Rationale and Objectives
We aimed to do a meta-analysis of the existing literature to assess the accuracy of prostate cancer (PCa) studies that use contrast-enhanced ultrasound (CEUS) as a diagnostic tool.
Materials and Methods
The MEDLINE, EMBASE, and Cochrane Library databases were searched for relevant original articles published up to August 2012. Characteristics of Included studies were recorded. Methodological quality was assessed by using the quality assessment of diagnostic studies tool. Pooled weighted estimates of diagnostic odds ratio (DOR), sensitivity, specificity, and positive and negative likelihood ratio (LR) were calculated. A summary receiver operator characteristic (SROC) curve was constructed to calculate the area under the curve (AUC). Publication bias analysis was also performed.
Results
Sixteen studies (2624 patients) were included in the meta-analysis. Various contrast agents and imaging modes were applied. The independent random-effects summary showed a variation in diagnostic values. The summary estimates of sensitivity, specificity, and DOR were 0.70, 0.74, and 9.09, respectively. The weighted positive and negative LR were 2.81 and 0.35, with statistically significant between-study heterogeneity ( P < .001). Sensitivity was better in positive patient studies than positive biopsy cores ones (0.78 vs. 0.64). SROC plot displayed value for AUC (0.82). Begg’s test ( P = .822) and Egger’s test ( P = .198) did not show evidence of publication bias.
Conclusion
CEUS is a promising tool in the detection of PCa, but it cannot completely replace systematic biopsy under the present circumstances. It is necessary to standardize imaging techniques, contrast agents and diagnostic criteria. Large samples, multi-center studies and high-quality prospective trials are necessary to assess its clinical value.
Introduction
Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males. The American Cancer Society estimates that in 2012 PCa will account for 29% of new cancer diagnoses in men and 9% of cancer-related deaths in the United States . Early detection is the key to successful treatment. Digital rectal examination, prostate-specific antigen, conventional transrectal ultrasonography, and magnetic resonance imaging have been the main methods for detecting PCa. These methods are available but the diagnosis of PCa is far from optimal . Grayscale transrectal ultrasound-guided systematic biopsy is the reference standard method, however, it has been shown that this approach missed clinically relevant cancers. Autopsy studies have demonstrated that sensitivity of sextant prostate biopsy was 30%, with increasing sensitivity with increasing numbers of biopsy cores, 36%–58% for 12-core biopsies, and 53%–58% for 18-core biopsies . PCa is multifocal and heterogeneous in nature, making it difficult to detect all cancers, sites, and grades . Thus, new techniques that help us to display more cancerous lesions and to target areas of high cancer incidence are desirable.
Contrast-enhanced ultrasound (CEUS) imaging was developed to real-time image perfusion . Ultrasound contrast agents consist of small encapsulated gas bubbles that are administered intravenously and remain intravascular. Adding microbubbles as additional reflectors into the bloodstream increase the sensitivity of imaging. Numerous studies have been performed to assess the diagnostic performance of CEUS in the evaluation of prostate lesions . These studies yield varying estimates of sensitivity and specificity, which are probably caused by advances in technology, differences in scan protocols, and heterogeneity in patient populations. The purpose of our study, therefore, was to perform a systematic review and quantitative meta-analysis of the literature to determine the overall diagnostic value of CEUS for PCa.
Materials and methods
Data Sources and Exclusion Criteria
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Quality Assessment and Data Extraction
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Data Synthesis and Statistical Analysis
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Results
Study Selection and Characteristics
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Table 1
Characteristics of Included Studies
Author, Publication Year (Reference) Country No. of Patients Study Design Mean Patient Age (y) Contrast Agent Gold Standard Mean PSA (ng/mL) Volume of Prostate (mL) QUADAS Score Bogers et al, 1999 Netherlands 18 Retrospective NR Levovist® Biopsy 18.6 NR 11 Frauscher et al, 2002 Austria 230 Prospective 56.0 Levovist® Biopsy 4.6 NR 13 Halpern et al, 2001 United States 60 Prospective 64.0 Definity® Biopsy NR NR 12 Halpern et al, 2005 United States 301 NR 63.0 AF0150 Biopsy 9.5 NR 13 Karaman et al, 2005 Turkey 32 Prospective 63.5 Levovist® Biopsy 9.5 48.0 13 Mitterberger et al, 2010 Austria 760 NR 60.9 Sulfur hexafluoride Biopsy 4.5 43.0 12 Morelli et al, 2011 Italy 150 Prospective 65.0 SonoVue® Biopsy 8.2 NR 13 Pelzer et al, 2005 Austria 380 NR 60.7 SonoVue® Biopsy 6.2 35.5 13 Roy et al, 2003 France 85 NR 64.0 NR Biopsy 18.2 NR 12 Seitz et al, 2011 Germany 35 Prospective 64.0 SonoVue® Prostatectomy 12.7 NR 13 Taymoorian et al, 2007 Germany 95 Prospective 66.0 SonoVue® Biopsy 10.0 50.0 13 Unal et al, 2000 Netherlands 59 Retrospective 64.9 Levovist Prostatectomy 10.1 45.8 11 Xie et al, 2011 China 150 Prospective 68.5 SonoVue® Biopsy 22.1 54.4 13 Yang et al, 2008 China 115 Prospective 70.0 SonoVue® Biopsy NR NR 13 Yi et al, 2006 Korea 48 Prospective 62.0 Levovist® Biopsy 7.5 NR 11 Zhao et al, 2011 China 106 NR 68.7 SonoVue® Biopsy 10.1 53.9 12
NR, not reported.
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Methodologic Quality Assessment
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Pooled Estimates
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Heterogeneity and Meta-regression Analysis
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Publication Bias
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Discussion
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Conclusions
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