate risk identification using micro-ultrasound) protocol [6] has been proposed to estimate PCa likelihood. Several studies have shown that micro-ultrasound can detect PCa with sensitivity comparable to that of mp-MRI using this grading system [2,4]. ...
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MOTIVATION: Detection of prostate cancer during transrectal ultrasound-guided biopsy is challenging. The highly heterogeneous appearance of cancer, presence of ultrasound artefacts, and noise all contribute to these difficulties. Recent advancements in high-frequency ultrasound imaging - micro-ultrasound - have drastically increased the capability of tissue imaging at high resolution. Our aim is to investigate the development of a robust deep learning model specifically for micro-ultrasound-guided prostate cancer biopsy. For the model to be clinically adopted, a key challenge is to design a solution that can confidently identify the cancer, while learning from coarse histopathology measurements of biopsy samples that introduce weak labels. METHODS: We use a dataset of micro-ultrasound images acquired from 194 patients, who underwent prostate biopsy. We train a deep model using a co-teaching paradigm to handle noise in labels, together with an evidential deep learning method for uncertainty estimation. We evaluate the performance of our model using the clinically relevant metric of accuracy vs. confidence. RESULTS: Our model achieves a well-calibrated estimation of predictive uncertainty with area under the curve of 88$\%$. The use of co-teaching and evidential deep learning in combination yields significantly better uncertainty estimation than either alone. We also provide a detailed comparison against state-of-the-art in uncertainty estimation.
... Recently developed high frequency "micro-ultrasound" technology allows imaging the prostate at a much finer spatial resolution [20]. Clinical studies show that micro-ultrasound has a sensitivity comparable to mp-MRI using the qualitative ultrasound based "PRI-MUS" scoring system [21]- [23], and a recent meta-analysis of 13 published studies with 1125 participants concludes that micro-ultrasound guided biopsy has similar PCa detection rates as mp-MRI fusion biopsy [24]. However, analysis of RF data remain relatively unexplored for micro-ultrasound: these are limited to a single study using machine learning with QUS (Rohrbach et al. [25]) and two studies (Shao et al. [26], and Gilany et al. [27]) using deep learning. ...
Preprint
Deep learning-based analysis of high-frequency, high-resolution micro-ultrasound data shows great promise for prostate cancer detection. Previous approaches to analysis of ultrasound data largely follow a supervised learning paradigm. Ground truth labels for ultrasound images used for training deep networks often include coarse annotations generated from the histopathological analysis of tissue samples obtained via biopsy. This creates inherent limitations on the availability and quality of labeled data, posing major challenges to the success of supervised learning methods. On the other hand, unlabeled prostate ultrasound data are more abundant. In this work, we successfully apply self-supervised representation learning to micro-ultrasound data. Using ultrasound data from 1028 biopsy cores of 391 subjects obtained in two clinical centres, we demonstrate that feature representations learnt with this method can be used to classify cancer from non-cancer tissue, obtaining an AUROC score of 91% on an independent test set. To the best of our knowledge, this is the first successful end-to-end self-supervised learning approach for prostate cancer detection using ultrasound data. Our method outperforms baseline supervised learning approaches, generalizes well between different data centers, and scale well in performance as more unlabeled data are added, making it a promising approach for future research using large volumes of unlabeled data.
... The recent development of high frequency "micro-ultrasound" technology allows for the visualization of tissue at higher resolution than conventional ultrasound. A qualitative scoring system based on visual analysis of micro-ultrasound images called the PRI-MUS (prostate risk identification using micro-ultrasound) protocol [6] has been proposed to estimate PCa likelihood. Several studies have shown that micro-ultrasound can detect PCa with sensitivity comparable to that of mp-MRI using this grading system [2,4]. ...
Chapter
Full-text available
MOTIVATION: Detection of prostate cancer during transrectal ultrasound-guided biopsy is challenging. The highly heterogeneous appearance of cancer, presence of ultrasound artefacts, and noise all contribute to these difficulties. Recent advancements in high-frequency ultrasound imaging - micro-ultrasound - have drastically increased the capability of tissue imaging at high resolution. Our aim is to investigate the development of a robust deep learning model specifically for micro-ultrasound-guided prostate cancer biopsy. For the model to be clinically adopted, a key challenge is to design a solution that can confidently identify the cancer, while learning from coarse histopathology measurements of biopsy samples that introduce weak labels. METHODS: We use a dataset of micro-ultrasound images acquired from 194 patients, who underwent prostate biopsy. We train a deep model using a co-teaching paradigm to handle noise in labels, together with an evidential deep learning method for uncertainty estimation. We evaluate the performance of our model using the clinically relevant metric of accuracy vs. confidence. RESULTS: Our model achieves a well-calibrated estimation of predictive uncertainty with area under the curve of 88%. The use of co-teaching and evidential deep learning in combination yields significantly better uncertainty estimation than either alone. We also provide a detailed comparison against state-of-the-art in uncertainty estimation.
... These improvements enable improved visualization and targeting of suspicious regions as well as the systematic MicroUS guided prostate biopsy. 11 The second-generation system was released in 2017 with upgrades in electronics. Recently, there have been few publications investigating the ability of MicroUS in detecting csPCa, the majority of them using needle biopsy as pathologic proof. ...
Article
Objective : To determine the detection of clinically significant prostate cancer (csPCa) index lesion using high resolution transrectal micro-ultrasound (MicroUS) applying PRI-MUS (Prostate Risk Identification using Micro Ultrasound) score v1.0. Methods : Men who underwent radical prostatectomy following biopsy and MicroUS assessment were included. MicroUS dynamic cine loops of these patients were retrospectively reviewed by an experienced radiologist. The radiologist was aware that patients had undergone radical prostatectomy but was blinded to pathological data. Suspicious sites were assigned a PRI-MUS score. Radical prostatectomy specimens were examined with quarter mount technique. Detection rate of csPCa index lesion [Grade Group (GG) ≥2] by MicroUS was assessed at a patient level. Results : Twenty-five participants were included in the analysis. The median age was 65.5 years (range 56 - 74). Median PSA was 6.45 ng/dL (range 2 - 31.72). Two of 25 patients did not have csPCa (GG1 disease) on radical prostatectomy. MicroUS visualized 20/23 (87%) of the csPCa index lesions [median length 9 mm (range 1.5- 28.5)]. All identified lesions were categorized PRIMUS score 4 or 5. The 3 missed index lesions were in the transition zone [median length 10.5 mm (range 4.5-22.5)]. MicroUS missed 11 non index csPCa in 9 participants [median length 1.5 mm (range 1.5-10.5)]. Of these, 8 were GG2, two GG3 and one GG5. MicroUS identified the csPCa index lesion in all 9 of these men. Conclusion : MicroUS showed high sensitivity (87%) in detecting index lesions in the prostate gland and identified 100% of index lesions in the peripheral zone.
Article
Objective The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the diagnosis and management of prostate cancer (PC). Methods A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the diagnosis and therapeutic management of localised PC, while evaluating the references and their levels of evidence. Results The recommendations specify the genetics, epidemiology and means of diagnosing prostate cancer, as well as the notions of screening and early detection. MRI, the gold standard imaging examination for localised cancer, is recommended before prostate biopsies are performed. The transperineal approach reduces the risks of infection. The therapeutic methods are described and recommended according to the clinical context. Active surveillance is the gold standard of treatment for tumours with a low risk for progression. Early salvage radiotherapy is recommended in case of biochemical recurrence after radical prostatectomy. Imaging, particularly molecular imaging, helps to guide the decision-making in the event of biochemical recurrence after local treatment, but should not delay early salvage radiotherapy in the event of biological recurrence after radical prostatectomy. Conclusion This update of the French recommendations should help to improve the management of patients with PC.
Chapter
Prostate cancer (PC) was traditionally suspected on digital rectal examination (DRE) or increased prostatic specific antigen (PSA) and was diagnosed on transrectal biopsy. However, as stage migration in PC has evolved into earlier detection, an increasing number of newly diagnosed patients will have a normal DRE and even a low-level PSA. In this setting, imaging modalities have become a key component in assessing the patient with suspected PC. Conventional imaging strategies such as transrectal ultrasound, computed tomography (CT) of the abdomen and pelvis, and bone scan have traditionally been utilized to evaluate a patient with suspected PC. However, advances in imaging modalities and the emergence of newer technologies have expanded imaging studies to staging and assess disease progression in these patients. This chapter reviews the current role of conventional and newer imaging modalities when assessing patients with PC.
Chapter
Multispectral immunofluorescence (M-IF) analysis is used to investigate the cellular landscape of tissue sections and spatial interaction of cells. However, complex makeup of markers in the images hinders the accurate quantification of cell phenotypes. We developed DeepMIF, a new deep learning (DL) based tool with a graphical user interface (GUI) to detect and quantify cell phenotypes on M-IF images, and visualize whole slide image (WSI) and cell phenotypes. To identify cell phenotypes, we detected cells on the deconvoluted images followed by co-expression analysis to classify cells expressing single or multiple markers. We trained, tested and validated our model on \(>50k\) expert single-cell annotations from multiple immune panels on 15 samples of follicular lymphoma patients. Our algorithm obtained a cell classification accuracy and area under the curve (AUC) \(\ge 0.98\) on an independent validation panel. The cell phenotype identification took on average 27.5 min per WSI, and rendering of the WSI took on average 0.07 minutes. DeepMIF is optimized to run on local computers or high-performance clusters independent of the host platform. These suggest that the DeepMIF is an accurate and efficient tool for the analysis and visualization of M-IF images, leading to the identification of novel prognostic cell phenotypes in tumours.KeywordsDeep learningMultispectral immunofluorescenceCell detectionCell classificationImage viewer
Article
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Objectives To test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa). Materials and methods This is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone. Results The cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83. Conclusions T2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.
Article
Background The use of multiparametric magnetic resonance imaging (mpMRI) within active surveillance of prostate cancer programmes is identified by the UK National Institute for Health and Care Excellence (NICE guideline NG 131 2019) as having a role for monitoring disease. The widespread demands on mpMRI capacity may limit its use in surveillance. It is therefore timely to review the options that modern ultrasound imaging present to this cohort of patients in the monitoring of prostate cancer. Methods Between April and September 2020, 10 databases were searched to recruit studies for the review. Three reviewers evaluated the publications for inclusion. Characteristics including the inclusion criteria for the study cohort, how disease was determined, identification of disease progression, and the modality and mode of imaging used were reviewed. Given the paucity of full text articles, a meta-analysis was not possible. A narrative review was undertaken. Results In total, 12 studies, utilising the range of ultrasound parameters of B-mode, micro-ultrasound, colour Doppler, contrast ultrasound and elastography were included. The review demonstrated that micro-ultrasound offers promise as an imaging tool comparable with mpMRI. However, this is an emerging technology with limited availability. Analysis of the data further demonstrated that by combining the diagnostic features provided by multiple modes reviewed, ultrasound has a role in the diagnostic imaging of patients on active surveillance. Conclusion Providing a multiparametric approach is utilised, stable ultrasound findings may allow for increased intervals between biopsy for men on surveillance. The advent of micro-US offers promise as an imaging modality within an active surveillance pathway but requires further verification.
Chapter
Der konventionelle transrektale Ultraschall der Prostata ist trotz deutlicher Verbesserung der bildlichen Auflösung hinsichtlich der Sensitivität zur Visualisierung von suspekten Arealen eingeschränkt und dient vornehmlich zur ersten Begutachtung und Größenbestimmung der Prostata. Das Prostatakarzinom kann sich im Ultraschall durch ein vielfältiges Bild (z. B. hyper, oder hypoechogen) abzeichnen. Gute Ultraschallkenntnisse, Zeit und natürlich ein Ultraschallgerät mit exzellentem B-Bild sind Voraussetzung, um überhaupt Aussagen hinsichtlich der Früherkennung eines Prostatakarzinoms treffen zu können. Gerade die Schwierigkeit der Beurteilung solcher auffälligen Areale, auch mangels einer Standardisierung bei der Durchführung und Bewertung der Ultraschallbilder, bedarf Innovationen, um diese urologische Untersuchung zu vereinfachen und die Genauigkeit zu verbessern.
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Der Ultraschall fand zunächst in den technischen Disziplinen Anwendung, bevor er zu medizinischen Zwecken genutzt wurde. Er diente bereits zu Beginn des 20. Jahrhunderts zur Echolotung in der Schifffahrt und findet bis in die Gegenwart z. B. in der Materialprüfung Anwendung. Grundlage dafür war die Entdeckung des piezoelektrischen Effektes durch die Brüder Curie und der damit verbundenen Möglichkeit, durch Umwandlung elektrischer in mechanische Energie Ultraschallwellen zu erzeugen. Seit Anfang der 1940er Jahre, ausgehend von den Gebrüdern Dussik (1942), fanden Ultraschallverfahren schnell Anwendung in der Medizin und haben sich seitdem in eindrucksvoller Weise als bildgebendes Verfahren in Ergänzung der bekannten herkömmlichen Techniken der Röntgendiagnostik etabliert. Die Sonographie entwickelte sich in nahezu allen klinischen Fachdisziplinen zur Methode der ersten Wahl und stellt inzwischen das am häufigsten eingesetzten Verfahren der Bildgebung dar. Zu diagnostischen Ultraschalluntersuchungen des Urogenitaltraktes erfolgten bereits in den 60’er Jahren des vorigen Jahrhunderts erste Anwendungen (Holmes 1966 und Goldberg et al. 1968), die maßgebend für die „Uro-Sonographie“ in ihrer weiteren Entwicklung waren. Nahezu sensationell war die Einführung der transrektalen Sonographie zur Beurteilung der Prostata (Watanabe et al. 1973) als endosonographische Untersuchungsmethode ebenso wie die Nutzung der Duplex-Sonographie in Zusammenhang mit der Farbgebung (FKDS: farbcodierte Duplexsonographie), die über die Wiedergabe der morphologischen Strukturen der Bildgebung hinaus auch die Beurteilung der Durchblutung im Bereich der „region of interest“ ermöglicht. Damit ist die Uro-Sonographie zu einem integralen unersetzbaren Bestandteil im Spektrum der sonographischen Möglichkeiten in der Humanmedizin geworden.
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The recommendations on carrying out a multiparametric magnetic resonance imaging (mpMRI) for the primary diagnostics and during active surveillance of prostate cancer, include as a consequence an image-guided sampling from conspicuous areas. In doing so, the information on the localization provided by mpMRI is used for a targeted biopsy of the area suspected of being a tumor. The targeted sampling is mainly performed under sonographic control and after fusion of MRI and ultrasound but can also be (mostly in special cases) carried out directly in the MRI scanner. In an ultrasound-guided biopsy, it is vital to coregister the MR images with the ultrasound images (segmentation of the contour of the prostate and registration of suspect findings). This coregistration can either be carried out cognitively (transfer by the person performing the biopsy alone) or software based. Each method shows specific advantages and disadvantages in the prioritization between diagnostic accuracy and resource expenditure.
Article
Introduction: Magnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population. Material and methods: We retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve. Results: Overall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 - 0.843). Conclusion: In our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results.
Article
Introduction and objective: ExactVuTM is a real-time micro-ultrasound system which provides, according to the Prostate Risk Identification Using Micro-Ultrasound protocol (PRI-MUS), a 300% higher resolution compared to conventional transrectal ultrasound. To evaluate the performance of ExactVuTM in the detection of Clinically significant Prostate Cancer (CsPCa). Materials and methods: Patients with Prostate Cancer diagnosed at fusion biopsy were imaged with ExactVuTM. CsPCa was defined as any Gleason Score ≥ 3+4. ExactVuTM examination was considered as positive when PRI-MUS score was ≥ 3. PRI-MUS scoring system was considered as correct when the fusion biopsy was positive for CsPCa. A transrectal fusion biopsy- proven CsPCa was considered as a gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operator characteristic (ROC) curve (AUC) were calculated. Results: 57 patients out of 68 (84%) had a csPCa. PRI-MUS score was correctly assessed in 68% of cases. Regarding the detection of CsPCa, ExactVuTM 's sensitivity, specificity, PPV, and NPV was 68%, 73%, 93%, and 31%, respectively and the AUC was 0.7 (95% CI 0.5-0-8). For detecting CsPCa in the transition/ anterior zone the sensitivity, specificity, PPV, and NPV was 45%, 66%, 83% and 25% respectively ant the AUC was 0.5 (95% CI 0.2-0.9). Accounting only the CsPCa located in the peripheral zone, sensitivity, specificity, PPV, and NPV raised up to 74%, 75%, 94%, 33%, respectively with AUC 0.75 (95% CI 0.5-0-9). Conclusions: ExactVuTM provides high resolution of the prostatic peripheral zone and could represent a step forward in the detection of CsPCa as a triage tool. Further studies are needed to confirm these promising results.
Article
Background Multiparametric MRI has led to increased detection of clinically significant prostate cancer (csPCa). Micro-US is being investigated for csPCa detection. Purpose To compare multiparametric MRI and micro-US in detecting csPCa (grade group ≥2) and to determine the proportion of MRI nodules visible at micro-US for real-time targeted biopsy. Materials and methods This prospective, single-center trial enrolled biopsy-naive men with suspected prostate cancer (PCa) between May 2019 and September 2020. All patients underwent multiparametric MRI followed by micro-US; findings at both were interpreted in a blinded fashion, followed by targeted biopsy and nontargeted systematic biopsy using micro-US. Proportions were compared using the exact McNemar test. The differences in proportions were calculated. Results Ninety-four men (median age, 61 years; IQR, 57-68 years) were included. MRI- and micro-US-targeted biopsy depicted csPCa in 37 (39%) and 33 (35%) of the 94 men, respectively (P = .22); clinically insignificant PCa in 14 (15%) and 15 (16%) (P > .99); and cribriform and/or intraductal PCa in 14 (15%) and 13 (14%) (P > .99). The MRI- plus micro-US-targeted biopsy pathway depicted csPCa in 38 of the 94 (40%) men. The addition of nontargeted systematic biopsy to MRI- plus micro-US-targeted biopsy did not enable identification of any additional men with csPCa but did help identify nine additional men with clinically insignificant PCa (P = .04). Biopsy was avoided in 32 of the 94 men (34%) with MRI and nine of the 94 men (10%) with micro-US (P < .001). Among 93 MRI targets, 62 (67%) were prospectively visible at micro-US. Conclusion MRI and micro-US showed similar rates of prostate cancer detection, but more biopsies were avoided with the MRI pathway than with micro-US, with no benefit of adding nontargeted systematic biopsy to the MRI- plus micro-US-targeted biopsy pathway. Most MRI lesions were prospectively visible at micro-US, allowing real-time targeted biopsy. ClinicalTrials.gov registration no.: NCT03938376 © RSNA, 2022 Online supplemental material is available for this article.
Article
Objective: To prospectively determine the value of post-MRI micro-ultrasonography (microUS) in the diagnosis of transition zone (TZ) significant prostate cancer (sPCa). Patients and methods: Eighty-four consecutive men (66 ± 6.3 years) with a mean PSA level of 10.2 ± 7.4 ng/mL and at least one TZ-PI-RADS > 2 lesion were included. All patients had MRI-directed microUS and biopsy. Sensitivity and specificity of post-MRI microUS to visualize PI-RADS > 2 TZ lesions, the cancer detection rate of TZ-sPCa, and tumor characteristics according to their visibility on microUS were evaluated. Interreader agreement for detecting microUS+ lesions was evaluated using Cohen's kappa test. Results: Of the 92 PI-RADS > 2 lesions, 71 (71/92; 77%) were visible on microUS and biopsy was performed without image fusion, which was required for the 21 invisible lesions (21/92; 22.8%). TZ-sPCa detection rate was 51.1% (47/92). Sensitivity and specificity of MRI-directed microUS were 83% (39/47; 95% CI: 69.2-92.4%) and 28.9% (13/45; 95% CI: 16.4-44.3%), on a per-lesion basis and 86.4% (38/45; 95% CI: 72.6-94.8%) and 27.5% (11/40; 95% CI: 14.6-43.9%) on a per-patient basis. Visible tumors on microUS exhibited a larger volume and a lower mean ADC value than non-visible tumors (15.8 ± 5.1 vs. 12.5 ± 3.6 mm and 0.82 ± 1.1 × 103 vs. 0.9 ± 1.4 × 10-3 mm2/s) (p = 0.02). Non-visible tumors showed a heterogeneous non-specific echotexture or were masked by the shadowing caused by corpora amylacea. Interreader agreement was almost perfect (kappa = 0.88; 95% CI: 0.79-0.95). The main limitation is the single-center feature of the study. Conclusion: MRI-targeted transrectal microUS is effective to detect TZ-sPCa. TRUS-MRI image fusion helps overcome limitations due to TZ tissue heterogeneity. Key points: microUS can visualize the majority of MRI-detected PI-RADS > 2 TZ lesions (sensitivity = 83%). Interreader agreement of MRI-directed microUS in the detection of TZ lesions appears excellent (kappa = 0.88). In 77% of PI-RADS > 2 TZ lesions, biopsy was performed under microUS visual control. MRI fusion system was only used to overcome limitations due to tissue heterogeneity of benign prostatic hyperplasia.
Article
Background The PRIMUS (prostate risk identification using micro-ultrasound) classification was developed in 2016 to assess suspicious zones in the peripheral zone of the prostate using micro-ultrasound. The prostate is roughly divided into a peripheral zone and a transitional zone, to which large portions of the anterior prostate belong. The question now is whether it can also be used for the whole prostate to detect clinically significant prostate tumors.MethodsA total of 399 prostate biopsies were performed on 372 patients using the ExactVu™ micro-ultrasound system (Exact Imaging, Markham, Canada) between January 2018 and May 2019 at the Ordens Hospital in Linz, Austria. Median prostate-specific antigen (PSA) was 6.7 ng/ml (interquartile range [IQR] 4.5–11.2 ng/ml), and 30% had positive palpation of the prostate. Suspicious zones were classified in real time according to PRIMUS, and a transrectal ultrasound-guided (TRUS) biopsy was performed in the same session using micro-ultrasound. Histologic findings were compared with micro-ultrasound findings.ResultsBiopsy yielded cancer diagnoses in 60% of patients, whereby Gleason grade group (GG) > 1 tumors were found in 42% of patients. PRIMUS classification had an area under the curve (AUC) of 0.76 for the prediction of a GG > 1 tumor in the peripheral zone. Accuracy was 0.68–0.83, depending on the prostate region, with the highest accuracy found in the apex and the lowest accuracy in the base of the prostate. Targets in the anterior prostate were biopsied, but generally not classified according to PRIMUS since the classification is currently validated only for the peripheral zone. However, PRIMUS classification was performed in 33 of the 737 specimens from the anterior prostate, for which accuracy was seen with an AUC of 0.8.Conclusion Micro-ultrasound and PRIMUS classification are useful tools for the detection of prostate cancer and show good diagnostic accuracy throughout the prostate. This makes it possible to reduce the high rate of false-negatives for prostate biopsies, while avoiding the need for examiner-intensive multimodal investigations, such as prostate magnetic resonance imaging.
Article
Background: To compare the detection rate of micro-ultrasound with multiparametric magnetic resonance imaging targeted biopsy (mpMRI-TB) for prostate cancer diagnosis. Methods: The studies on micro-ultrasound prostate biopsy for prostate cancer diagnosis were searched in PubMed, Cochrane library and EMBASE databases from inception to April.2021. we performed a systematic review and cumulative meta-analysis based on search results using Software Rev-Man 5.3. Results: A total of 11 studies involving 1081 patients were included. The Meta-analysis showed that no significant difference was found between micro-ultrasound and mpMRI-TB in the total detection of prostate cancer(OR:1.01, 95%CI:0.85~1.21, p=0.89), of Grading Groups(GG)=1(OR: 0.92, 95%CI:0.68~1.25, p=0.59),of GG≥2(OR:1.01, 95%CI:0.83~1.22, p=0.92), and of GG≥3(OR: 1.31, 95%CI:0.95~1.81, p=0.10). Conclusions: Micro-ultrasound guided prostate biopsy provides comparable detection rates for prostate cancer diagnosis with the mpMRI-TB, which is expected to challenge mpMRI-TB in the diagnosis of prostate cancer.
Article
Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in males. Traditional tools for screening and diagnosis, such as prostate-specific antigen, digital rectal examination and conventional transrectal ultrasound (TRUS), present low accuracy for PCa detection. Multiparametric MRI has become a game changer in the PCa diagnosis pathway and MRI-targeted biopsies are currently recommended for males at risk of clinically significant PCa, even in biopsy-naïve patients. Recent advances in ultrasound have also emerged with the goal to provide a readily accessible and cost-effective tool for detection of PCa. These newer techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach, multiparametric ultrasound. High frequency Micro-ultrasound has emerged as a promising imaging technology for PCa diagnosis. Initial results have shown high sensitivity of Micro-ultrasound in detecting PCa in addition to its potential in improving the accuracy of targeted biopsies, based on targeting under real-time visualization, rather than relying on cognitive/fusion software MRI-transrectal ultrasound-guided biopsy.
Article
Objective: To compare the efficacy of multiparametric magnetic resonance imaging (mpMRI)-directed and micro-ultrasonography (micro-US)-directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa). Materials and methods: A total of 203 patients were prospectively enrolled at three institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after the micro-US targets had been assessed. After unblinding, targets were then sampled using software-assisted fusion, followed by systematic samples. The primary outcome measure was non-inferiority of micro-US to detect csPCa, with a detection ratio of at least 80% that of mpMRI. Results: A total of 79 csPCa cases were detected overall (39%). Micro-US-targeted biopsy detected 58/79 cases (73%), while mpMRI-targeted biopsy detected 60/79 (76%) and non-targeted (completion sampling) samples detected 45/79 cases (57%). mpMRI-targeted samples alone detected 7/79 (9%) csPCa cases which were missed by micro-US-targeted and non-targeted samples. Three of these seven were anterior lesions with 2/7 in the transition zone. Micro-US-targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 cases (5%). Micro-US was non-inferior to mpMRI and detected 97% of the csPCa cases detected by mpMRI-targeted biopsy (95% CI 80-116%; P = 0.023). Conclusions: This is the first multicentre prospective study comparing micro-US-targeted biopsy with mpMRI-targeted biopsy. The study provides further evidence that micro-US can reliably detect cancer lesions and suggests that micro-US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis.
Conference Paper
In order to evaluate the diagnostic accuracy of high-resolution ultrasound (HRUS) for detection of prostate cancer, it must be validated against whole-mount pathology. An ex-vivo HRUS scanning system was developed and tested in phantom and human tissue experiments to allow for in-plane computational co-registration of HRUS with magnetic resonance imaging (MRI) and whole-mount pathology. The system allowed for co-registration with an error of 1.9mm±1.4mm, while also demonstrating an ability to allow for lesion identification.Clinical Relevance- Using this system, a workflow can be established to co-register HRUS with MRI and pathology to allow for the diagnostic accuracy of HRUS to be determined with direct comparison to MRI.
Article
Introduction. — Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. Methods. — Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS ≥ 3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician’s discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern ≥ 4 at histology. Results. — In all, 148 patients with a median age of 69 years (IQR 63—74) and median PSA density of 0.16 ng/ml/cc (0.10—0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). Conclusion. — Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy. © 2022 Elsevier Masson SAS. All rights reserved.
Article
Despite the continuous technical progress regarding the transrectal ultrasonography of the prostate (TRUS) and its successful use in combination with magnetic resonance imaging (MRI) in MRI-targeted biopsy, there is no radiologic modality being able to rule out clinically significant prostate cancer without the need of systematic biopsy. In the past few years, TRUS regained more attention due to the development of high frequency ultrasound as well as the combination of different ultrasonic modalities like shear wave elastography and contrast-enhanced sonography (CEUS). Currently, multiparametric MRI (mpMRI)-targeted biopsy shows the best results concerning detection rates, sensitivity and specificity of clinically significant prostate cancer compared to systematic biopsy. In the future, transperineal biopsy is probably going to increasingly replace the transrectal biopsy approach. For both approaches, transrectal ultrasonography is necessary to display the prostate and to detect suspicious lesions. Therefore future improvements in transrectal ultrasonography can be expected.
Article
BACKGROUND: MRI has been proposed as a new staging tool for bladder cancer (BC), but use is limited by its high costs and low availability. 29-MHz high-resolution micro-ultrasound (mUS) technology has been suggested as an alternative to detect BC and distinguish between muscle-invasive and non-muscle invasive BC. OBJECTIVE: The aim was to compare the diagnostic accuracy of mUS vs. magnetic resonance imaging (MRI) in differentiating NMIBC and MIBC at definitive pathological examination. METHODS: This is a prospective study of patients with a primary diagnosis of BC with either positive urine cytology (UC) or negative UC and a tumor size > 25 mm from a tertiary care high volume center. mUS, with the ExactVu system with an EV29L 29 MHz side-fire transducer, and a 3-Tesla MRI were performed before transurethral resection of bladder tumor (TURBT) in every patient before undergoing TURBT. We compared the imaging results with pathological reports. RESULTS: The analyzed population consisted of 58 individuals. The reported mUS and MRI sensitivity, specificity, positive, and negative predictive values were 85.0%, 76.3%, 65.4%, and 90.6%, versus 85.0%, 50.0%, 47.2%, and 86.4%, respectively. In accuracy analysis, the AUC for mUS and MRI were respectively 0.807 and 0.675. CONCLUSIONS: In our population mUS seems to have a better performance in distinguishing NMIBC from MIBC. The main limitation of mUS is the probe shape that makes its use problematic in cases with a large prostate and inadequate rectal preparation. Further studies with a larger population are ongoing to compare and validate these techniques in this setting.
Article
Introduction Multiparametric MRI (mpMRI) has become the standard imaging technique for the diagnosis of prostate cancer. However, mpMRI pathways are depending on experience, expertise, and information transfer from radiology to urology. Micro-ultrasound (Micro-US) is a new system, using high frequency (up to 29 MHz) and high resolution (down to 75 µm) ultrasound images. We evaluated the diagnostic performance of Micro-US in the detection of the prostate cancer index lesion and compared its performance to mpMRI using pathological whole mount sections as the reference. Materials and Methods We retrospectively reviewed the data of 32 patients with diagnosis of prostate cancer and scheduled for radical prostatectomy and who underwent Micro-US before surgery. Still images and cineloops of Micro-US were recorded. Sixteen patients had also mpMRI images with acceptable quality and complete sequences available. For validation purposes each prostate was partitioned into 12 sectors for a total of 192 sectors evaluated. Micro-US and mpMRI images were both scored according to a validated system (PRI-MUS and Pi-RADS) where a score ≥3 was suspicious for both scores. Preoperative and postoperative results regarding the identification of the index lesion, the biggest lesion visible, were then compared and sensitivity, specificity, negative and positive predictive values, and accuracy were calculated. Results Median age was 67 years, median PSA was 6.2ng/ml, and median cancer volume of the index lesion was 3.1cc. The sensitivity of Micro-US in the index lesion detection was 76.5%, specificity 76.6%, negative predictive value 85.6%, positive predictive value 64.1% and 76.6% of accuracy. The sensitivity of mpMRI was 65.1%, specificity 93.4%, negative predictive value 83.2%, positive predictive value 84.3%, and 81.8% of accuracy (all p> .05). Conclusion Micro-US showed good reliability in identifying prostate cancer index lesions. Its performance is comparable to that of mpMRI.
Article
Despite the continuous technical progress regarding the transrectal ultrasonography of the prostate (TRUS) and its successful use in combination with magnetic resonance imaging (MRI) in MRI-targeted biopsy, there is no radiologic modality being able to rule out clinically significant prostate cancer without the need of systematic biopsy. In the past few years, TRUS regained more attention due to the development of high frequency ultrasound as well as the combination of different ultrasonic modalities like shear wave elastography and contrast-enhanced sonography (CEUS). Currently, multiparametric MRI (mpMRI)-targeted biopsy shows the best results concerning detection rates, sensitivity and specificity of clinically significant prostate cancer compared to systematic biopsy. In the future, transperineal biopsy is probably going to increasingly replace the transrectal biopsy approach. For both approaches, transrectal ultrasonography is necessary to display the prostate and to detect suspicious lesions. Therefore future improvements in transrectal ultrasonography can be expected.
Article
Purpose of review: Multiparametric magnetic resonance imaging (mpMRI) has fundamentally changed how intraprostatic lesions are visualized, serving as a highly sensitive means for detecting clinically significant prostate cancer (csPCa) via image-targeted biopsy. However, limitations associated with mpMRI have led to the development of new imaging technologies with the goal of better characterizing intraprostatic disease burden to more accurately guide treatment planning and surveillance for prostate cancer focal therapy. Herein, we review several novel imaging modalities with an emphasis on clinical data reported within the past two years. Recent findings: 7T MRI, artificial intelligence applied to mpMRI, positron emission tomography combined with either computerized tomography or MRI, contrast-enhanced ultrasound, and micro-ultrasound are novel imaging modalities with the potential to further improve intraprostatic lesion localization for applications in focal therapy for prostate cancer. Many of these technologies have demonstrated equivalent or favorable diagnostic accuracy compared to contemporary mpMRI for identifying csPCa and some have even shown improved capabilities to define lesion borders, to provide volumetric estimates of lesions, and to assess the adequacy of focal ablation of planned treatment zones. Summary: Novel imaging modalities with capabilities to better characterize intraprostatic lesions have the potential to improve accuracy in treatment planning, real-time assessment of the ablation zone, and posttreatment surveillance; however, many of these technologies require further validation to determine their clinical utility.
Article
Introduction Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. Methods Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS ≥ 3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern ≥ 4 at histology. Results In all, 148 patients with a median age of 69 years (IQR 63–74) and median PSA density of 0.16 ng/ml/cc (0.10–0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). Conclusion Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy.
Article
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Background The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. Methods 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. Results Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). Conclusions TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.
Article
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Prostate cancer is the most prevalent form of cancer in western men. An accurate early localization of prostate cancer, permitting efficient use of modern focal therapies, is currently hampered by a lack of imaging methods. Several methods have aimed at detecting microvascular changes associated with prostate cancer with limited success by quantitative imaging of blood perfusion. Differently, we propose contrast-ultrasound diffusion imaging, based on the hypothesis that the complexity of microvascular changes is better reflected by diffusion than by perfusion characteristics. Quantification of local, intravascular diffusion is performed after transrectal ultrasound imaging of an intravenously injected ultrasound contrast agent bolus. Indicator dilution curves are measured with the ultrasound scanner resolution and fitted by a modified local density random walk model, which, being a solution of the convective diffusion equation, enables the estimation of a local, diffusion-related parameter. Diffusion parametric images obtained from five datasets of four patients were compared with histology data on a pixel basis. The resulting receiver operating characteristic (curve area = 0.91) was superior to that of any perfusion-related parameter proposed in the literature. Contrast-ultrasound diffusion imaging seems therefore to be a promising method for prostate cancer localization, encouraging further research to assess the clinical reliability.
Article
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Transrectal ultrasound-guided systemic biopsy is the recommended method in most cases with suspicion of prostate cancer. Transrectal periprostatic injection with a local anesthetic may be offered as effective analgesia; periprostatic nerve block with 1% or 2% lidocaine is the recommended form of pain control. On initial biopsy, a minimum of 10 systemic, laterally directed cores is recommended, with more cores in larger glands. Extended prostate biopsy schemes, which require cores weighted more laterally at the base (lateral horn) and medially to the apex, show better cancer detection rates without increasing adverse events. Transition zone biopsies are not recommended in the first set of biopsies, owing to low detection rates. One set of repeat biopsies is warranted in cases with persistent indication. Saturation biopsy (>/=20 cores) should be reserved for repeat biopsy in patients who have negative results on initial biopsy but who are still strongly suspected to have prostate cancer.
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The purpose of this study was to assess the role of color Doppler ultrasonography and power Doppler ultrasonography in the identification of diffuse prostatic lesions. Forty male patients underwent gray scale transrectal ultrasonography, color and power Doppler sonography, and transrectal ultrasonographically guided biopsy. Transrectal ultrasonographically guided biopsy revealed cancer in 23 patients and benign lesions in 17 patients. Among the prostatic cancers 82.6% (19 of 23) showed increased flow signals, whereas 23.5% (four of 17) of benign lesions showed increased flow signals on color or power Doppler ultrasonography. If we consider increased flow signal on color or power Doppler sonography as a sign of a prostate cancer in diffuse prostatic lesions, these modalities have a sensitivity of 82.6%, specificity of 76.5%, and positive predictive value of 82.6%. On the basis of our study, we may conclude that color and power Doppler ultrasonography are useful in the identification of diffuse prostatic lesions.
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While systematic 12-core (S12C) biopsy detects more cancers than sextant biopsy, to our knowledge the clinical significance of these additionally detected tumors has not been established. We studied pathological parameters of prostatectomy specimens from patients undergoing radical prostatectomy for prostate cancer detected with a S12C biopsy to determine the clinical significance of these cancers in comparison with sextant detected cancers. A total of 179 consecutive patients undergoing radical prostatectomy for clinically localized prostate cancer detected by S12C biopsy were studied. The groups compared consisted of the sextant core subset of the S12C and the entire S12C set. Total tumor volume, Gleason score, organ confined status, surgical margin status, seminal vesicle invasion, lymph node involvement, and clinical significance of tumors detected by sextant and by S12C templates were compared. S12C biopsy detected a greater number of cancers scored as moderate (Gleason score 2 to 6) or high (Gleason score 7 or greater) grade, and cancers of all sizes regardless of organ confined status than the sextant cores alone (all p <0.05). S12C biopsy identified a greater number of biologically significant and insignificant tumors regardless of how they were defined. Compared with the sextant set S12C biopsy detects a significantly greater number of surgically curable, biologically significant tumors as well as those that might be considered clinically insignificant.
Article
Objectives: To determine how high-resolution transrectal ultrasound (HiTRUS) compares with conventional TRUS (LoTRUS) for the visualization of prostate cancer. Methods and materials: Twenty-five men with known prostate cancer scheduled for radical prostatectomy were preoperatively imaged with both LoTRUS (5MHz) and HiTRUS (21MHz). Dynamic cine loops and still images for each modality were saved and subjected to blinded review by a radiologist looking for hypoechoic foci ≥ 5 mm in each sextant of the prostate. Following prostatectomy, areas of prostate cancer ≥ 5 mm on pathologic review were anatomically correlated to LoTRUS and HiTRUS findings. The accuracy of LoTRUS and HiTRUS to visualize prostate cancer in each sextant of the prostate and to identify high-grade and locally advanced disease was assessed. The McNemar test was used to compare sensitivity and specificity and paired dichotomous outcomes between imaging modalities. Results: Among 69 sextants with pathologically identified cancerous foci at radical prostatecomy, HiTRUS visualized 45 and missed 24, whereas LoTRUS visualized 26 and missed 43. Compared with LoTRUS, HiTRUS demonstrated improved sensitivity (65.2% vs. 37.7%) and specificity (71.6% vs. 65.4%). HiTRUS's agreement with pathologic findings was twice as high as LoTRUS (P = 0.006). HiTRUS provided a nonsignificant increase in visualization of high-grade lesions (84% vs. 60%, P = 0.11). Conclusions: HiTRUS appears promising for prostate cancer imaging. Our initial experience suggests superiority to LoTRUS for the visualization of cancerous foci, and supports proceeding with a clinical trial in the biopsy setting.
Article
We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance. A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy. Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p>0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p=0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively. Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.
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The use of confidence intervals has become standard in the presentation of statistical results in medical journals. Calculation of confidence limits can be straightforward using the normal approximation with an estimate of the standard error, and in particular cases exact solutions can be obtained from published tables. However, for a number of commonly used measures in epidemiology and clinical research, formulae either are not available or are so complex that calculation is tedious. The author describes how an approach to confidence interval estimation which has been used in certain specific instances can be generalized to obtain a simple and easily understood method that has wide applicability. The technique is applicable as long as the measure for which a confidence interval is required can be expressed as a monotonic function of a single parameter for which the confidence limits are available. These known confidence limits are substituted into the expression for the measure--giving the required interval. This approach makes fewer distributional assumptions than the use of the normal approximation and can be more accurate. The author illustrates his technique by calculating confidence intervals for Levin's attributable risk, some measures in population genetics, and the "number needed to be treated" in a clinical trial. Hitherto the calculation of confidence intervals for these measures was quite problematic. The substitution method can provide a practical alternative to the use of complex formulae when performing interval estimation, and even in simpler situations it has major advantages.
Article
To test the hypothesis that men with prostate cancer (PCA) and preoperative disease features considered favorable for focal treatment would be accurately characterized with transrectal biopsy and prostate magnetic resonance imaging (MRI) by performing a retrospective analysis of a selected cohort of such patients treated with radical prostatectomy (RP). A total of 202 patients with PCA who had preoperative MRI and low-risk biopsy criteria (no Gleason grade 4/5, 1 involved core, < 2 mm, PSA density < or = 0.10, clinical stage < or = T2a) were included in the study. Indolent RP pathology was defined as no Gleason 4/5, organ confined, tumor volume < 0.5 mL, and negative surgical margins. MRI ability to locate and determine the tumor extent was assessed. After RP, 101 men (50%) had nonindolent cancer. Multifocal and bilateral tumors were present in 81% and 68% of patients, respectively. MRI indicated extensive disease in 16 (8%). MRI sensitivity to locate PCA ranged from 2% to 20%, and specificity from 91% to 95%. On univariate analysis, MRI evidence of extracapsular extension (P = .027) and extensive disease (P = .001) were associated with nonindolent cancer. On multivariate analysis, only the latter remained as significant predictor (P = .0018). Transrectal biopsy identified men with indolent tumors favorable for focal treatment in 50% of cases. MRI findings of extracapsular extension and extensive tumor involving more than half of the gland are associated with unfavorable features, and may be useful in excluding patients from focal treatment. According to these data, endorectal MRI is not sufficient to localize small tumors for focal treatment.
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To determine the ability of transrectal ultrasound to detect early localized prostate cancer, unsuspected (nonpalpable) cancer in the contralateral lobe of patients undergoing radical prostatectomy for clinically localized disease was evaluated. A total of 59 patients with palpable prostate cancer clinically confined to 1 lobe underwent transrectal ultrasound before radical prostatectomy and step-sectioning of the radical prostatectomy specimen. Transrectal ultrasound was performed with 5 or 7 MHz. real-time transrectal units. Pathological findings in these 59 cases revealed no tumor in the contralateral lobe in 34 (58%) and the presence of unsuspected tumor in 25 (42%). Transrectal ultrasound detected 13 of 25 unsuspected cancers for a sensitivity of 52%. Of 34 patients with no contralateral lobe lesion transrectal ultrasound was correct in 23 for a specificity of 68%. The positive and negative predictive values for transrectal ultrasound in this study group were 54 and 66%, respectively. There was no significant difference in the pathological size of the clinically suspected and clinically unsuspected cancers as measured by average largest dimension, and transrectal ultrasound sensitivity did not correlate with the size of the cancer. Based on careful sonopathological analysis, transrectal ultrasound may not be a good method to detect clinically unsuspected prostate cancer and the false positive rate would appear to be high.
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A new reproducibility index is developed and studied. This index is the correlation between the two readings that fall on the 45 degree line through the origin. It is simple to use and possesses desirable properties. The statistical properties of this estimate can be satisfactorily evaluated using an inverse hyperbolic tangent transformation. A Monte Carlo experiment with 5,000 runs was performed to confirm the estimate's validity. An application using actual data is given.
Article
Fifty-two patients with clinical stage A and B carcinomas of the prostate were imaged by ultrasound (US) transrectally with a 5-MHz linear array transducer and transabdominally with a 3-MHz sector scanner prior to radical prostatectomy. The fresh specimens of 44 prostate glands were scanned in a water bath with a 5-MHz linear array transducer in multiple planes. In all cases, histopathologic correlation was obtained. Prostatic carcinoma presented as an echopenic lesion in 54% of the specimens, as a slightly hypoechoic area in 22%, and could not be identified in 24% because of its isoechoic characteristics. In contrast to many previous reports, no instance of echogenic cancer was observed.
Article
Not all prostate cancers are sonographically hypoechoic or palpable on digital rectal examination, and suspicious areas on transrectal prostatic ultrasonography or digital rectal examination often are not cancer. We present quadrant biopsy results from a multicenter prostate cancer screening study in which men were evaluated with prostate specific antigen (PSA) and digital rectal examination. If the PSA level was elevated (greater than 4.0 ng./ml., Hybritech Tandem assay) or digital rectal examination was suspicious quadrant biopsies were performed. Biopsy specimens were labeled separately, and histological findings were correlated by quadrant with the findings on ultrasonography and digital rectal examination. Of the 6,630 subjects enrolled into the study 16% were biopsied. Of 1,002 quadrants that were suspicious on digital rectal examination 110 (11%) had cancer, while 308 of 418 quadrants containing cancer (74%) were not suspicious on digital rectal examination. Of 855 quadrants that were sonographically suspicious 153 (18%) had cancer, while 282 of 435 quadrants containing cancer (65%) were not sonographically suspicious. Of 225 patients with cancer 137 (61%) would have been missed if only the exact site of the palpable induration had been biopsied. Of 251 patients with cancer 131 (52%) would have been missed if only the exact site of the hypoechoic lesion had been biopsied. We conclude that digital rectal examination and transrectal ultrasonography have limited accuracy in identifying and localizing prostate cancer. Our study emphasizes the importance of obtaining systematic biopsies if the PSA level is elevated, even in the absence of digital rectal examination or ultrasound anomalies.
Article
The aim of this prospective study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy. A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound (TRUS) and underwent TRUS-guided core biopsy. All patients had 8 or 10 standardized biopsy samples taken, with the number depending on the size of the gland. Additional biopsy samples were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the standardized biopsies (ie, target biopsies). The sensitivity of the detection of cancer for different combinations of biopsy samples was analyzed and compared with that of our model with 8 to 10 biopsies. In all, 276 cancers were detected, of which 88 (32%) had an isoechoic appearance. Sensitivity was 59% for focal lesions detected by TRUS, 85% to 97% for different combinations of systematic biopsy samples, and 93% to 98% for a combination of systematic and target biopsy samples. The sensitivity for the standard sextant protocol was 85%. By adding target biopsies, the sensitivity increased to 93%. The standard sextant protocol leaves 15% of cancers undetected compared with results obtained from a more extensive biopsy procedure. By combining systematic and target sampling, the sensitivity increases; however, a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated.
Article
We performed a prospective study to assess gray-scale and color and power Doppler sonography for the detection of prostatic cancer and to determine the impact of operator experience. Four radiologists with prior experience using gray-scale and Doppler imaging and four urologists with prior experience limited to gray-scale imaging performed sextant biopsies on 251 patients. Each biopsy site was prospectively scored for gray-scale and Doppler abnormality. Cancer was detected in 211 biopsy sites from 85 patients. Overall agreement between sonographic findings and biopsy results as measured with the kappa statistic was minimally superior to chance (kappa = 0.12 for gray-scale, kappa = 0.11 for color Doppler, kappa < or =0.09 for power Doppler). With respect to gray-scale diagnosis of cancer, the performance of radiologists (kappa = 0.12) and urologists (kappa = 0.13) was similar. With respect to power Doppler, the performance of radiologists (kappa = 0.09) was superior to that of urologists (kappa = -0.03, p<0.002). Among patients with at least one positive biopsy for cancer, foci of increased power Doppler flow detected by a radiologist were 4.7 times more likely to contain cancer than adjacent tissues without flow. Gray-scale and Doppler imaging did not reveal prostatic cancer with sufficient accuracy to avoid sextant biopsy. Power Doppler may be useful for targeted biopsies when the number of biopsy passes must be limited. There is benefit from increased operator experience with Doppler imaging, but there is no demonstrable benefit of power Doppler over conventional color Doppler sonography.
Article
To assess the detection of prostate cancer with contrast material-enhanced transrectal sonography. Sixty subjects were examined with conventional gray-scale, harmonic gray-scale, and power Doppler sonography. Evaluation was repeated during intravenous infusion of contrast agent. Gray-scale imaging was performed in continuous mode and with intermittent imaging by using interscan delay times of 0.5, 1.0, 2.0, and 5.0 seconds. Sextant biopsy sites were scored prospectively as benign or malignant at baseline imaging and again during enhanced transrectal sonography. Prostate cancer was present in 37 biopsy sites from 20 subjects. Baseline imaging demonstrated prostate cancer in 14 sites in 11 subjects. Enhanced transrectal sonography depicted prostate cancer in 24 sites in 15 subjects. Each of the five subjects in whom prostate cancer was missed had only a single biopsy core with positive findings (Gleason score < or = 6). In three of these five subjects, prostate cancer made up less than 10% of the core. The improvement in sensitivity from 38% (14 of 37 malignant foci) at baseline to 65% (24 of 37 malignant foci) with contrast enhancement was significant (P<.004, McNemar chi(2) test). Specificity was similar at baseline (267 [83%] of 323 malignant foci) and during enhanced transrectal sonography (257 [80%] of 323 malignant foci). Clustered receiver operating characteristic analysis demonstrated significant improvement in diagnostic accuracy during enhanced transrectal sonography (P =.027). Enhanced transrectal sonography improves sensitivity for the detection of malignant foci within the prostate without substantial loss of specificity. Low-volume tumors with a Gleason score of 6 or less may not be detected with enhanced transrectal sonography.
Article
The diagnosis of prostate cancer is currently limited by the low sensitivity and specificity of systematic conventional grey-scale ultrasonography. We assessed contrast-enhanced colour Doppler ultrasonography by means of a microbubble ultrasound contrast agent to detect tumour vascularity and improve the diagnosis of prostate cancer. The use of a microbubble ultrasound contrast agent for transrectal colour Doppler targeted biopsy significantly improved the detection of prostate cancer compared with systematic biopsy following conventional grey-scale ultrasonography (p<0.001). Contrast-agent enhanced colour Doppler imaging may allow for limited targeted biopsies (five or less), which reduces costs and morbidity.
Article
To determine the utility of Power Doppler enhanced transrectal ultrasound (PD-TRUS) and its guided prostate biopsies in men with prostate specific antigen (PSA) levels between 2.5 and 10 ng/ml and to evaluate its impact on prostate cancer (PCa) detection in men undergoing first and repeat biopsies. A total of 136 consecutive referred men with serum total PSA (Abbott Laboratories, Abbott Park, IL, USA) levels between 2.5 and 10 ng/ml (mean age 64 +/- 9 years, range 45-82) and a normal digital rectal examination were included. 101 underwent a first biopsy whereas 35 had repeat biopsy. Gray-scale transrectal ultrasound (TRUS), and PD-TRUS (B&K Medical, Denmark) were performed in lithotomy position before and during the biopsy procedure. Vascularity accumulation and perfusion characteristics were recorded and graded as normal or abnormal in the peripheral zone of the prostate. A Vienna-nomogram based biopsy regime was performed in all patients on first biopsy and a special biopsy regime on repeat biopsy plus additional biopsies from abnormal sites on PD-TRUS. Overall PCa detection rate was 34.7% and 25.7% and abnormal accumulation on PD-TRUS was identified in 42.3% and 48.6% on first and repeat biopsy, respectively. The PCa detection rate, on first and repeat biopsy in patients with and without PD-TRUS accumulation were 67.4% versus 10.3% (p < 0.001) and 47.05% versus 5.6% (p = 0.0049), respectively. PD-TRUS directed biopsies were positive in 5.7% and 11.1% on first and repeat biopsy whereas PCa detection using the routine prostate biopsy regime was 94.3% and 88.9% on first and repeat biopsy. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PD-TRUS signal alone for PCa detection on first biopsy was 82.8%, 78.8%, 87.9% and 89.7%, respectively, and 88.8%, 68.0%, 47.0% and 94.4% on repeat biopsy, respectively. In comparison, the results PD-TRUS guided biopsies were 53.8%, 59.1%, 16.7%, and 89.5%, on first biopsy, respectively, and 20.0%, 13.3%, 23.5%, 11.1% on repeat biopsy, respectively. Negative PD-TRUS signal is able to exclude most of the patients without PCa in the PSA range of 2.5-10 ng/ml. As an additional tool at TRUS biopsy PD-TRUS has a high negative predictive value and may help to reduce the number of unnecessary biopsies.
Article
Transrectal ultrasound (TRUS) guided multiple systematic random biopsies are presently the method of choice for determining the presence or absence of prostate cancer. TRUS image information is only used to guide the biopsy needle into the prostate, but not to localize and target cancerous lesions. Our aim in this study was to evaluated the possible predictive value of tumor suspicious endosonographic lesions of the prostate for prostate biopsies. We prospectively compared six systematic biopsies with lesion guided biopsies in a consecutive series of 217 patients. All patients had a prostate specific antigen (PSA) level of >4 ng/ml without a history of prostate disease. In a subgroup of 145 men with sonomorphologic lesions suggestive for prostate cancer (hypoechoic areas or asymmetries predominantly in the peripheral zone), lesion-guided biopsies were taken in addition to the systematic biopsies. We evaluated the number of tumors which were diagnosed or missed by both of the biopsy strategies. Of the 217 evaluated patients, 64 (29%) had histology confirmed cancer. Four patients with negative sextant biopsies had a positive TRUS guided biopsy. Out of 145 patients with a normal TRUS, three were cancer positive by sextant biopsy. A total of 1,387 individual biopsy cores were evaluated. Of the 1,304 systematic biopsy cores, 182 (14%) were positive and 1,122 (86%) negative. Of the 329 TRUS lesion guided biopsy cores 139 (42%) were positive and 190 (58%) negative. Patients with tumor suggestive TRUS lesions have a considerably higher risk of being diagnosed with prostate cancer compared to patients without such lesions. Both systematic sextant and TRUS lesion guided biopsies missed detectable prostate cancer in a minority of patients. Taking the endosonographic morphology of the prostate gland into consideration for biopsy strategies may improve the quality of the biopsy and avoid unnecessary invasive procedures in selected cases.
Article
The aim of this study was to reproduce prostate cancer (PCA) localization by MRI based on prostatic sextants (right and left base, middle, and apex) with minimal systematic error. Combined endorectal/body-phased-array-coil MRI of the prostate at 1.5 T was retrospectively evaluated twice, with an interval of more than 1 month, by each of two independent radiologists (R1 readings R11 and R12, and R2 readings R21 and R22) in 23 patients (age 51-75 years) who had radical prostatectomy within 1 month of MRI. PCA stage was pT2 in 14 patients, and pT3 in nine. Median Gleason score was 7 (range 5-9). Histopathology showed 83 sextants with PCA and 55 without. Reproducibility of sextant positions was within one MRI slice (3 mm) in over 80% of cases. For PCA localization, ROC analysis (AUC=0.584+/-0.048-0.724+/-0.043) yielded no significant intra-reader differences. R11 and R21 differed slightly (P=0.035). Intra-observer agreement (kappa=0.52-0.58) exceeded inter-observer agreement (kappa=0.35-0.45). Intra-observer Spearman correlation (r=0.72-0.74) exceeded inter-observer correlation (r=0.43-0.51) for sextants with PCA, but not for sextants without (r=0.69-0.74). Per-sextant localization and reporting provides a highly reliable framework in MRI of the prostate. MRI of the prostate should be followed up by the same radiologists to minimize systematic error of interpretation.
Article
An extended prostate biopsy schema has been advocated at initial prostate biopsy to decrease the rate of false-negative cancer cases. However, critics have raised concerns that this may lead to the greater detection of clinically insignificant cancers. We examined the impact of using an extended pattern schema on cancer detection and also on the finding of smaller and clinically insignificant cancer. Clinical data, including patient age, race, prebiopsy prostate specific antigen (PSA), digital rectal examination, prostate volume, number of needle cores and biopsy findings were abstracted from the medical records of all patients who underwent prostate biopsy in a 5-year period. Extended pattern prostate biopsy was defined as more than 10 cores. Clinically insignificant cancer was defined as a maximal tumor dimension of 1.0 cm or less, Gleason sum 6 or less and organ confined disease at radical prostatectomy. Adjusted regression models were developed to assess the independent effects of using an extended biopsy pattern on the detection of cancer overall and on the detection of clinically insignificant cancer. A total of 740 men with a mean age of 62.6 years were referred for prostate biopsy. Median PSA was 5.7 ng/ml and prostate volume was 39.7 cc. The OR for detecting prostate cancer was 1.55 (95% CI 1.09 to 2.19) for the extended pattern compared with standard biopsy. Of the subset of 136 patients who underwent radical prostatectomy 12.6% had clinically insignificant cancer. However, in contrast to overall cancer detection, extended pattern prostate biopsy was not found to be associated with an increased risk of detecting smaller or clinically insignificant cancer. PSA density was the single parameter found to be independently associated with the detection of clinically insignificant cancer (95% CI 0.20 to 0.98). Using an extended prostate biopsy pattern involving more than 10 cores increases the likelihood of detecting prostate cancer. A significant association between more needle cores at initial prostate biopsy and finding smaller and clinically insignificant cancer was not apparent.
Article
Transrectal ultrasound (TRUS) is an important tool for urologists and radiologists in the detection of prostate cancer. Various TRUS-guided biopsy techniques are applied in clinical practice. Frequently, only the detection rates achieved with these methods are compared. Other diagnostic performance parameters, particularly the specificity and negative predictive value, are seldom compared. After extensive assessment of the available literature, this review describes the methods of TRUS-guided biopsy for prostate cancer detection. A distinction was made between systematic biopsies and biopsies that target a perceived (hypoechoic or Doppler-enhancing) lesion on imaging. Subsequently, the diagnostic performance (sensitivity, specificity, positive and negative predictive values, accuracies) was compared between these techniques. Imaging-guided biopsy showed better diagnostic performance than systematic biopsy with higher sensitivity. The combinations of sensitivity and specificity were highest for colour Doppler and contrast-enhanced targeted biopsy. Studies targeting hypoechoic lesions had relatively high sensitivity, but specificity was low. Presently however, with widespread prostate-specific antigen screening, fewer prostate cancers are hypoechoic, and the value of targeting hypoechoic lesions has diminished. Performing colour or contrast-enhanced Doppler biopsy or adding these techniques to systematic biopsies improves diagnostic performance, particularly by increasing sensitivity.
Article
We reported on the results of a sequential cohort study comparing office based saturation prostate biopsy to traditional 10-core sampling as an initial biopsy. Based on improved cancer detection of office based saturation prostate biopsy repeat biopsy, we adopted the technique as an initial biopsy strategy to improve cancer detection. Two surgeons performed 24-core saturation prostate biopsies in 139 patients undergoing initial biopsy under periprostatic local anesthesia. Indication for biopsy was an increased PSA of 2.5 ng/dl or greater in all patients. Results were compared to those of 87 patients who had previously undergone 10-core initial biopsies. Cancer was detected in 62 of 139 patients (44.6%) who underwent saturation biopsy and in 45 of 87 patients (51.7%) who underwent 10-core biopsy (p >0.9). Breakdown by PSA level failed to show benefit to the saturation technique for any degree PSA increase. Men with PSA 2.5 to 9.9 ng/dl were found to have cancer in 53 of 122 (43.4%) saturation biopsies and 26 of 58 (44.8%) 10-core biopsies. Complications included 3 cases of prostatitis in each group. Rectal bleeding was troublesome enough to require evaluation only in 3 men in the saturation group and 1 in the 10-core group. Although saturation prostate biopsy improves cancer detection in men with suspicion of cancer following a negative biopsy, it does not appear to offer benefit as an initial biopsy technique. These findings suggest that further efforts at extended biopsy strategies beyond 10 to 12 cores are not appropriate as an initial biopsy strategy.
Article
In contemporary practice, most prostate cancers are either invisible on ultrasound or indistinguishable from concurrent benign prostatic hyperplasia. Diagnosis therefore rests on prostate biopsy. Biopsies are not simply directed at ultrasonically visible lesions, as these would miss many cancers; rather the whole gland is sampled. The sampling itself is systematic, using patterns based on prostate zonal anatomy and the geographical distribution and frequency of cancer. This review explains the evolution of the prostate biopsy technique, from the classical sextant biopsy method to the more recent extended biopsy protocols (8, 10, 12, >12 and saturation biopsy protocols). Extended protocols are increasingly being used to improve diagnostic accuracy, especially in those patients who require repeat biopsy. This trend has been facilitated by the ongoing improvement in safety and acceptability of the procedure, particularly with the use of antibiotic prophylaxis and local anaesthesia. The technical details of these extended protocols are discussed, as are the current data regarding procedure-related morbidity and how this may be minimized.
Article
Ultrasound imaging of the prostate is commonly used to assess the size of the gland and for needle placement during systematic biopsy. Ultrasound evaluation of prostate cancer is limited by difficulty in distinguishing benign from malignant tissue. Although Doppler techniques may provide some improvement in the detection of prostate cancer, targeted biopsy based on conventional ultrasound with Doppler is not sufficient to replace systematic biopsy. Contrast-enhanced ultrasound imaging techniques that employ microbubble contrast agents represent an innovative approach to imaging of the neovascularity associated with prostate cancer. This review describes the application of contrast-enhanced ultrasound to improve detection and assessment of prostate cancer.
Article
To identify the clinical characteristics of anterior prostate cancers (APCs) and to compare these with posterior prostate cancers (PPCs). We reviewed 1290 consecutive open and laparoscopic radical prostatectomies (RPs) at the authors' institution from January 2000 to March 2004. Prostates were processed using a whole-mount technique. Each surgical specimen was reviewed by one pathologist, and tumour areas were marked, measured and mapped. Positive surgical margins (PSMs) were defined as the presence of cancer cells at the inked surface of the specimen. Specimens were then categorized by the location of their dominant tumour, i.e. pure anterior, anterior > posterior, posterior > anterior, or pure posterior. We compared the clinical and pathological characteristics of 259 patients in the pure-anterior group with the 594 in the pure-posterior group. Before RP, APCs had a significantly lower biopsy Gleason score (78% vs 68% with Gleason 4-6), fewer mean biopsy cores positive (2.0 vs 2.6), a smaller median percentage of positive cores (17% vs 26%), lower clinical stage (T1 in 79% vs 62%), and higher progression-free probability estimated by preoperative nomogram (86% vs 84%) than PPCs. Patients with APCs also had more previous negative biopsy sessions. The pathological analysis of RP specimens showed that those with APCs had higher tumour volume (1.6 vs 0.83 mL) and had a higher PSM rate (12% vs 7%) than those with PPCs, despite specimens with PPCs having higher rates of extraprostatic extension (10% vs 19%). APCs have lower Gleason grade and lower rates of extraprostatic extension, yet patients with anterior tumours have higher overall tumour volumes and higher PSM rates. Because current tools for detecting and staging prostate cancer can underestimate the extent of anterior prostate disease, improved methods are needed for localizing and characterizing anterior cancers.
Article
Prostate cancer is the most commonly diagnosed malignancy in men. Gray-scale ultrasound-guided systematic biopsy is the standard of care for prostate cancer detection in men with an elevated prostate-specific antigen or an abnormal digital rectal examination. Systematic biopsy may miss up to 35% of clinically relevant cancers. Color and power Doppler ultrasound, ultrasound contrast agents, and elastography have and will dramatically change the role of ultrasound in prostate cancer diagnosis. Several reports have demonstrated that contrast-enhanced ultrasound investigations of the blood flow of the prostate allow for prostate cancer visualization and therefore, for targeted biopsies. Comparisons between systematic and contrast-enhanced ultrasound-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores. Furthermore, contrast-enhanced ultrasound has been shown to detect cancers with higher Gleason scores compared with the systematic approach, which seems to improve prostate cancer grading. In addition, elastography is a new ultrasound technique that allows for the assessment of tissue elasticity. Contrast-enhanced ultrasound and elastography improve prostate cancer detection and may be useful for prostate cancer grading and staging. Future clinical trials will be needed to determine the promise of these new advances for ultrasound of the prostate evolving into clinical applications.
Article
To assess the use of real-time elastography (RTE) for detecting prostate cancer in patients scheduled for radical prostatectomy (RP), as most solid tumours differ in their consistency from the deriving tissue, and RTE might offer a new tool for cancer detection. We examined 15 patients (mean age 56 years, sd 6.2, range 46-71) with RTE, using an ultrasonography (US) system with a 7.5-MHz transrectal probe as a transducer. RTE is capable of visualizing displacements between pairs of US images of tissues when placed under axial compression. The stiffness of the lesion was displayed from blue (soft) to black (hard). Hard lesions with a diameter of > or = 5 mm were considered as malignant. All patients had the diagnosis of prostate cancer confirmed by biopsy and had a mean (range) prostate specific antigen (PSA) level of 4.6 (1.4-16.1) ng/mL; all were scheduled for RP. US was performed by two investigators and interpreted by consensus. Cancer location and size was determined in the RTE mode only. One pathologist classified tumour location, grade and stage. The RTE findings were compared with the pathological findings. There were no major complications during RP in any patient; all had a pT2 tumour on histopathological examination, the Gleason score was 5-9 and the mean (range) tumour size 1.1 (0.6-2.5) cm. Thirty-five foci of prostate cancer were present at the pathological evaluation; multiple foci were found in 11 of the 15 glands. RTE detected 28 of 35 cancer foci (sensitivity 80%). The per-patient analysis showed that RTE detected at least one cancer area in each of the 15 patients. Only four sites with false-positive findings on RTE and no histopathological correlation were detected; these findings were obtained in the first five patients (period of learning). RTE can be used to visualize differences in tissue elasticity. Our results show that RTE allows the detection of prostate cancer and estimation of tumour location and size. RTE of the prostate is a new imaging method with great potential for detecting prostate cancer.
Article
To compare detection of prostate cancer and distribution of Gleason scores with gray-scale, color Doppler, and elastographic imaging. Prostate biopsy patients were evaluated with gray-scale, color Doppler, and elastographic imaging. Targeted biopsy cores were obtained along with six laterally directed systematic sextant cores. Pathologic results were correlated with imaging findings. Prostate cancer was detected in 60 of 137 patients (43.8%). Cancer was detected in 241 (14%) of 1703 biopsy cores, including 90 (20%) of 448 targeted cores, 106 (13%) of 818 sextant cores, and 45 (10%) of 437 transition zone cores. Sonographic abnormality was associated with cancer: gray-scale odds ratio (OR) = 3.19, P = 0.011; color Doppler OR = 1.86, P = 0.041; elastography OR = 2.53; P = 0.007. Although targeted cores were more likely than sextant cores to detect cancer (OR = 1.82, P = 0.004), no sonographic abnormality was found in 57 (53.8%) of 106 of positive sextant sites. A linear trend for increasing Gleason score was present with gray-scale (P <0.001) imaging, color Doppler imaging (P <0.005), and elastography (P <0.001). Abnormal color flow was strongly associated with Gleason score 8 to 10 lesions but not with lower-grade lesions. Elastography demonstrated a positive association with Gleason scores of 5 to 10. Targeted cores based on gray-scale, color Doppler, and elastographic imaging are more likely to return positive biopsy results as compared with systematic biopsy cores. Although color Doppler imaging and elastography are encouraging adjuncts to improve cancer detection, targeted biopsy alone is not sufficient to replace the traditional sextant biopsy technique.