Elsevier

Academic Radiology

Volume 20, Issue 2, February 2013, Pages 156-164
Academic Radiology

Original investigation
Diagnostic Performance of Contrast Enhanced Ultrasound in Patients with Prostate Cancer: A Meta-Analysis

https://doi.org/10.1016/j.acra.2012.09.018Get rights and content

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 (1). 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 2, 3. 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 (4). PCa is multifocal and heterogeneous in nature, making it difficult to detect all cancers, sites, and grades (5). 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 6, 7. 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 (8). 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.

Section snippets

Data Sources and Exclusion Criteria

This study was approved by the Ethics Committee of our institution. The systematic review and meta-analysis was performed according to the recently published recommendations and checklist of the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (9). Literature searches were conducted on MEDLINE, EMBASE, and COCHRANE databases for publications up to August 2012. The search strategy, which included the use of both pertinent Medical Subject Headings, or MeSH, and free

Study Selection and Characteristics

By using the search terms described earlier, we identified 405 studies. One hundred and twelve studies were excluded because of overlap between the MEDLINE and EMBASE databases. Our search excluded 201 studies based on the title and abstract. Forty-four citations were excluded because of a lack of original data. Forty-eight citations were then retrieved for full text review. Thirty-two were excluded because of lack of control subjects or portion of data have been published previously. After

Discussion

Meta-analysis is a statistical analysis that combines or integrates the results of several independent studies (33). Using meta-analysis is possible to explain variations in study results and additionally may be used to highlight important defects in the quality of primary studies and to identify areas of future research 34, 35. The reliability of the results depends on the quality of the included studies and whether the result of the analysis is reliable. Our review was based on thorough

Conclusions

In summary, this systematic review describes the diagnostic test performance of CEUS for detection of PCa. Our results suggested that CEUS can be used as a diagnostic method in patients suspected of PCa. But it should not be used as sole biopsy guidance and cannot completely replace systematic biopsy under the present circumstances. Reliability of CEUS is not only dependent on diagnostic criteria, but also the training and expertise of operators. We realize it is necessary to standardize

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    Supported by grants from the National Natural Science Foundation of China (No. 81000619) and the Nursery Foundation of Chinese PLA general hospital (No. 10KMM37).

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