The value of contrast-enhanced ultrasound and magnetic resonance imaging in the diagnosis of bladder cancer

Cheng Li; Zhuoran Gu; Peiqian Ni; Wentao Zhang; Fuhan Yang; Wei Li; Xudong Yao; Yifan Chen

doi:10.4103/jcrt.jcrt_1056_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 17 | Issue : 5 | Page : 1179-1185

The value of contrast-enhanced ultrasound and magnetic resonance imaging in the diagnosis of bladder cancer

Cheng Li¹, Zhuoran Gu¹, Peiqian Ni¹, Wentao Zhang¹, Fuhan Yang¹, Wei Li¹, Xudong Yao², Yifan Chen¹
¹ Department of Urology, Shanghai Tenth People's Hospital; Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
² Department of Urology, Shanghai Tenth People's Hospital; Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai; Shanghai Clinical College, Anhui Medical University, Hefei, China

Date of Submission	02-Jul-2021
Date of Acceptance	21-Sep-2021
Date of Web Publication	27-Nov-2021

Correspondence Address:
Wei Li
Department of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Jingan District, Shanghai 200072
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcrt.jcrt_1056_21

> Abstract

Objective: Imaging examination, tumor marker detection, bladder biopsy, and other methods are the common methods for the diagnosis of bladder cancer (BC). This study was aimed to assess the value of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of BC.
Materials and Methods: Fifty-nine patients with BC were recruited in our hospital from September 2012 to December 2015, who had CEUS and magnetic resonance diffusion-weighted imaging (MRI + DWI). All patients underwent surgical treatment and definite pathological stage. The series and parallel combined diagnosis methods were applied to calculate the diagnostic sensitivity, specificity, and accuracy through using quantitative apparent diffusion coefficient (ADC) and receiver operating characteristic curve.
Results: The accuracies of CEUS and MRI + DWI examination for T staging of BC were 74.6% and 76.3%, respectively. Compared with the single diagnostic methods, the two combined diagnosis accuracy was 91.5%, which was significantly improved in diagnosis accuracy (P < 0.05). The diagnostic accuracies of CEUS, MRI + DWI, and ADC for muscle invasion of BC were 81.4%, 83.1%, and 84.7%, respectively. The diagnostic accuracy of CEUS parallel combined with MRI + DWI (91.5%) was obviously enhanced, compared with that with the single diagnostic method.
Conclusion: The accuracy of CEUS and MRI + DWI combined diagnosis was higher than that with the single diagnostic method. CEUS and MRI + DWI combined diagnosis was a feasible and effective method for the clinical diagnosis of BC.

Keywords: Bladder cancer, contrast-enhanced ultrasonography, magnetic resonance diffusion-weighted imaging

How to cite this article:
Li C, Gu Z, Ni P, Zhang W, Yang F, Li W, Yao X, Chen Y. The value of contrast-enhanced ultrasound and magnetic resonance imaging in the diagnosis of bladder cancer. J Can Res Ther 2021;17:1179-85

How to cite this URL:
Li C, Gu Z, Ni P, Zhang W, Yang F, Li W, Yao X, Chen Y. The value of contrast-enhanced ultrasound and magnetic resonance imaging in the diagnosis of bladder cancer. J Can Res Ther [serial online] 2021 [cited 2023 Jan 27];17:1179-85. Available from: https://www.cancerjournal.net/text.asp?2021/17/5/1179/331300

> Introduction

Bladder cancer (BC) is one of the most common malignant tumors in genitourinary system. In Europe, the United States, and other Western countries, the incidence rate of BC ranked seventh in male malignant tumors whereas ranked after the tenth in females during the period of 2005–2009. According to statistical data from the American Cancer Society, the male BC incidence rate is about 37.5/100 and female incidence rate is about 9.3/10 million in the United States.^[1] Moreover, the American Cancer Society estimated that, in 2013, 72,570 new cases of BC occurred in the United States, of which 15210 cases died.^[2]

Actually, in China, the incidence of BC is lower than that in Europe, the United States, and other developed countries. However, the incidence tends to rise in recent years, and the incidence of Chinese males has reached 11.41/10 million in 2009, while the incidence rate was 3.51/100 000 in females, and incidence rate ratio of males and females is approximately 3.25–1.^[3],[4],[5] Especially in the past decade, with the increased incidence of BC, the mortality rate is also gradually increased, which has an extremely threat to human health. Therefore, the early diagnosis and accurate evaluation of stage and muscle invasion are particularly important for the patients with BC.^[6]

Ultrasonography is a very simple and noninvasive imaging examination, which is defined as a technique using echoes of ultrasound pulses to delineate objects or areas of different densities in the body. Recently, with the development of ultrasonic probe manufacturing technology, it is widely used as auxiliary examination to improve the diagnostic accuracy of human diseases, including magnetic resonance imaging (MRI), as a kind of nonray and noninvasive imaging examination, which is widely used in the diagnosis of various diseases, especially in the urinary system. Diffusion-weighted imaging (DWI), as a kind of functional imaging, was functioned through detecting the molecule diffusion motion of tissue water and quantitative data without contrast agent, which were evaluated by the apparent diffusion coefficient (ADC) value. Recent evidence indicated that MRI could be a potential and effective method for diagnosis of BC.^[7],[8]

In the present study, we aim to assess the value of contrast-enhanced ultrasound (CEUS), MRI, and CEUS + MRI in the diagnosis of BC, which could provide a novel strategy for the diagnosis of BC.

> Materials and Methods

Clinical data

Fifty-nine patients were enrolled from September 2012 to December 2015 in this study, including 41 males and 18 females, the maximum age was 88 years old, the youngest was 36 years old, and the average age was 68.83 + 11.89 years. All patients with BC underwent surgical treatment, were diagnosed in pathology, and underwent CEUS and MRI + DWI examinations before surgery. This study was approved by the Ethics Committee of the Tenth People's Hospital of Shanghai (Shanghai, People's Republic of China) (reference number: SHSY-IEC-4.1/19-120/01). All examinations were performed after obtaining written informed consent from patients.

Inclusion criteria

Patients are the first treatment and all patients underwent surgical treatment
The clinical data information (pathological examination, tumor stage, muscle invasion, and expression of p63 gene) is true and complete, clear image imaging
Patients not allergy to contrast agent
No proof of other primary tumors.

Exclusion criteria

Patients unable or did not carry out CEUS and MRI + DWI examination
The abnormal cardiac, pulmonary function and the risk of the presence of critically ill patients
Primary tumors in other parts of the body
Patients with pathologically proven not urinary tract epithelial cancer.

Contrast-enhanced ultrasound image analysis

Physicians with more than 5-year ultrasound examination and diagnostic experience were invited to analyze the data of CEUS. Through image analysis software, the grayscale ultrasound image was observed, compared with the CEUS image, and then conducted a staging diagnosis of BC through observing the tumor enhancement degree, enhanced begin time, enhanced fade time, and the overall tumor enhancement [Figure 1].

Figure 1: Contrast-enhanced ultrasound examination. (a) Synchronous enhancement of bladder wall and tumor (muscle invasive); (b) No enhancement of bladder wall muscle layer (nonmuscle invasive)

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Magnetic resonance imaging + diffusion-weighted imaging image analysis

Physicians with more than 5-year ultrasound examination and diagnostic experience were invited to analyze the data of MRI + DWI. Through image analysis software, the synthetic T1-, T2-weighted imaging and DWI image were observed for the tumor stage diagnosis of BC through analyzing the tumor tissue signal and the surrounding signal. After the workstation to process the original image, ADC value was quantitated by comparing with DWI image with T1-, T2-weighted imaging. In belief, the region of interest (ROI), selected in the bladder wall muscle layer of adjacent tumor tissues, was measured. Each region was measured three times and ADC values were averaged [Figure 2].

Figure 2: Magnetic resonance imaging + diffusion-weighted imaging examination. (a) The continuity of the muscle layer of the bladder wall is complete (nonmuscle invasive); (b) Bladder wall and surrounding tissues are violated (muscle invasive)

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Bladder cancer staging standards

Pathological diagnosis of BC stage and the standard of muscle invasion by UICC released in 2016 the 8^th Edition TNM staging method:^[9] Tis, Ta, T1 BC were defined as for nonmuscle-invasive BC, and T2 and above were defined as muscle-invasive BC.

CEUS judgment BC T staging standard was according to the standards proposed by Caruso for staging.^[10] Ta: bladder mucosa layer and muscle layer were not obviously enhanced; T1: bladder mucosa layer visible and tumor while strengthening, and no bladder wall muscle layer to enhance; T2: bladder mucosa layer and muscle layer were with the tumor while strengthening, bladder tissues showed no enhancement; T3: sync to strengthen the bladder wall full thickness, surrounding tissue and tumor; and T4: in addition to the bladder wall and the surrounding structures of the urinary bladder and other tissues and the surrounding organs visible and tumor synchronous enhancement.

MRI + DWI diagnosis of bladder tumor T staging criteria was according to Sasaki proposed standard for staging.^[11] Ta: bladder wall muscle layer clear, good continuity; T1: tumor in the visible region of small high signal area, or in the high signal area visible within the submucosa exist low signal area, the bladder muscle layer visible low signal continuous area; T2: tumor edge showed high-intensity zone, in the wall of urinary bladder submucosa without low signal area, visible muscle of the bladder wall layer in low signal continuity is destroyed; T3: perivesical tissue visible irregular high signal area invasion; and T4: bladder around other organs in visible area of high signal invasion.

Statistical analysis

Statistical analysis of all the data was carried out by software (version 22; SPSS , Inc ., Chicago , IL, USA). The measurement data were expressed with mean ± standard deviation. Diagnosis accuracy was equal to the number of correctly diagnosed cases divided by the total number. Chi-square test was used to analyze the difference of diagnostic accuracy between the different staging standards. The receiver operating characteristic (ROC) curve was calculated and analyzed for distinguishing bladder wall muscle invasion of ADC threshold. P < 0.05 was considered statistically significant.

> Results

General information

Fifty-nine cases of BC patients were enrolled in this study, including 41 cases of male (69.5%) and 18 cases of female (30.5%), mean age 68.83 + 11.89 years; all patients were found BC in CEUS and MRI + DWI examination. All patients underwent transurethral resection of bladder tumor or radical cystectomy for pathological diagnosis, and pathological specimens were examined by the Pathology Department of the Tenth People's Hospital of Shanghai. The diagnostic results were as follows: 2 cases of Ta stage, 24 cases of T1 stage, 12 cases of T2 stage, 14 cases of T3 stage, and the remaining 6 cases of T4 stage. Pathological diagnosis results were completed by pathology physicians with more than 5 years of work experience [Table 1].

Table 1: General information of patients enrolled in this study

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Results of contrast-enhanced ultrasound and magnetic resonance imaging + diffusion-weighted imaging in the diagnosis of bladder cancer T staging

In this study, pathological diagnosis was considered the gold standard. For CEUS examination, the results showed that 44 of 59 cases with BC had a correct diagnosis in T staging and 11 cases underestimated and 4 cases overestimated the T stage. The total diagnostic accuracy was 74.6% (44/59). For MRI + DWI examination, 45 of 59 cases with BC had a correct diagnosis in T staging and 9 cases underestimated and 5 cases overestimated the T stage. The total diagnostic accuracy was 76.3% (45/59). For the combined diagnosis of two methods, when the higher staging (high) of two methods was taken, a total of 54 cases were diagnosed correctly and 5 cases were wrong, and the total accuracy was 91.5% (54/59). Taking the lower staging (low), a total of 41 cases were diagnosed correctly and 18 cases were wrong, and the total accuracy of diagnosis was 69.5% (41/59) [Table 2]. The diagnostic accuracies of CEUS, MRI + DWI examination, and combined diagnosis (low) had no significant statistical difference (all P > 0.05). The diagnostic accuracy of combined diagnosis (high) was significantly higher than that of CEUS and MRI + DWI, respectively (all P < 0.05) [Figure 3].

Figure 3: Four diagnostic methods for T staging of bladder cancer

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Table 2: Accuracy of diagnosis by different methods

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Contrast-enhanced ultrasound and magnetic resonance imaging + diffusion-weighted imaging examination on the diagnosis of bladder cancer in the case of muscle invasion

In this study, 26/59 cases were diagnosed as nonmuscle-invasive BC (≤ T1), and 33/59 cases were diagnosed as muscle-invasive patients (more than or equal to T2) in pathological diagnosis. For CEUS, in the patients with nonmuscle-invasive BC, 22 cases were diagnosed correctly and 4 cases were misdiagnosed and 26 cases were diagnosed accurately in patients with muscle invasion while 7 cases were misdiagnosed [Table 3]. The diagnostic sensitivity and specificity of CEUS were 86.7% and 75.9%, respectively, and the accuracy was 81.4% (48/59). For MRI + DWI, in patients with nonmuscle-invasive BC, 21 cases were diagnosed correctly and 5 cases were misdiagnosed and 28 cases were diagnosed accurately in patients with muscle invasion while 5 cases were misdiagnosed [Table 4]. The diagnostic sensitivity and specificity of MRI + DWI were 84.8% and 80.8%, respectively, and the accuracy was 83.1% (49/59). There was no significant difference between the diagnostic sensitivity, specificity, and accuracy of two methods (all P > 0.05).

Table 3: Results of contrast-enhanced ultrasound diagnosis of muscle-invasive bladder cancer cases

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Table 4: Results of magnetic resonance imaging + diffusion-weighted imaging diagnosis of muscle-invasive bladder cancer cases

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Combined diagnosis of contrast-enhanced ultrasound and magnetic resonance imaging + diffusion-weighted imaging examination in diagnosis of bladder cancer in the case of muscle invasion

For the combined diagnosis of CEUS and MRI + DWI, when the diagnosis of muscle invasion was defined as one or both of two methods supported muscle invasion (parallel combined diagnosis), 21 cases were accurately diagnosed and 5 cases were misdiagnosed in nonmuscle-invasive patients; in the patients with muscle invasion, a total of 33 cases were accurately diagnosed and no case was misdiagnosed [Table 5]. Thus, the diagnostic sensitivity and specificity of combined in parallel were 86.8% and 100%, respectively, and the accuracy was 91.5% (54/59). When the diagnosis of muscle invasion was defined as both of two methods supported muscle invasion (series combined diagnosis), 23 cases were accurately diagnosed and 3 cases were misdiagnosed in nonmuscle-invasive patients; in the patients with muscle invasion, 24 cases were accurately diagnosed and 9 cases were misdiagnosed [Table 6]. Therefore, the diagnostic sensitivity and specificity of combined in series were 88.9% and 71.9%, respectively, and the accuracy was 79.7% (47/59).

Table 5: Diagnostic results of contrast-enhanced ultrasound and magnetic resonance imaging + diffusion-weighted imaging in parallel with the diagnosis of muscle invasion

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Table 6: Diagnostic results of contrast-enhanced ultrasound and magnetic resonance imaging + diffusion-weighted imaging in series with the diagnosis of muscle invasion

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The accuracy of combined diagnosis CEUS and MRI + DWI (parallel) was 91.5% (54/59), which was obviously higher than that of CEUS and MRI + DWI examination (all P < 0.05), and the accuracy of combined diagnosis CEUS and MRI + DWI (series) was 79.7% (47/59). The diagnostic accuracies of CEUS, MRI + DWI alone, and CEUS and MRI + DWI combined in series had no statistical difference (all P > 0.05) [Figure 4].

Figure 4: Results of four kinds of diagnostic methods for muscle invasion of bladder cancer

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Magnetic resonance imaging + diffusion-weighted imaging value of apparent diffusion coefficient value on the diagnosis of bladder cancer

Combined with postoperative pathological diagnosis results, ADC value was obtained by ROI method. Our results indicated that the average ADC value of bladder wall muscle layer in nonmuscle-invasive BC was 2.01 + 0.26 × 10⁻³ mm L/s, and the average ADC value in muscle-invasive BC was 1.35 + 0.33 × 10⁻³ mm L/s, and the ADC value of two groups has a significant difference (P < 0.01) [Figure 5]. ROC curve was drawled to assess the diagnostic value of ADC in BC. Our data showed that the area under curve was 0.959, the diagnostic sensitivity and specificity were 92.3% and 81.8%, respectively, and the diagnostic accuracy was 84.7% (50/59) with a diagnostic threshold of 1.65 × 10⁻³ mm L/s [Figure 6]. The diagnostic sensitivity, specificity, and accuracy were not significantly different compared with those of CEUS and MRI + DWI alone (all P > 0.05).

Figure 5: Distribution of apparent diffusion coefficient value distribution in muscle-invasive bladder cancer and nonmuscle-invasive bladder cancer

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Figure 6: Apparent diffusion coefficient value of receiver operating characteristic in the diagnosis of muscle invasion in bladder cancer

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> Discussion

At present, the common diagnostic methods for BC are imaging examination, tumor marker detection, biopsy of the bladder, and diagnosis of electrical resection. Moreover, definition of T staging and muscle invasion was crucial for the diagnosis of BC. In this study, we found that combined diagnosis of CEUS and MRI + DWI was a noninvasive and accurate method for the patient with BC.

Ultrasonography is the first choice for the diagnosis of BC, which may be detected through the abdomen, rectum, and transurethral. A recent study demonstrated that ultrasonography had more diagnostic advantage than other imaging examinations for low stage of BC. Tadin et al.^[12] reported that the diagnostic accuracy of ultrasonography could be to up 90% for T1 stage of bladder cancer, but only up to 84 % for the T 2 stage. CEUS, as an auxiliary examination, is widely used for the diagnosis of human diseases, which could enhance contrast through injecting contrast agent and clearly displaying the blood supply of the tumor region and surrounding tissues. Emerging evidence showed that CEUS had more advantage in the diagnosis of T staging of BC, compared to conventional ultrasound examination.^[13],[14] Consistently, in our study, the diagnostic accuracy of CEUS for T staging of BC was 74.6%, in which diagnostic accuracy for T1 and Ta was 84.6% and for higher stages was 66.7%. In addition, 11 cases were underestimated the pathological staging and 4 patients were overestimated the pathological stage. The underlying reasons for underestimating the T stage were as follows: (1) hierarchical boundaries of muscle layer of bladder wall were not clear in ultrasound images and (2) ultrasound could be easily affected by subjective condition of patients, which may lead to misjudge the echo of the bladder wall muscle layer and surrounding structures of the urinary bladder. The underlying reasons for overestimating the T stage were as follows: (1) the bladder was excessively felt and (2) the bladder wall is thin, which could result in echo enhancement.^[15],[16] Moreover, a recent study indicated that CEUS could be a diagnostic method for muscle invasion of BC.^{[17],[18],[19],[20]} In the present study, the overall accuracy of CEUS for muscle invasion was 81.4%, the sensitivity was 86.7% and the specificity was 75.9%. These results were approximately consistent with the previous studies.

MRI was extensively used for the detection of BC, which could make a more detailed evaluation for primary tumors and tumor surrounding invasion degree by differences contrast between T1-weighted imaging and T2-weighted imaging. DWI could display more clear features of the tumor tissue through observing the diffusion of water molecules.^[21] In the past decades, many studies had shown that MRI + DWI had more significant advantages in the diagnosis of T staging of BC, compared to that with computed tomography, which had an accuracy of 68%–92%.^{[22],[23],[24],[25]} In addition, it has been reported that MRI + DWI was more accurate in the diagnosis of tumor surrounding tissues and lymph nodes, and had the same high accuracy as enhanced MRI in the diagnosis of T staging of BC.^[22],[26] Therefore, MRI + DWI had a better application value in the diagnosis of BC due to its higher accuracy, no radiation, and no contrast agent. In this study, the total accuracy of MRI + DWI for the diagnosis of BC T staging was 76.3%, which was higher than that of CEUS, but the difference had no statistically significance. Similar to the data of CEUS, 9 cases were underestimated the pathological staging and 4 patients were overestimated. One reason for underestimating the T-stage could be that MRI + DWI are tomography methods, which could miss smaller metastasis and invasion.Using MRI + DWI in patients with nonmuscle -invasive bladder cancer, the diagnostic sensitivity was 84. 8%, the specificity was 80.8%, and the accuracy was 83.1%. The accuracy of the combined CEUS and MRI + DWI (parallel) was significantly higher than that of CEUS or MRI + DWI alone.

> Conclusion

We found that the accuracy of CEUS and MRI + DWI combined diagnosis was higher than that with the single diagnostic method. CEUS and MRI + DWI combined diagnosis was a feasible and effective method for the clinical diagnosis of BC.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the Tenth People's Hospital of Shanghai, and all participants provided written informed consent before registration. The study is also in line with the Helsinki Declaration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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