Original article
Contrast-enhanced transrectal ultrasound (CE-TRUS) with cadence-contrast pulse sequence (CPS) technology for the identification of prostate cancer

https://doi.org/10.1016/j.urolonc.2009.03.032Get rights and content

Abstract

Objectives

Various imaging modalities, such as magnetic resonance imaging (MRI), have been assessed with regard to their value in the detection of prostate cancer (CaP). However, there is a need for less time-consuming and more cost effective procedures in urology. In order to determine the ability of contrast-enhanced transrectal ultrasound (CE-TRUS) to identify CaP, we investigated patients scheduled for radical prostatectomy for CaP and radical cystoprostatectomy for bladder cancer.

Material and methods

Between May and August 2008, 35 consecutive patients with CaP and muscle-invasive bladder carcinoma were prospectively enrolled in this single center study. All patients underwent B-mode TRUS and CE-TRUS (Sequoia 512 unit with an endocavity probe EV8C4, 8 MHz; Siemens, Erlangen, Germany) by one investigator blinded to any clinical data before radical surgery. Contrast-enhanced images were obtained after intravenous infusion of a bolus (2.4 ml) of the contrast agent SonoVue (Bracco, Milan, Italy). Ultrasound findings (CE-TRUS and B-mode TRUS) were correlated with step-section histology.

Results

On a per-patient basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting CaP with CE-TRUS were 71.0%, 50.0%, 91.7%, and 18.2%, respectively. In comparison with B-mode TRUS (sensitivity 45.2%, specificity 75.0%, PPV 93.3%, and NPV 18.0%), CE-TRUS performed significantly better (P = 0.004, McNemar test). On a per-prostate-lobe basis sensitivity, specificity, PPV, and NPV were 69.0%, 33.3%, 83.3%, and 18.2%.

Conclusion

CE-TRUS detected prostate cancer with a modest sensitivity and a high PPV in a selected patient cohort. Future randomized-controlled multicenter studies are needed to further validate the value of CE-TRUS in the detection of CaP. Based on our results, CE-TRUS may not be recommended as a routine procedure in the diagnosis of CaP at present.

Introduction

Despite advances in prostate cancer (CaP) detection and treatment, the disease continues to represent an enormous healthcare burden. Among men in the European Union, CaP accounts for approximately 11% of all cancers and 9% of all cancer deaths [1]. The diagnosis of CaP is based on a combination of digital rectal examination (DRE), serum prostate-specific antigen (PSA) testing, and transrectal ultrasound (TRUS)-guided biopsy. TRUS, although the most commonly used imaging modality, has sensitivities for diagnosing prostate cancer of 17%–57% and specificities of 40%–63%, with accuracies of 58%–90% [2]. Published data on extracapsular extension (ECE) and seminal vesicle invasion (SVI) vary with accuracies of 58%–86% and 78%, sensitivities of 50%–90% and 22%–60%, and specificities of 46%–91% and 78%, respectively [3], [4], [5]. In contrast, a multi-institutional study with 386 patients and another study with 558 patients comparing TRUS and DRE revealed that there was no clinically important superiority of TRUS over DRE alone [6]. Consequently, new strategies for prostate cancer detection have been evaluated. Magnetic resonance imaging (MRI) techniques with and without endorectal coil, such as magnetic resonance spectroscopy imaging (MRSI), diffusion-weighted MRI (DW-MRI), and dynamic contrast-enhanced MRI (DCE-MRI) with field strength up to 3 Tesla, have shown sensitivities in the detection of CaP of 42%–93% with specificities of 81%–89% [7], [8], [9], [10], [11]. On the other hand, cost and time pressure in the healthcare system will prevent a wide implementation of these innovative MRI techniques. Therefore, several groups have been evaluating ultrasound-based new technologies, such as contrast-enhanced TRUS (CE-TRUS) and elastography [12], [13], [14]. While ultrasound-based elastography discriminates hard (solid tumor) from adjacent soft tissue (benign tissue), CE-TRUS reveals the vascular pattern of individual microvessels. Preliminary investigations suggest that employing ultrasound contrast agents (second generation) using cadence-contrast pulse sequencing (CPS) or microflow imaging (MFI) technology enhances the visualization of tumor vascularity in CaP [12], [14], [15], [16].

In an attempt to evaluate its value in the detection of CaP in a prostate biopsy setting, several studies have been carried out with CE-TRUS. Although microflow imaging seems to be a promising tool in increasing the efficacy of detecting prostatic carcinoma, data were based on prostate biopsy as reference standard. Therefore, the aim of this study was to assess the value of CE-TRUS using CPS technology for identifying CaP in a cohort of patients scheduled for radical prostatectomy (rPx) for CaP or cystoprostatectomy (rCx) for bladder cancer by comparing the results of CE-TRUS with second-generation microbubble contrast agent (SonoVue, Bracco, Milan, Italy) to complete prostate specimen.

Section snippets

Materials and methods

Between May and August 2008, a total of 35 consecutive patients scheduled for rPx and rCx (T2 transitional cell carcinoma based on histology and CT-scan), who were eligible for the study, had CE-TRUS before surgery in this prospective, single-institution, single-observer study. CE-TRUS was performed by one urologist with experience of more than 5,000 transrectal ultrasound examinations and experience in contrast enhanced ultrasound of renal and prostatic disease. The interval between prostate

Results

Overall, in the prostate carcinoma group the mean serum PSA level was 13.9 ng/ml (SD ± 6.0), the mean Gleason score was 6.7 (SD ± 0.7), and the mean age 62.8 years (SD ± 6.9), while patients with transitional cell carcinoma of the urinary bladder (TCC-group) had a mean serum PSA level of 5.4 ng/ml (SD ± 2.0), and a mean age 71.4 years (SD ± 3.4). The mean size of index tumor was 1.2 ccm (SD ± 0.6). No side effect (reactions at the injection site, headache, nausea) was noted in study population.

Discussion

Gray-scale TRUS was not proven to be satisfactory for local staging of prostate cancer. Due to a low sensitivity and specificity for visualization of CaP, it is generally acknowledged that TRUS is of limited value [17], [18]. Therefore, systematic, randomized TRUS-guided biopsy is still the gold standard for CaP detection [1]. Ambiguous efforts are being made to improve the detection yield. Recently, extended protocols have been advocated, which include 6 standard sextant biopsies, with

Conclusion

In conclusion, CE-TRUS enables a visualization of the microvasculature of the prostate. Although, CE-TRUS seems to have a fairly good sensitivity and a high PPV in identifying CaP in a pre-selected patient cohort, it must be taken into account that these are preliminary data and that the number of patients in our study was limited. Therefore, future randomized-controlled multicenter studies are needed to assess the value of CE-TRUS in the detection of prostate cancer. At present, CE-TRUS cannot

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    These authors contributed equally to this work.

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