|Year : 2014 | Volume
| Issue : 4 | Page : 878-882
The usefulness of diffusion-weighted magnetic resonance imaging in bladder cancer staging and functional analysis
Yasushi Yamada1, Shigeki Kobayashi2, Shiho Isoshima2, Kiminobu Arima1, Hajime Sakuma2, Yoshiki Sugimura1
1 Department of Urology, Mie University School of Medicine, Tsu, Mie Prefecture, Japan
2 Department of Radiology, Mie University School of Medicine, Tsu, Mie Prefecture, Japan
|Date of Web Publication||9-Jan-2015|
Edobashi 2-174, Tsu - 514 8507
Source of Support: None, Conflict of Interest: None
Aim: We assessed the effect of adding diffusion-weighted magnetic resonance imaging (DW-MRI) to conventional MRI for T staging and the correlation between apparent diffusion coefficient (ADC) values and clinicopathological parameters for patients with bladder cancer.
Materials and Methods: We retrospectively reviewed the records of 160 patients with bladder cancer who underwent MRI at our institute. All patients were routinely assessed with conventional MR imaging. Since January 2008, we added DW-MRI.
Results: In these 160 patients, 127 (79.4%) tumors were detectable by MRI. In all patients with detectable tumors, on a stage-by-stage basis, 96 (75.6%) of 127 patients received the correct diagnosis. With DW-MRI, accurate diagnosis was obtained in 80 (80.0%) of 100 cases; without DWI in only 16 (59.3%) of 27 cases (P = 0.026). For T staging, the accuracy for distinguishing muscle invasion (T ≦_ 1 vs T ≧_ 2) with DW-MRI (83.0%) was superior to that without DW-MRI (66.7%). The accuracy for distinguishing perivesical fat invasion (T ≦_2 vs T ≧_3) with DW-MRI (98.0%) was also superior to that without DW-MRI (92.6%). The ADC values were significantly related with tumor diameter (<3 cm vs ≧_ 3 cm,P < 0.001), histopathological grade (low grade vs high grade, P < 0.001), T stage (≦_T1 vs ≧_T2,P < 0.001), and operative method (transurethral resection vs total cystectomy, P < 0.001).
Conclusions: We demonstrated that DW-MRI is not only useful for bladder cancer T staging, but also a prognostic factor for patients with bladder cancer.
摘要 目的：我们评估了磁共振扩散加权成像（DW MRI）相比传统磁共振对对膀胱癌患者T分期的影响，以及表观扩散系数和临床病理参数值之间的相关性。
结果：在这160例患者中，127（79.4%）例肿瘤由MRI检测出。在所有可检测到肿瘤的患者中，基于逐步检查的原则，127例中96例（75.6%）患者接受正确的诊断。DW MRI中，80（80%）/100例得到准确的诊断；无DWI仅16（59.3%）/27例（P = 0.026）。T分期的准确性，区分肌肉浸润(T ≤_ 1 vs T ≥_ 2)DW MRI（83%）明显优于无DW MRI（66.7%）。膀胱周围脂肪浸润的识别精度(T ≤_2 vs T ≥_3) DW MRI（98%）也优于无DW MRI（92.6%）。ADC值与以下参数显著相关：肿瘤大小 (<3 cm vs ≥_ 3 cm, P < 0.001)，组织学分级（低级别与高级别，P＜0.001），T分期(≤_T1 vs ≥_T2, P < 0.001)，手术方法（经尿道切除和膀胱全切除术，P＜0.001）。
Keywords: Apparent diffusion coefficient, bladder cancer, diffusion-weighted, magnetic resonance imaging
|How to cite this article:|
Yamada Y, Kobayashi S, Isoshima S, Arima K, Sakuma H, Sugimura Y. The usefulness of diffusion-weighted magnetic resonance imaging in bladder cancer staging and functional analysis. J Can Res Ther 2014;10:878-82
|How to cite this URL:|
Yamada Y, Kobayashi S, Isoshima S, Arima K, Sakuma H, Sugimura Y. The usefulness of diffusion-weighted magnetic resonance imaging in bladder cancer staging and functional analysis. J Can Res Ther [serial online] 2014 [cited 2019 Nov 18];10:878-82. Available from: http://www.cancerjournal.net/text.asp?2014/10/4/878/138225
| > Introduction|| |
Bladder cancer is one of the most common urological malignancies. Non-muscle invasive bladder cancer is treated with transurethral resection (TUR), whereas muscle-invasive bladder cancer is treated with total cystectomy, palliative chemotherapy, or radiation therapy. As such, primary judgment by clinical T staging affects the selection of treatment method. Clinicopathological findings, such as histopathological grading or T staging, also provide information for the selection of treatment method. However, these parameters are rough qualitative methods. To give more accurate information and to tailor treatment to the needs of each individual patient, a quantitative marker that reflects the aggressiveness of the tumor is needed.
Magnetic resonance imaging (MRI) has an important role in bladder cancer assessment. It was reported that dynamic contrast-enhanced MRI (DCE-MRI) is superior to computed tomography (CT) in detecting bladder cancer;  however, it was also indicated that staging errors exist to some degree.  Therefore, it is expected that new imaging modality will be developed to provide more accurate assessments.
Diffusion-weighted MRI (DW-MRI) reflects changes in water mobility at the cellular or physiologic level. This technique provides tissue contrast more clearly than conventional T1-MRI and T2-MRI. DW-MRI is useful for the detection of tumor tissues, in which water mobility is restricted. Recently, the value of DW-MRI for several types of cancer has been reported.  Several reports also demonstrated the usefulness of DW-MRI for identifying the T stage of bladder cancer. ,,, In addition to diagnostic advantage, it was also shown that the apparent diffusion coefficient (ADC) was associated with clinical and pathological parameters. ,,,
Prior to January 2008, we evaluated patients with bladder cancer through T2-MRI and DCE-MRI. Since January 2008, we added DW-MRI to our protocol. In the current analysis, we estimated the additional information provided by DW-MRI for T staging of patients with bladder cancer and with regard to the association between the ADC and clinicopathological features.
| > Materials and methods|| |
From February, 2006 to January, 2013, 160 patients underwent bladder MRI at our institute. Since January 2008, we added DW-MRI to our protocol for the assessment of bladder cancer patients. All patients included in our study were diagnosed with urothelial carcinoma by biopsy, and pathological staging were confirmed by surgical resection. The cystoscopic characteristics, such as the number or diameter of tumors, were recorded. An institutional review board approved this study.
All patients were restricted from urination for 1 hour before MRI, and drinking water was promoted. MRI was performed with a 1.5-Tesla system (SIGNA Excite HDxt 1.5T; GE, Milwaukee, USA) with a maximum gradient amplitude of 40 mT/m and a slew rate of 150 T/m/sec. An eight-channel cardiac array coil was used in all MR sequences. Axial spin-echo T1-weighted imaging was performed with the following parameters: Repetition time, 434-550 ms; echo time, 13 ms; matrix, 256 Χ 256; field of view, 22 cm; slice thickness, 5 mm; interslice gap, 2 mm; number of slices, 15-19; number of excitations, 1.5; bandwidth, 19.23 kHz. Axial, sagittal, and coronal fast spin-echo T2-weigted MRI were performed with the following parameters: Repetition time, 3,000 ms; echo time, 85 ms; matrix, 320 Χ 320; field of view, 22 cm; slice thickness, 5 mm; interslice gap, 2 mm; number of slices, 15-19; number of excitation, 2; bandwidth, 15.23kHz [Figure 1]a. Axial DW-MRI with single-shot echo planar MRI was performed with the following parameters: Repetition time, 5,000-6,000 ms; echo time, 68.7 ms; matrix, 128 Χ 128; field of view, 40 cm; slice thickness, 5 mm; interslice gap, 2 mm; number of slices, 15-19; number of excitations, 6; bandwidth, 250 kHz; 2 different diffusion gradient b-values, b = 0 and 1,000 s/mm  [Figure 1]b. The ADC map was constructed for all cases on a voxel-by-voxel basis using a b-value of 1,000 s/mm.  Contrast-enhanced imaging was performed with axial, sagittal, coronal gradient echo T1-weighted MRI after administration of gadopentetate dimeglumine (Magnevist; Bayer Yakuhin, Osaka, Japan), with a dose of 0.2 ml/kg body weight as a bolus injection with the following parameters: Repetition time, 120 ms; echo time, 2.2 ms; matrix, 256 Χ 160; field of view, 26 cm; slice thickness, 5 mm; interslice gap, 2 mm; number of slices, 12; number of excitations, 1; bandwidth, 31.25 kHz.
|Figure 1: MR imaging of a 75-year-old man with bladder cancer (cT3a). (a) 2-weighted imaging shows a low-intensity bladder tumor (white arrow). The border between the tumor and the normal tissue is unclear. (b) Diffusion-weighted imaging represents the tumor (white arrow) clearly, and easily distinguishes the muscle layer. (c) On the ADC map, the measurement of the ADC value of the tumor (black arrow) is made by circling the region of interest (ROI, white circle)|
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All images were analyzed using the func tool software (General Electric Medical System, Milwaukee, WI, USA) and were prospectively interpreted by a single radiologist (S.K.). We assessed main tumor per one patient in the patients with multiple tumor. The ADC measurements were conducted through a circular region of interest (ROI) on a tumor region [Figure 1]c. Clinical T stage was classified as ≤_T1, T2, T3, and T4 according to the 2002 TNM system,  and was applied by using radiologic criteria similar to those previously described. , Pathological diagnosis was performed by transurethral resection (TUR) or total cystectomy. The cases diagnosed pathologically as T1 by the initial TUR were confirmed at the final stage by a second TUR.
Tumor detection rates were analyzed according to tumor diameter (e.g., 5 mm, 10 mm). The accuracy of the tumor staging diagnosis was estimated on a stage-by-stage basis. Comparisons of the diagnostic accuracy between evaluations with DW-MRI and without DW-MRI were performed with a chi square test. Associations between mean ADC values and clinicopathological parameters, such as number of tumors, tumor diameter, histopathological grade, pT stage, and operative method, were analyzed with an unpaired t-test. Statistical analyses were performed using SPSS for Windows, version 18.0 (SPSS, Chicago, USA).
| > Results|| |
We analyzed a total of 160 patients. Their clinical and pathological characteristics are listed in [Table 1] and [Table 2], respectively. MRI was performed with DW-MRI in 123 cases and without DW-MRI in 37 cases. DCE was routinely used, in a total of 144 cases. In these 160 patients, 127 (79.4%) bladder tumors were detectable by MRI. The distribution of tumor diameter for detectable and undetectable tumors is shown in [Figure 2]. For undetectable tumors, the largest tumor was 9 mm in diameter. Detection rates according to tumor diameter are listed in [Table 3]. For tumors <5 mm in diameter, 3 (11.1%) of 27 cases were detectable, and for tumors 5-10 mm in diameter, 17 (35.4%) of 26 cases were detectable, and for tumors >10 mm in diameter, 107 (100%) of 107 cases were detectable. In all tumors <10 mm in diameter, pathological stages were pT1 or lower. No significant differences were observed in detection rates between analysis with DW-MRI and without DW-MRI (data not shown).
|Figure 2: Tumor diameter of detectable and undetectable bladder cancer by MRI. The diameter of undetectable tumors increases to the left. The largest diameter of undetectable tumors was 9 mm. The sensitivity of bladder tumor detection was 94.7% at ≦5 mm, and 100% at ≧10 mm|
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Of all cases in which a tumor was detectable (n = 127 patients), on a stage-by-stage basis, 96 (75.6%) were correctly staged, 25 (19.6%) were overstaged, and 6 (4.7%) were understaged. Stage-by-stage results with or without DW-MRI are shown in [Table 4]. Tumors were significantly more frequently correctly staged with DW-MRI (80 [80.0%] of 100 cases than without DW-MRI (16 [59.3%] of 27 cases; (P = 0.026). Mis-staging with DW-MRI was observed for 15 (15.0%) cases that were overstaged and 5 (5.0%) cases that were understaged.
|Table 4: Staging results with DWI and without DWI on a stage-by-stage basis|
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The accuracy of T staging diagnosis for distinguishing muscle invasion (T ≤_1 vs T ≥_2) with DW-MRI (83.0%) was superior to that without DW-MRI (66.7%) [Table 5]. The accuracy for distinguishing perivesical fat invasion (T ≤_2 vs T ≥_3) with DW-MRI (98.0%) was also superior to that without DW-MRI (92.6%) [Table 6]. The ADC values of detectable tumors were measured in 99 patients. The associations between ADC values and clinicopathological parameters are summarized in [Table 7]. The ADC values were significantly related with tumor diameter (3 cm vs ≥_3 cm, P < 0.001), histopathological grade (low grade vs high grade, P < 0.001), pT stage (≥_T1 vs ≥_T2, P < 0.001), and operative method (TUR-BT vs total cystectomy, P < 0.001).
|Table 5: Diagnostic accuracy for differentiating muscle invasive from non-muscle invasive bladder cancer (≦T1 vs ≧T2)|
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|Table 6: Diagnostic accuracy for differentiating organ-confined from non-organ-confined tumors (≦T1 vs ≧T2)|
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|Table 7: Association between ADC values and clinicopatholigical parameters|
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T staging of bladder cancer has an important role in the appropriate choice of therapy. Although MRI is superior to CT, its accuracy in T staging is limited.  Even now, TUR is recommended for the staging of bladder cancer. Recently, for more accurate staging of bladder cancer, a second TUR is recommended. The significance of the second TUR is early detection of muscle-invasive bladder cancer. If a new useful modality is developed, it is expected that these TURs may be unnecessary.
DW-MRI is a convenient and safe technique that does not require a long examination time or a contrast agent, which may cause adverse effects, including nephrogenic systemic fibrosis.  DW-MRI is used in several urological malignancies, such as prostate cancer, upper urinary tract cancer, and kidney cancer. , In bladder cancer, several studies have shown that the accuracy of T staging with DW-MRI exceeds that of conventional methods. ,,, We also showed that DW-MRI provides significant additional information for the T staging of bladder cancer. We think that the reason it achieves more accurate staging is that it enables the shapes of the tumor to be more clearly distinguished. Thus, we expect that this technique will be used instead of DCE-MRI. This substitution can reduce the incidence of adverse events related to the use of contrast agents, and shorten the examination time, while maintaining a high diagnostic level.
In the current study, we demonstrated that the addition of DW-MRI improves T staging in bladder cancer. For small tumors, MRI including DW-MRI is limited in tumor detection. We showed that the tumor detection rate was 14.7% for tumors ≤_5 mm in diameter and 37.7% for tumors ≤_10 mm in diameter. Because these undetectable tumors were all pT1 or under, it is suspected that the risk of muscle invasion is very low with small tumors. Thus, we propose that these small tumors do not need T staging with MRI, which sometimes increases cost, time, and the risk of adverse events. However, 94.7% of the tumors ≥_5 mm in diameter could be detected. Moreover, all of the tumors ≥_10 mm in diameter could be detected. These results suggest the possibility of screening for significant bladder cancer with whole-body MRI.  Although we showed an additional effect of DW-MRI, overstaging was relatively high in our study. With DW-MRI, 15 (60.0%) of 25 cases that were clinically T2 were pathologically T1. It is difficult to determine with certainty whether muscle invasion of the tumor exists with DW-MRI. Therefore, even if a tumor is diagnosed clinically as T2, staging TUR may be needed. On the other hand, for the tumors that were diagnosed clinically as T3 or more, understaging was not found.
We also showed a significant association between the ADC values and clinicopathological parameters, such as tumor diameter, histopathological grade, T stage, and operative method. It has been clearly proven that these parameters predict recurrence and progression risk.  Thus, it is expected that the ADC values related to these parameters may be prognostic factors. Because the advantage of the ADC value is not just qualitative but also quantitative, this marker may enable patient-specific therapy for each patient. Another quantitative tool for the estimation of cancer behavior is Positron Emission Computed Tomography (PET-CT). However, this modality is often difficult for assessment of urological cancer because of artifacts from urinary excretion. Yoshida et al.  reported that the measurement of ADC values predicted therapeutic response of chemoradiotherapy against muscle-invasive bladder cancer. Recently, Kobayashi et al.  revealed a significant inverse correlation between ADC values and Ki-67 labeling index in bladder cancer. These results support the viewpoint that ADC values reflect the aggressiveness of bladder cancer. In the future, it is expected that the ADC values of tumors may be helpful in making treatment decisions for patients with bladder cancer.
Our study has several limitations. Because it is retrospective and not a case-control study, the number of patients and the distribution of clinicopathological parameters between assessments with DW-MRI and without DW-MRI were not divided equally. In particular, the number of cases detected without DW-MRI was 27, while the number of cases detected with DW-MRI was 100. However, the diagnostic performance of DW-MRI itself in our study was in line with that of other reports. ,,, Another limitation was that we assessed the results using the total sequence, which combined T2-MRI, DCE-MRI, and DW-MRI. So, we did not assess the sensitivity of DW-MRI alone. To solve the above limitations, we suggested that a prospective, case-control study that compares the accuracy of DCE-MRI and DW-MRI in T staging of bladder cancer is warranted. In conclusion, the addition of DW-MRI to conventional MRI may not only improve the accuracy of T staging of bladder cancer, but also may aid in the prognosis of bladder cancer. We recommend the routine use of DW-MRI for the evaluation of patients with bladder cancer.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]