Magnetic resonance imaging (MRI), with or without MRI-targeted biopsy (MRI pathway), is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate ...cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision making.
To determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, MRI pathway, and systematic biopsy, as compared with template-guided biopsy (reference standard), in detecting clinically significant prostate cancer, defined as International Society of Urological Pathology grade 2 or higher, in biopsy-naive men or those with a prior-negative biopsy (or mix of both).
We systematically searched the literature and considered for inclusion any cross-sectional study if it investigated (1) one or more index tests verified by the reference standard, and (2) paired testing of the MRI pathway with systematic biopsy. Quality and certainty of evidence were assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation, respectively.
Accuracy analyses: Using a baseline cancer prevalence of 30%, MRI pathway (sensitivity 0.72 95% confidence interval {CI}: 0.60–0.82; specificity 0.96 0.94–0.98; eight studies) may result in 216 (180–246) true positives, 28 (14–42) false positives, 672 (658–686) true negatives, and 84 (54–120) false negatives per 1000 men. Systematic biopsy (sensitivity 0.63 0.19–0.93; specificity 1.00 0.91–1.00; four studies) may result in 189 (57–279) true positives, 0 (0–63) false positives, 700 (637–700) true negatives, and 111 (21–243) false negatives per 1000 men. Agreement analyses: With a direct comparison of the MRI pathway with systematic biopsy concerning significant disease, we found pooled detection ratios of 1.05 (95% CI: 0.95–1.16; 20 studies) in biopsy-naive men and 1.44 (1.19–1.75; 10 studies) in men with a prior-negative biopsy. Concerning insignificant disease, we found detection ratios of 0.63 (95% CI: 0.54–0.74), and 0.62 (95% CI: 0.44–0.88), respectively.
MRI pathway had the most favourable outcome in significant and insignificant prostate cancer detection compared with systematic biopsy. The certainty in our findings was reduced by study limitations.
We reviewed recent advances in prostate biopsy by magnetic resonance imaging (MRI) guidance and targeting for prostate cancer detection in comparison with standard diagnosis by systematic biopsies. The findings of this Cochrane review suggest that MRI pathway is better than systematic biopsies in making a correct diagnosis of clinically important prostate cancer and reducing redundant biopsies and the detection of unimportant cancers substantially. However, MRI pathway still misses some men with important prostate cancer. Therefore, further research in this area is important.
In all men suspected to have clinically significant prostate cancer, the magnetic resonance imaging (MRI) pathway, including prostate MRI and MRI-targeted biopsy, may represent a more favourable diagnostic test than systematic biopsy, which is the current standard practice. Therefore, performing prostate MRI before any biopsy should be structurally incorporated in the diagnostic work-up.
Background
Multiparametric magnetic resonance imaging (MRI), with or without MRI‐targeted biopsy, is an alternative test to systematic transrectal ultrasonography‐guided biopsy in men suspected of ...having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence‐based decision‐making.
Objectives
To determine the diagnostic accuracy of the index tests MRI only, MRI‐targeted biopsy, the MRI pathway (MRI with or without MRI‐targeted biopsy) and systematic biopsy as compared to template‐guided biopsy as the reference standard in detecting clinically significant prostate cancer as the target condition, defined as International Society of Urological Pathology (ISUP) grade 2 or higher. Secondary target conditions were the detection of grade 1 and grade 3 or higher‐grade prostate cancer, and a potential change in the number of biopsy procedures.
Search methods
We performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.
Selection criteria
We considered for inclusion any cross‐sectional study if it investigated one or more index tests verified by the reference standard, or if it investigated the agreement between the MRI pathway and systematic biopsy, both performed in the same men. We included only studies on men who were biopsy naïve or who previously had a negative biopsy (or a mix of both). Studies involving MRI had to report on both MRI‐positive and MRI‐negative men. All studies had to report on the primary target condition.
Data collection and analysis
Two reviewers independently extracted data and assessed the risk of bias using the QUADAS‐2 tool. To estimate test accuracy, we calculated sensitivity and specificity using the bivariate model. To estimate agreement between the MRI pathway and systematic biopsy, we synthesised detection ratios by performing random‐effects meta‐analyses. To estimate the proportions of participants with prostate cancer detected by only one of the index tests, we used random‐effects multinomial or binary logistic regression models. For the main comparisions, we assessed the certainty of evidence using GRADE.
Main results
The test accuracy analyses included 18 studies overall.
MRI compared to template‐guided biopsy: Based on a pooled sensitivity of 0.91 (95% confidence interval (CI): 0.83 to 0.95; 12 studies; low certainty of evidence) and a pooled specificity of 0.37 (95% CI: 0.29 to 0.46; 12 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI may result in 273 (95% CI: 249 to 285) true positives, 441 false positives (95% CI: 378 to 497), 259 true negatives (95% CI: 203 to 322) and 27 (95% CI: 15 to 51) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.
MRI‐targeted biopsy compared to template‐guided biopsy: Based on a pooled sensitivity of 0.80 (95% CI: 0.69 to 0.87; 8 studies; low certainty of evidence) and a pooled specificity of 0.94 (95% CI: 0.90 to 0.97; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI‐targeted biopsy may result in 240 (95% CI: 207 to 261) true positives, 42 (95% CI: 21 to 70) false positives, 658 (95% CI: 630 to 679) true negatives and 60 (95% CI: 39 to 93) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.
The MRI pathway compared to template‐guided biopsy: Based on a pooled sensitivity of 0.72 (95% CI: 0.60 to 0.82; 8 studies; low certainty of evidence) and a pooled specificity of 0.96 (95% CI: 0.94 to 0.98; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, the MRI pathway may result in 216 (95% CI: 180 to 246) true positives, 28 (95% CI: 14 to 42) false positives, 672 (95% CI: 658 to 686) true negatives and 84 (95% CI: 54 to 120) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations, inconsistency and imprecision.
Systemic biopsy compared to template‐guided biopsy: Based on a pooled sensitivity of 0.63 (95% CI: 0.19 to 0.93; 4 studies; low certainty of evidence) and a pooled specificity of 1.00 (95% CI: 0.91 to 1.00; 4 studies; low certainty of evidence) using a baseline prevalence of 30%, systematic biopsy may result in 189 (95% CI: 57 to 279) true positives, 0 (95% CI: 0 to 63) false positives, 700 (95% CI: 637 to 700) true negatives and 111 (95% CI: 21 to 243) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.
Agreement analyses: In a mixed population of both biopsy‐naïve and prior‐negative biopsy men comparing the MRI pathway to systematic biopsy, we found a pooled detection ratio of 1.12 (95% CI: 1.02 to 1.23; 25 studies). We found pooled detection ratios of 1.44 (95% CI 1.19 to 1.75; 10 studies) in prior‐negative biopsy men and 1.05 (95% CI: 0.95 to 1.16; 20 studies) in biopsy‐naïve men.
Authors' conclusions
Among the diagnostic strategies considered, the MRI pathway has the most favourable diagnostic accuracy in clinically significant prostate cancer detection. Compared to systematic biopsy, it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed. The certainty in our findings was reduced by study limitations, specifically issues surrounding selection bias, as well as inconsistency. Based on these findings, further improvement of prostate cancer diagnostic pathways should be pursued.
Objectives
To investigate whether serial prostate magnetic resonance imaging (MRI) may guide the utility of repeat targeted (TBx) and systematic biopsy (SBx) when monitoring men with low‐risk ...prostate cancer (PCa) at 1‐year of active surveillance (AS).
Patients and Methods
We retrospectively included 111 consecutive men with low‐risk (International Society of Urological Pathology ISUP Grade 1) PCa, who received protocolled repeat MRI with or without TBx and repeat SBx at 1‐year of AS. TBx was performed in Prostate Imaging‐Reporting and Data System (PI‐RADS) score ≥3 lesions (MRI‐positive men). Upgrading defined as ISUP Grade ≥2 PCa (I), Grade ≥2 with cribriform growth/intraductal carcinoma PCa (II), and Grade ≥3 PCa (III) was investigated. Upgrading detected by TBx only (not by SBx) and SBx only (not by TBx) was investigated in MRI‐positive and ‐negative men, and related to radiological progression on MRI (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation PRECISE score).
Results
Overall upgrading (I) was 32% (35/111). Upgrading in MRI‐positive and ‐negative men was 48% (30/63) and 10% (5/48) (P < 0.001), respectively. In MRI‐positive men, there was upgrading in 23% (seven of 30) by TBx only and in 33% (10/30) by SBx only. Radiological progression (PRECISE score 4–5) in MRI‐positive men was seen in 27% (17/63). Upgrading (I) occurred in 41% (seven of 17) of these MRI‐positive men, while this was 50% (23/46) in MRI‐positive men without radiological progression (PRECISE score 1–3) (P = 0.534). Overall upgrading (II) was 15% (17/111). Upgrading in MRI‐positive and ‐negative men was 22% (14/63) and 6% (three of 48) (P = 0.021), respectively. In MRI‐positive men, there was upgrading in three of 14 by TBx only and in seven of 14 by SBx only. Overall upgrading (III) occurred in 5% (five of 111). Upgrading in MRI‐positive and ‐negative men was 6% (four of 63) and 2% (one of 48) (P = 0.283), respectively. In MRI‐positive men, there was upgrading in one of four by TBx only and in two of four by SBx only.
Conclusion
Upgrading is significantly lower in MRI‐negative compared to MRI‐positive men with low‐risk PCa at 1‐year of AS. In serial MRI‐negative men, the added value of repeat SBx at 1‐year surveillance is limited and should be balanced individually against the harms. In serial MRI‐positive men, the added value of repeat SBx is substantial. Based on this cohort, SBx is recommended to be performed in combination with TBx in all MRI‐positive men at 1‐year of AS, also when there is no radiological progression.
Objectives
To assess the value of risk‐stratification based on magnetic resonance imaging (MRI) and prostate‐specific antigen density (PSA‐D) in reducing unnecessary biopsies without missing Gleason ...pattern 4 prostate cancer in men on active surveillance (AS).
Patients and Methods
In all, 210 men on AS with Gleason score 3 + 3 prostate cancer received a first MRI and if indicated Prostate Imaging Reporting and Data System (PI‐RADS) score ≥3 targeted biopsy (TBx) using MRI‐transrectal ultrasonography (TRUS) fusion. The MRI was performed 3 months after diagnosis (group A: n = 97), at confirmatory biopsy (group B: n = 39) or at surveillance biopsy after one or more repeat TRUS‐guided systematic biopsies (TRUS‐Bx) (group C: n = 74). The primary outcome was upgrading to Gleason score ≥3 + 4 prostate cancer based on MRI ± TBx in groups A, B and C. Biopsy outcomes were stratified for the overall PI‐RADS score and PSA‐D to identify a subgroup of men in whom a biopsy could have been avoided as no Gleason score upgrading was detected.
Results
In all, 134/210 (64%) men had a positive MRI and 51/210 (24%) men had Gleason score upgrading based on MRI‐TBx. The percentage of Gleason score upgrading based on MRI‐TBx was 23% (22/97), 23% (9/39) and 27% (20/74) in respectively groups A, B and C. Additional Gleason score upgrading detected by TRUS‐Bx occurred in 8% (3/39) of men in group B and 6% (1/17) of men who received TRUS‐Bx in group C. No Gleason score upgrading was detected by MRI‐TBx in men with a PI‐RADS score of 3 and a PSA‐D of <0.15 ng/mL2(n = 15), nor by TRUS‐Bx in men with a PI‐RADS score of 1–3 and a PSA‐D of <0.15 ng/mL2 (n = 15).
Conclusion
At least one out of five men on AS with Gleason score 3 + 3 prostate cancer at diagnostic TRUS‐Bx show Gleason score upgrading based on first MRI ± TBx at baseline, confirmatory or surveillance biopsy. Men with a PI‐RADS score of 1–3 and PSA‐D of <0.15 ng/mL2 did not show Gleason score upgrading at MRI ± TBx or TRUS‐Bx at each time point of surveillance. Thus risk‐stratification based on PI‐RADS and PSA‐D may reduce unnecessary follow‐up biopsy procedures in men on AS.
The role and ethics of professionals in business and economics have been questioned, especially after the financial crisis of 2008. Some suggest a reorientation using concepts such as craftsmanship. ...In this article, I will explore professional practices within the context of behavioural theory and business ethics. I suggest that scholars of behavioural theory need a strategy to deal with normative questions to meet their ambition of practical relevance. Evidence-based management (EBMgt), a recent behavioural approach, may assist business ethics scholars in understanding how professionals infer 'evidence' to make decisions. For a professional, ethical issues are an integral part of decision-making at critical moments. As reflective practitioners, they develop insights related to ethical concerns when collecting and assessing evidence within decision-making processes.
SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project ...was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex‐differences. METHODS AND RESULTS: In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration–time curve (AUC), the micronized curcumin was 14‐, 5‐, and 9‐fold and micellar curcumin 277‐, 114‐, and 185‐fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. CONCLUSION: Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
Abstract Prenylated chalcones and flavonoids gained increasing attention not only in nutrition but also in cancer prevention because of their biological and molecular activities in humans, which have ...been extensively investigated in vitro or in preclinical studies. These naturally occurring compounds exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display antiinflammatory properties. In particular, their potential to prevent proliferation of tumor cells is noteworthy. Some representatives of this subclass of secondary plant compounds exert pronounced anti–tumor-initiating capacities and directly inhibit growth of cancer cells, whereas their toxic effects on healthy tissues are remarkably low. These promising pharmacologic characteristics are countered by low ingestion, low bioavailability, and little knowledge of their metabolism. This review focuses on the great potential of these plant- and nutrient-derived compounds for cancer prevention and therapy. Provided here is a comprehensive summary of the current knowledge and inherent modes of action, focusing on the prenylated chalcones xanthohumol, desmethylxanthohumol, and xanthogalenol, as well as the prenylated flavonoids isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin, 6-geranylnaringenin, 8-geranylnaringenin, and pomiferin.
Newly developed protein drugs that target tumor‐associated antigens are often modified in order to increase their therapeutic effect, tumor exposure, and safety profile. During the development of ...protein drugs, molecular imaging is increasingly used to provide additional information on their in vivo behavior. As a result, there are increasing numbers of studies that demonstrate the effect of protein modification on whole body distribution and tumor uptake of protein drugs. However, much still remains unclear about how to interpret obtained biodistribution data correctly. Consequently, there is a need for more insight in the correct way of interpreting preclinical and clinical imaging data. Summarizing the knowledge gained to date may facilitate this interpretation. This review therefore provides an overview of specific protein properties and modifications that can affect biodistribution and tumor uptake of anticancer antibodies, antibody fragments, and nonimmunoglobulin scaffolds. Protein properties that are discussed in this review are molecular size, target interaction, FcRn binding, and charge. Protein modifications that are discussed are radiolabeling, fluorescent labeling drug conjugation, glycosylation, humanization, albumin binding, and polyethylene glycolation.
When corporate social responsibility (CSR) as a sensemaking process is assessed from a corporate governance perspective, this implies that stakeholders do not only influence companies by promoting ...and enforcing regulations and other corporate guidelines. They also influence companies by promoting regulation on influence pathways, by demanding that companies develop formal mechanisms that allow companies and stakeholders to discuss and in some cases agree on changes to principles and policies. This perspective suggests that regulation is an outcome of power relations and is, as such, a reflection of certain mental models. As such, mental models reveal the political bias in corporate governance perspectives. For this reason, CSR research needs to be clear about the underlying assumptions about corporate governance, and corporate governance research needs to disclose which mental models of CSR influence the outcomes. Taking a governance perspective on the development of mental models of CSR helps to understand the interaction between CSR and processes of sensemaking at the institutional, organizational and individual levels.
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