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Prostate evaluation for clinically important disease: Sampling using image-guidance or not? (The PRECISION study, NCT02380027)

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... However, multiparametric (mp) MRI-TRUS fusion guided biopsy strategies have given urologists a targeted approach that enables prioritized sampling to areas suspicious for harboring cancer. 3,4 Using this approach, the addition of two biopsy cores to lesions visible with MRI resulted in 30% higher rate of detection of high-risk and 17% less detection of low-risk tumors. 5 Despite these promising results, there is evidence in the literature that the addition of two targeted cores may still not be optimal, and may leave the index lesion undersampled. ...
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Objectives The objective of this study was to determine if spatial distribution of multiparametric magnetic resonance imaging–transrectal ultrasound (mpMRI-TRUS) fusion biopsy cores to the index lesion reveals trends in the detection of intra-lesion Gleason heterogeneity and a more optimal prostate biopsy strategy. Methods Index lesion was the lesion with longest diameter on T2-weighted (T2W)-MRI. In cohort 1, fusion biopsy cores biopsies were taken in areas in the center of the target as well as 1 cm laterally on each side. For cohort 2, targeted biopsies were taken from the center of the lesion only. Heterogeneity was defined as difference in maximum Gleason score obtained from fusion cores in the center of the index lesion versus cores obtained from the periphery (cohort 1), or any difference in maximum Gleason score obtained from fusion cores targeted to the index lesion (cohort 2) compared with systematic 12 cores TRUS biopsy. Results Ninety-nine consecutive patients (35 and 64 in cohorts 1 and 2, respectively) with median age (SD) and prostate-specific antigen (PSA) of 66.9 (±5.9) and 9.7 (±8.2) respectively, were included. Age, PSA, Prostate Imaging Reporting and Data System (PI-RADS) score, and preoperative MRI lesion size were not significantly different between cohorts. Gleason heterogeneity was observed at a significantly higher rate in cohort 1 versus cohort 2 (58% versus 24%; p = 0.041). In cohort 1, cores obtained from the center of the lesion had higher Gleason score than cores obtained from the periphery of the targeted lesion in 57% of cases. Conclusions We demonstrate that there is observable tumor heterogeneity in biopsy specimens, and that increased number of cores, as well as cores focused on the center and periphery of the largest lesion in the prostate, provide more comprehensive diagnostic information about the patient’s clinical risk category than taking nonspecific cores targeted within the tumor.
... Computer-aided diagnosis models for detection of prostate cancer and guidance of biopsy involve both ultrasound (US)-and mp-MRI-based tissue characterization. mp-MRI has high sensitivity in detection of prostate lesions but low specificity [1,10], hence, limiting its utility in detecting disease progression over time [15]. US-based tissue characterization methods focus on the analysis of texture [11] and spectral features [7] within a single ultrasound frame, Doppler imaging and elastography [13]. ...
Conference Paper
The ubiquity of noise is an important issue for building computer-aided diagnosis models for prostate cancer biopsy guidance where the histopathology data is sparse and not finely annotated. We propose a solution to alleviate this challenge as a part of Temporal Enhanced Ultrasound (TeUS)-based prostate cancer biopsy guidance method. Specifically, we embed the prior knowledge from the histopathology as the soft labels in a two-stage model, to leverage the problem of diverse label noise in the ground-truth. We then use this information to accurately detect the grade of cancer and also to estimate the length of cancer in the target. Additionally, we create a Bayesian probabilistic version of our network, which allows evaluation of model uncertainty that can lead to any possible misguidance during the biopsy procedure. In an in vivo study with 155 patients, we analyze data from 250 suspicious cancer foci obtained during fusion biopsy. We achieve the average area under the curve of 0.84 for cancer grading and mean squared error of 0.12 in the estimation of tumor in biopsy core length.
... where ⨀ is an element-wise multiplication and c t is calculated as: c t = φ(W ci x t + W cℎ ℎ t − 1 + b c ), (7) In this equation, the W term represents weight matrices; e.g., W ci is the input-memory weight matrix. Input gate i, and forget gate f determine the degree that new information is to be added and current information is to be removed, respectively, as follows: ...
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Temporal Enhanced Ultrasound (TeUS), comprising the analysis of variations in backscattered signals from a tissue over a sequence of ultrasound frames, has been previously proposed as a new paradigm for tissue characterization. In this manuscript, we propose to use deep Recurrent Neural Networks (RNN) to explicitly model the temporal information in TeUS. By investigating several RNN models, we demonstrate that Long Short-Term Memory (LSTM) networks achieve the highest accuracy in separating cancer from benign tissue in the prostate. We also present algorithms for in-depth analysis of LSTM networks. Our in vivo study includes data from 255 prostate biopsy cores of 157 patients. We achieve area under the curve, sensitivity, specificity, and accuracy of 0.96, 0.76, 0.98 and 0.93, respectively. Our result suggests that temporal modeling of TeUS using RNN can significantly improve cancer detection accuracy over previously presented works.
Conference Paper
Prostate cancer is the most common cancer and second most common cause of cancer death in men in the UK. However, the patient risk from the cancer can vary considerably, and the widespread use of prostate-specific antigen (PSA) screening has led to over-diagnosis and over-treatment of low-grade tumours. It is therefore important to be able to differentiate high-grade prostate cancer from the slowly- growing, low-grade cancer. Many of these men with low-grade cancer are placed on active surveillance (AS), which involves constant monitoring and intervention for risk reclassification, relying increasingly on magnetic resonance imaging (MRI) to detect disease progression, in addition to TRUS-guided biopsies which are the routine clinical standard method to use. This results in a need for new tools to process these images. For this purpose, it is important to have a good TRUS-MR registration so corresponding anatomy can be located accurately between the two. Automatic segmentation of the prostate gland on both modalities reduces some of the challenges of the registration, such as patient motion, tissue deformation, and the time of the procedure. This thesis focuses on the use of deep learning methods, specifically convolutional neural networks (CNNs), for prostate cancer management. Chapters 4 and 5 investigated the use of CNNs for both TRUS and MRI prostate gland segmentation, and reported high segmentation accuracies for both, Dice Score Coefficients (DSC) of 0.89 for TRUS segmentations and DSCs between 0.84-0.89 for MRI prostate gland segmentation using a range of networks. Chapter 5 also investigated the impact of these segmentation scores on more clinically relevant measures, such as MRI-TRUS registration errors and volume measures, showing that a statistically significant difference in DSCs did not lead to a statistically significant difference in the clinical measures using these segmentations. The potential of these algorithms in commercial and clinical systems are summarised and the use of the MRI prostate gland segmentation in the application of radiological prostate cancer progression prediction for AS patients are investigated and discussed in Chapter 8, which shows statistically significant improvements in accuracy when using spatial priors in the form of prostate segmentations (0.63 ± 0.16 vs. 0.82 ± 0.18 when comparing whole prostate MRI vs. only prostate gland region, respectively).
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Convolutional neural networks (CNNs) have recently led to significant advances in automatic segmentations of anatomical structures in medical images, and a wide variety of network architectures are now available to the research community. For applications such as segmentation of the prostate in magnetic resonance images (MRI), the results of the PROMISE12 online algorithm evaluation platform have demonstrated differences between the best-performing segmentation algorithms in terms of numerical accuracy using standard metrics such as the Dice score and boundary distance. These small differences in the segmented regions/boundaries outputted by different algorithms may potentially have an unsubstantial impact on the results of downstream image analysis tasks, such as estimating organ volume and multimodal image registration, which inform clinical decisions. This impact has not been previously investigated. In this work, we quantified the accuracy of six different CNNs in segmenting the prostate in 3D patient T2-weighted MRI scans and compared the accuracy of organ volume estimation and MRI-ultrasound (US) registration errors using the prostate segmentations produced by different networks. Networks were trained and tested using a set of 232 patient MRIs with labels provided by experienced clinicians. A statistically significant difference was found among the Dice scores and boundary distances produced by these networks in a non-parametric analysis of variance (p < 0.001 and p < 0.001, respectively), where the following multiple comparison tests revealed that the statistically significant difference in segmentation errors were caused by at least one tested network. Gland volume errors (GVEs) and target registration errors (TREs) were then estimated using the CNN-generated segmentations. Interestingly, there was no statistical difference found in either GVEs or TREs among different networks, (p = 0.34 and p = 0.26, respectively). This result provides a real-world example that these networks with different segmentation performances may potentially provide indistinguishably adequate registration accuracies to assist prostate cancer imaging applications. We conclude by recommending that the differences in the accuracy of downstream image analysis tasks that make use of data output by automatic segmentation methods, such as CNNs, within a clinical pipeline should be taken into account when selecting between different network architectures, in addition to reporting the segmentation accuracy.
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Introduction The classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores. Methods This is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer. Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10–12-core TRUS biopsy. The main inclusion criteria are a serum PSA ≤20 ng/mL, a digital rectal examination finding of T2 or less and no prior prostate biopsy. The primary outcome is the proportion of men with clinically significant cancer detected. A sample size of at least 470 patients is required. Key secondary outcomes include the proportion of clinically insignificant cancer detected. Ethics and dissemination Ethical approval was obtained from the National Research Ethics Committee East Midlands, Leicester (15/EM/0188). Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. Registration details NCT02380027; Pre-results
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Background: The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI). Objective: To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer. Design, setting, and participants: Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS). Intervention: Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer. Outcome measurements and statistical analysis: Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs. Results and limitations: The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92-0.98] vs 0.91 [95% CI 0.86-0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer. Conclusions: An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines. Patient summary: We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money.
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Importance Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy, and brachytherapy vs active surveillance. Design, Setting, and Participants Population-based prospective cohort of 1141 men (57% participation among eligible men) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposures Treatment with radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main Outcomes and Measures Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pretreatment) and 3, 12, and 24 months after treatment. The instrument contains 4 domains—sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems—each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point. Results Of 1141 enrolled men, 314 pursued active surveillance (27.5%), 469 radical prostatectomy (41.1%), 249 external beam radiotherapy (21.8%), and 109 brachytherapy (9.6%). After propensity weighting, median age was 66 to 67 years across groups, and 77% to 80% of participants were white. Across groups, propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction, 20.8 to 22.8 for urinary obstruction and irritation, 9.7 to 10.5 for urinary incontinence, and 5.7 to 6.1 for bowel problems. Compared with active surveillance, mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy (36.2 [95% CI, 30.4-42.0]), external beam radiotherapy (13.9 [95% CI, 6.7-21.2]), and brachytherapy (17.1 [95% CI, 7.8-26.6]). Compared with active surveillance at 3 months, worsened urinary incontinence was associated with radical prostatectomy (33.6 [95% CI, 27.8-39.2]); acute worsening of urinary obstruction and irritation with external beam radiotherapy (11.7 [95% CI, 8.7-14.8]) and brachytherapy (20.5 [95% CI, 15.1-25.9]); and worsened bowel symptoms with external beam radiotherapy (4.9 [95% CI, 2.4-7.4]). By 24 months, mean scores between treatment groups vs active surveillance were not significantly different in most domains. Conclusions and Relevance In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings can be used to promote treatment decisions that incorporate individual preferences.
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The EQ-5D is a widely used questionnaire that describes and values health related quality of life. Recently, a five level version was developed. Updated methods to estimate values for all health states are required. Data: 996 respondents representative of the English general population completed Time Trade-Off (TTO) and Discrete Choice Experiment (DCE) tasks. Methods: We estimate models, with and without interactions, using DCE data only; TTO data only; and TTO/DCE data combined. TTO data are interpreted as both left and right censored. Heteroskedasticity and preference heterogeneity between individuals is accounted for. We use maximum likelihood estimation in combination with Bayesian methods. The final model is chosen using the deviance information criterion (DIC). Results: Censoring and taking account of heteroskedasticity has important effects on parameter estimation. Regarding DCE, models with different dimension parameters and similar level parameters are best. Considering models for both TTO and DCE/TTO combined, models with parameters for all dimensions and levels perform best, as judged by the DIC. Taking account of heterogeneity improves fit, and a three latent group multinomial model has the lowest DIC. Conclusion: Studies to elicit values for the EQ-5D-5L need new approaches to estimate the underlying value function. This paper presents approaches which suit the characteristics of these data and recognise preference heterogeneity.
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Purpose To determine the interobserver reproducibility of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon. Materials and Methods This retrospective HIPAA-compliant study was institutional review board-approved. Six radiologists from six separate institutions, all experienced in prostate magnetic resonance (MR) imaging, assessed prostate MR imaging examinations performed at a single center by using the PI-RADS lexicon. Readers were provided screen captures that denoted the location of one specific lesion per case. Analysis entailed two sessions (40 and 80 examinations per session) and an intersession training period for individualized feedback and group discussion. Percent agreement (fraction of pairwise reader combinations with concordant readings) was compared between sessions. κ coefficients were computed. Results No substantial difference in interobserver agreement was observed between sessions, and the sessions were subsequently pooled. Agreement for PI-RADS score of 4 or greater was 0.593 in peripheral zone (PZ) and 0.509 in transition zone (TZ). In PZ, reproducibility was moderate to substantial for features related to diffusion-weighted imaging (κ = 0.535-0.619); fair to moderate for features related to dynamic contrast material-enhanced (DCE) imaging (κ = 0.266-0.439); and fair for definite extraprostatic extension on T2-weighted images (κ = 0.289). In TZ, reproducibility for features related to lesion texture and margins on T2-weighted images ranged from 0.136 (moderately hypointense) to 0.529 (encapsulation). Among 63 lesions that underwent targeted biopsy, classification as PI-RADS score of 4 or greater by a majority of readers yielded tumor with a Gleason score of 3+4 or greater in 45.9% (17 of 37), without missing any tumor with a Gleason score of 3+4 or greater. Conclusion Experienced radiologists achieved moderate reproducibility for PI-RADS version 2, and neither required nor benefitted from a training session. Agreement tended to be better in PZ than TZ, although was weak for DCE in PZ. The findings may help guide future PI-RADS lexicon updates. (©) RSNA, 2016 Online supplemental material is available for this article.
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Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB. Detection rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86, 38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset analysis of patients with normal DRE, csPCa detection was similar between two-core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%; p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes. Overall csPCa detection was similar between the MRI and control groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection. Our randomized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinically significant prostate cancer. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood. To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer. Prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the "gold standard." Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy. The primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score ≥ 4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy. Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P < .001) and 17% fewer low-risk cancers (213 vs 258 cases, P < .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P < .05 for all comparisons). Among men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy. clinicaltrials.gov Identifier: NCT00102544.
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The current diagnostic strategy using transrectal ultrasound-guided biopsy (TRUSGB) raises concerns regarding overdiagnosis and overtreatment of prostate cancer (PCa). Interest in integrating multiparametric magnetic resonance imaging (MRI) and magnetic resonance-guided biopsy (MRGB) into the diagnostic pathway to reduce overdiagnosis and improve grading is gaining ground, but it remains uncertain whether this image-based strategy is cost-effective. To determine the cost-effectiveness of multiparametric MRI and MRGB compared with TRUSGB. A combined decision tree and Markov model for men with elevated prostate-specific antigen (>4 ng/ml) was developed. Input data were derived from systematic literature searches, meta-analyses, and expert opinion. Quality-adjusted life years (QALYs) and health care costs of both strategies were modelled over 10 yr after initial suspicion of PCa. Probabilistic and threshold analyses were performed to assess uncertainty. Despite uncertainty around the presented cost-effectiveness estimates, our results suggest that the MRI strategy is cost-effective compared with the standard of care. Expected costs per patient were €2423 for the MRI strategy and €2392 for the TRUSGB strategy. Corresponding QALYs were higher for the MRI strategy (7.00 versus 6.90), resulting in an incremental cost-effectiveness ratio of €323 per QALY. Threshold analysis revealed that MRI is cost-effective when sensitivity of MRGB is ≥20%. The probability that the MRI strategy is cost-effective is around 80% at willingness to pay thresholds higher than €2000 per QALY. Total costs of the MRI strategy are almost equal with the standard of care, while reduction of overdiagnosis and overtreatment with the MRI strategy leads to an improvement in quality of life. We compared costs and quality of life (QoL) of the standard "blind" diagnostic technique with an image-based technique for men with suspicion of prostate cancer. Our results suggest that costs were comparable, with higher QoL for the image-based technique.
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Purpose The aim of this study was to assess the measurement properties of the 5-level classification system of the EQ-5D (5L), in comparison with the 3-level EQ-5D (3L). Methods Participants (n = 3,919) from six countries, including eight patient groups with chronic conditions (cardiovascular disease, respiratory disease, depression, diabetes, liver disease, personality disorders, arthritis, and stroke) and a student cohort, completed the 3L and 5L and, for most participants, also dimension-specific rating scales. The 3L and 5L were compared in terms of feasibility (missing values), redistribution properties, ceiling, discriminatory power, convergent validity, and known-groups validity. Results Missing values were on average 0.8 % for 5L and 1.3 % for 3L. In total, 2.9 % of responses were inconsistent between 5L and 3L. Redistribution from 3L to 5L using EQ dimension-specific rating scales as reference was validated for all 35 3L–5L-level combinations. For 5L, 683 unique health states were observed versus 124 for 3L. The ceiling was reduced from 20.2 % (3L) to 16.0 % (5L). Absolute discriminatory power (Shannon index) improved considerably with 5L (mean 1.87 for 5L versus 1.24 for 3L), and relative discriminatory power (Shannon Evenness index) improved slightly (mean 0.81 for 5L versus 0.78 for 3L). Convergent validity with WHO-5 was demonstrated and improved slightly with 5L. Known-groups validity was confirmed for both 5L and 3L. Conclusions The EQ-5D-5L appears to be a valid extension of the 3-level system which improves upon the measurement properties, reducing the ceiling while improving discriminatory power and establishing convergent and known-groups validity.
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To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen (PSA) testing; to assess early attitude to re-biopsy; to estimate healthcare resource use associated with adverse events due to biopsy; and to develop a classification scheme for reporting adverse events after prostate biopsy. Prospective cohort study (Prostate Biopsy Effects: ProBE) nested within Prostate Testing for Cancer and Treatment (ProtecT) study. Participants Between 1999 and 2008, 227,000 community dwelling men aged 50-69 years were identified at 352 practices and invited to counselling about PSA testing. 111,148 attended a nurse led clinic in the community, and 10,297 with PSA concentrations of 3-20 ng/mL were offered biopsy within ProtecT. Between February 2006 and May 2008, 1147/1753 (65%) eligible men (mean age 62.1 years, mean PSA 5.4 ng/mL) having 10 core transrectal ultrasound guided biopsy under antibiotic cover in the context of ProtecT were recruited to the ProBE study. Purpose designed questionnaire administered at biopsy and 7 and 35 days after the procedure to measure frequency and effect of symptoms related to pain, infection, and bleeding; patients' attitude to repeat biopsy assessed immediately after biopsy and 7 days later; participants' healthcare resource use within 35 days of biopsy evaluated by questionnaire, telephone follow-up, and medical note review; each man's adverse event profile graded according to symptoms and healthcare use. Pain was reported by 429/984 (43.6%), fever by 172/985 (17.5%), haematuria by 642/976 (65.8%), haematochezia by 356/967 (36.8%), and haemoejaculate by 605/653 (92.6%) men during the 35 days after biopsy. Fewer men rated these symptoms as a major/moderate problem-71/977 (7.3%) for pain, 54/981 (5.5%) for fever, 59/958 (6.2%) for haematuria, 24/951 (2.5%) for haematochezia, and 172/646 (26.6%) for haemoejaculate. Immediately after biopsy, 124/1142 (10.9%, 95% confidence interval 9.2 to 12.8) men reported that they would consider further biopsy a major or moderate problem: seven days after biopsy, this proportion had increased to 213/1085 (19.6%, 17.4% to 22.1%). A negative attitude to repeat biopsy was associated with unfavourable experience after the first biopsy, particularly pain at biopsy (odds ratio 8.2, P<0.001) and symptoms related to infection (7.9, P<0.001) and bleeding (4.2, P<0.001); differences were evident between centres (P<0.001). 119/1147 (10.4%, 8.7% to 12.3%) men reported consultation with a healthcare professional (usually their general practitioner), most commonly for infective symptoms. Complete data for all index symptoms at all time points were available in 851 participants. Symptoms and healthcare use could be used to grade these men as follows: grade 0 (no symptoms/contact) 18 (2.1%, 1.3% to 3.3%); grade 1 (minor problem/no contact) 550 (64.6%, 61.4% to 67.8%); grade 2 (moderate/major problem or contact) 271 (31.8%, 28.8% to 35.1%); grade 3 (hospital admission) 12 (1.4%, 0.8% to 2.4%); and grade 4 (death) 0. Grade of adverse event was associated with an unfavourable attitude to repeat biopsy (Kendall's τ-b ordinal by ordinal 0.29, P<0.001). This study with a high response rate of 89% at 35 days in men undergoing biopsy in the context of a randomised controlled trial has shown that although prostate biopsy is well tolerated by most men, it is associated with significant symptoms in a minority and affects attitudes to repeat biopsy and primary care resource use. These findings will inform men who seek PSA testing for detection of prostate cancer and assist their physicians during counselling about the potential risks and effect of biopsy. Variability in the adverse event profile between centres suggests that patients' outcomes could be improved and healthcare use reduced with more effective administration of local anaesthetic and antibiotics. Trial registration Current Controlled Trials ISRCTN20141297.
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This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument's sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording 'slight-moderate-severe' problems, with anchors of 'no problems' and 'unable to do' in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
Article
Background: Long-term psychological well-being and quality-of-life are important considerations when deciding whether to undergo active treatment for low-risk localised prostate cancer. Objective: To assess the long-term effects of active surveillance (AS) and/or watchful waiting (WW) on psychological and quality-of-life outcomes for low-risk localised prostate cancer patients. Design, setting, and participants: The Prostate Cancer Care and Outcome Study is a population-based prospective cohort study in New South Wales, Australia. Participants for these analyses were low-risk localised prostate cancer patients aged <70 yr at diagnosis and participated in the 10-yr follow-up. Outcome measurements and statistical analysis: Validated instruments assessed outcomes relating to six health-related quality-of-life and nine psychological domains relevant to prostate cancer patients. Adjusted mean differences (AMDs) in outcome scores between prostate cancer treatment groups were estimated using linear regression. Results and limitations: At 9-11 yr after diagnosis, patients who started AS/WW initially had (1) higher levels of distress and hyperarousal than initial radiation/high-dose-rate brachytherapy patients (AMD=5.9; 95% confidence interval or CI [0.5, 11.3] and AMD=5.4; 95% CI [0.2, 10.5], respectively), (2) higher levels of distress and avoidance than initial low-dose-rate brachytherapy patients (AMD=5.3; 95% CI [0.2, 10.3] and AMD=7.0; 95% CI [0.5, 13.5], respectively), (3) better urinary incontinence scores than initial radical prostatectomy patients (AMD=-9.1; 95% CI [-16.3, -2.0]), and (4) less bowel bother than initial radiation/high-dose-rate brachytherapy patients (AMD=-16.8; 95% CI [-27.6, -6.0]). No other significant differences were found. Limitations include participant attrition, inability to assess urinary voiding and storage symptoms, and nonrandom treatment allocation. Conclusions: Notwithstanding some long-term differences between AS/WW and various active treatment groups in terms of distress, hyperarousal, avoidance, urinary incontinence, and bowel bother, most long-term outcomes were similar between these groups. Patient summary: This study assessed the long-term psychological and quality-of-life impacts of initially monitoring rather than actively treating low-risk prostate cancer. The results suggest that initial monitoring rather than active treatment has only a minor impact on subsequent long-term psychological and quality-of-life outcomes.
Article
Background We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. Methods From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up). Results During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], −1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, −0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, −10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, −11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years. Conclusions After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression. (Funded by the Department of Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644.)
Article
Purpose of review: To review the role of prebiopsy multiparametric MRI in biopsy-naïve men for the detection of clinically significant prostate cancer. Recent findings: Recent level 1 evidence shows that multiparametric MRI has high sensitivity and negative predictive value for the detection of clinically significant prostate cancer in biopsy-naïve men. Concurrent developments include important work in the standardization of MRI reporting. The low specificity and positive predictive value of MRI means that biopsy is still necessary following MRI. MRI-targeted prostate biopsy has emerged as an alternative diagnostic test to transrectal ultrasound guided prostate biopsy, though its exact role in biopsy-naïve men and the optimal technique remain to be defined. Summary: There is the potential for MRI to be used as a triage test to allow a proportion of men to avoid biopsy and remain on prostate-specific antigen surveillance. MRI-suspicious areas can be sampled more intensively using MRI-targeted biopsy that can be carried out in a variety of ways. Future work should focus on the cost-effectiveness of introducing a prebiopsy MRI pathway in biopsy-naïve men and addressing the training needs for such a change. VIDEO ABSTRACT: http://links.lww.com/COU/A11.
Article
Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)
Article
Background: An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). Objective: To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Design, setting, and participants: Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). Intervention: In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. Outcomes measurements and statistical analysis: The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. Results and limitations: The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. Conclusions: A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. Patient summary: In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway.
Article
Introduction: Transrectal ultrasound-guided biopsy (TRUSGB) is the recommended approach to diagnose prostate cancer (PCa). Overdiagnosis and sampling errors represent major limitations. Magnetic resonance imaging (MRI)-targeted biopsy (MRTB) detects higher proportion of significant PCa and reduces diagnosis of insignificant PCa. Costs prevent MRTB from becoming the new standard in PCa diagnosis. The present study aimed at assessing whether added costs of MRI outweigh benefits of MRTB in a cost-utility model. Materials and methods: A Markov model was developed to estimate quality-adjusted life-year gained (QALY) and costs for 2 strategies (the standard 12-core TRUSGB strategy and the MRTB strategy) over 5, 10, 15, and 20 years. MRI was used as triage test in biopsy-naive men with clinical suspicion of PCa. The model takes into account probability of men harboring PCa, diagnostic accuracy of both procedures, and probability of being assigned to various treatment options. Direct medical costs based on health care system perspective were included. Results: Following standard TRUSGB pathway, calculated cumulative effects at 5, 10, 15, and 20 years were 4.25, 7.17, 9.03, and 10.09 QALY, respectively. Cumulative effects in MRTB pathway were 4.29, 7.26, 9.17, and 10.26 QALY, correspondingly. Costs related to TRUSGB strategy were $8,027, $11,406, $14,883, and $17,587 at 5, 10, 15, and 20 years, respectively, as compared with $7,231, $10,450, $13,267, and $15,400 for the MRTB strategy. At 5, 10, 15, and 20 years, MRTB was the established dominant strategy. Conclusions: Incorporation of MRI and MRTB in PCa diagnosis and management represents a cost-effective measure at 5, 10, 15, and 20 years after initial diagnosis.
Article
The Prostate Imaging - Reporting and Data System Version 2 (PI-RADS™ v2) is the product of an international collaboration of the American College of Radiology (ACR), European Society of Uroradiology (ESUR), and AdMetech Foundation. It is designed to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate multiparametric magnetic resonance imaging (mpMRI) examination, and it is based on the best available evidence and expert consensus opinion. It establishes minimum acceptable technical parameters for prostate mpMRI, simplifies and standardizes terminology and content of reports, and provides assessment categories that summarize levels of suspicion or risk of clinically significant prostate cancer that can be used to assist selection of patients for biopsies and management. It is intended to be used in routine clinical practice and also to facilitate data collection and outcome monitoring for research.
Article
Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Article
Multiparametric magnetic resonance imaging (MRI) of the prostate may improve the diagnostic accuracy of prostate cancer detection in MRI-targeted biopsy (MRI-TBx) in comparison to transrectal ultrasound-guided biopsy (TRUS-Bx). Systematic review and meta-analysis of evidence regarding the diagnostic benefits of MRI-TBx versus TRUS-Bx in detection of overall prostate cancer (primary objective) and significant/insignificant prostate cancer (secondary objective). A systematic review of Embase, Medline, Web of Science, Scopus, PubMed, Cinahl, and the Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies criteria. Only men with a positive MRI were included. The reports we included (16 studies) used both MRI-TBx and TRUS-Bx for prostate cancer detection. A cumulative total of 1926 men with positive MRI were included, with prostate cancer prevalence of 59%. MRI-TBx and TRUS-Bx did not significantly differ in overall prostate cancer detection (sensitivity 0.85, 95% confidence interval [CI] 0.80-0.89, and 0.81, 95% CI 0.70-0.88, respectively). MRI-TBx had a higher rate of detection of significant prostate cancer compared to TRUS-Bx (sensitivity 0.91, 95% CI 0.87-0.94 vs 0.76, 95% CI 0.64-0.84) and a lower rate of detection of insignificant prostate cancer (sensitivity 0.44, 95% CI 0.26-0.64 vs 0.83, 95% confidence interval 0.77-0.87). Subgroup analysis revealed an improvement in significant prostate cancer detection by MRI-TBx in men with previous negative biopsy, rather than in men with initial biopsy (relative sensitivity 1.54, 95% CI 1.05-2.57 vs 1.10, 95% CI 1.00-1.22). Because of underlying methodological flaws of MRI-TBx, the comparison of MRI-TBx and TRUS-Bx needs to be regarded with caution. In men with clinical suspicion of prostate cancer and a subsequent positive MRI, MRI-TBx and TRUS-Bx did not differ in overall prostate cancer detection. However, MRI-TBx had a higher rate of detection of significant prostate cancer and a lower rate of detection of insignificant prostate cancer compared with TRUS-Bx. We reviewed recent advances in magnetic resonance imaging (MRI) for guidance and targeting of prostate biopsy for prostate cancer detection. We found evidence to suggest that MRI-guided targeted biopsy benefits the diagnosis of prostate cancer. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Article
Increasing evidence supports the use of magnetic resonance (MR)-targeted prostate biopsy. The optimal method for such biopsy remains undefined, however. To prospectively compare targeted biopsy outcomes between MR imaging (MRI)-ultrasound fusion and visual targeting. From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences. Two MRI-ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy. Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression. Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum ≥7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting (p=0.1374, p=0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual (p=0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum ≥7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited. Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.
Article
BACKGROUND: A systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies. OBJECTIVE: To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING, AND PARTICIPANTS: Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist). RESULTS AND LIMITATIONS: The strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies. CONCLUSIONS: Use of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.
Article
Objective: Radical prostatectomy (RP) and radiation therapy are standard curative approaches for low-risk prostate cancer (PC). Active surveillance (AS) is becoming an increasingly accepted management alternative for low-risk PC. Our aim is to compare the cumulative medical costs of treatment vs. AS. Methods and materials: We collected data on the cumulative medical costs of open radical retropubic prostatectomy (RRP), robotic-assisted radical prostatectomy (RARP), external beam radiotherapy (EBRT), brachytherapy (BT), and AS at our institution. For physicians' reimbursements, Medicare values of our region were used to maintain uniformity. For inpatient costs other than reimbursements, we used the mean cost at our institution. The costs of RRP and RARP involve preoperative investigations, medical clearance, physicians' fees, inpatient costs, and pathologic examination of prostatectomy specimen and follow-up. The inpatient costs include the operating room, disposable equipment, anesthesia, post-anesthesia care, transfusion, and hospital stay. The cost of EBRT involves the cost of consultation, planning, simulation and treatment sessions, and follow-up. BT costs involved radiotherapy planning as well as inpatients costs. AS protocol involves regular visits, transrectal ultrasound guided biopsies, prostate specific antigen (PSA) testing. To evaluate the cost of treating complications, treatment after AS, and treatment for recurrence, we created a Markov model based on recent studies and our experience. Results: The cumulative costs of RRP are $9,732 (1 year), $10,360 (2 years), $12,209 (5 years), and $15,084 (10 years). While for RARP, the costs are $17,824 (1 year), $18,308 (2 years), $20,117 (5 years), and $22,762 (10 years). The costs of EBRT are $20,730 (1 year), $20,969 (2 years), $22,043 (5 years), and $23,953 (10 years). BT costs are $14,061 (1 year), $14,300 (2 years), $15,374 (5 years), and $17,284 (10 years). The costs of AS are $1,154 (1 year), $2,308 (2 years), $8,761 (5 years), and $13,116 (10 years). Conclusions: The cumulative medical costs of RARP and EBRT are much higher than BT, RRP, and AS. AS is associated with a different cost distribution in which the initial cost is low and relatively higher cost of follow-up. Despite the higher follow-up cost, AS remains the most cost effective alternative for low-risk PC.
Article
•To compare magnetic resonance imaging (MRI)-targeted biopsies with extended systematic biopsies for the detection of significant prostate cancer. •In all, 555 consecutive patients with suspicion of prostate cancer had pre-biopsy dynamic contrast-enhanced 1.5-tesla (T) MRI with pelvic coil, 10-12 transrectal ultrasound-guided extended systematic biopsies plus two targeted biopsies at any MRI area suspicious for malignancy. •Significant prostate cancer was defined as >5 mm total cancer length and/or any Gleason pattern >3. •Cancer length and grade at biopsy were reported and located on a 24-sector map. •Median (range) prostate-specific antigen (PSA) was 6.75 (0.18-100) ng/mL. •MRI was positive in 351 (63%) patients and, overall, 302 (54%) had cancer at extended systematic biopsies and/or targeted biopsies. Of 302 cancers detected, 249 (82%) were significant prostate cancers and 53 (18%) were nonsignificant prostate cancers. •Extended systematic biopsies did not detect 12 significant prostate cancers and targeted biopsies did not detect 13 significant prostate cancers. For significant prostate cancer detection, sensitivity, specificity and accuracy of targeted biopsies were 0.95, 1.0 and 0.98. The values for extended systematic biopsies were 0.95, 0.83, and 0.88. •The detection accuracy of significant prostate cancer by targeted biopsies was higher than that by extended systematic biopsies (P < 0.001). Targeted biopsies also detected 16% more grade 4/5 cases and better quantified the cancer than extended systematic biopsies, with cancer length of 5.56 vs. 4.70 mm (P= 0.002). • A targeted biopsies-only strategy without extended systematic biopsies would have necessitated a mean of 3.8 cores performed in only 63% of patients with positive MRI and avoided the potentially unnecessary diagnosis of 13% (53/302) of nonsignificant prostate cancers. • Strategy of targeted biopsies alone at pre-biopsy MRI-suspicious areas is an attractive potential alternative to extended systematic biopsies for detection of significant prostate cancer. •Further studies are necessary to validate the strategy of targeted biopsies alone.
Article
Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. Before the meeting, 520 items were scored for "appropriateness" by panel members, discussed face to face, and rescored. Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.
Article
We determined the value of mandatory second opinion pathology review to interpret prostate needle biopsy before radical prostatectomy. In all cases referred to our institution for radical prostatectomy in 1 year we compared pathological parameters in original and reviewed pathology reports, including benign, atypical or malignant diagnosis, final Gleason score, positive core number, core highest cancer percent and perineural invasion or extraprostatic extension. A major Gleason score discrepancy was defined as a change to a different risk category (6, 7 and 8-10). We defined a significant difference in the highest percent of cancer in a core as 30% or greater. Of the 855 cases originally diagnosed as prostatic adenocarcinoma cancer was confirmed in 844 (98.8%) by needle biopsy and prostatectomy, of which 9 (1%) were atypical and 2 (0.2%) were benign upon review. A major discrepancy in Gleason score was present in 124 cases (14.7%), of which 57 (46.0%) were upgraded and 67 (54%) were downgraded. Of cases with a final Gleason score of 6, 8.4% were originally diagnosed as 7 (7.8%) or 8-10 (0.6%), 21% with a final score of 7 had an original score of 6 (13.2%) or 8-10 (7.8%) and 21 of 61 (34%) with a score of 8-10 were originally diagnosed as 7 or less. There were 80 cases (64.5%) of disagreement between scores 6 and 7. Of the 777 cases with the positive core number in each report 71 (9.1%) had discrepancies. After review the positive core number was higher in 45 cases (63.4%) and lower in 26 (36.6%). We noted a significant difference in the highest cancer percent in a core in 76 of 844 evaluable cases (9%) in which cancer was originally underestimated. In 60 of 76 cases (78.9%) cancer discontinuously involved the core on review. Review revealed perineural invasion in 138 of 844 cases (16.3%) that was not originally reported in 37 of 138 (26.8%). In 4 cases review showed extraprostatic extension on needle biopsy. Compared to a smaller study more than 10 years ago at our institution the rate of unconfirmed cancer was identical (1.2%). To our knowledge this is the first study to analyze concordance upon review of the number of positive cores and maximum percent positive in a core (each discrepancy 9%). In a few cases mandatory second opinion on prostate needle biopsy results in significant differences that may affect therapy.
Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study
  • H U Ahmed
  • El-Shater
  • A Bosaily
  • L C Brown
Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017; 389: 815-22.
Comparing three different techniques for magnetic resonance imagingtargeted prostate biopsies: a systematic review of in-bore versus magnetic resonance imaging-transrectal ultrasound fusion versus cognitive registration -is there a preferred technique
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  • S Treweek
  • F Sullivan
  • P Donnan
  • K E Thorpe
  • M Zwarenstein
  • O Wegelin
  • Hhe Van Melick
  • L Hooft
Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015; 350: h2147. 25. Wegelin O, van Melick HHE, Hooft L, et al. Comparing three different techniques for magnetic resonance imagingtargeted prostate biopsies: a systematic review of in-bore versus magnetic resonance imaging-transrectal ultrasound fusion versus cognitive registration -is there a preferred technique? Eur Urol 2017; 71: 517-31.