1413.pdf 866 | Urological Oncology 1Department of Radiology, Hazrat Rasoul Akram University Hospital; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2Research Unit, Medical Imag- ing Center, Tehran University of Medical Sciences, Tehran, Iran 3School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4Department of Urology, Hazrat Rasoul Akram University Hospi- tal, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 5Deputy of Research and Tech- nology, Ministry of Health and Medical Education, Tehran, Iran Mahyar Ghafoori,1 Madjid Shakiba,2 Atefeh Ghiasi,3 Nazanin Asvadi,3 Kamal Hosseini,5 Manijeh Alavi6 Value of MRI in Local Staging of Bladder Cancer Corresponding Author: Mahyar Ghafoori, MD Department of Radiology, Hazrat Rasoul Akram University Hospital, Niyayesh St., Shahrara, Tehran, 1445613131, Iran Tel: +98 21 6650 9057 Fax: +98 21 6651 7118 E-mail: mahyarghafoori@gmail. com Received March 2012 Accepted August 2012 Purpose: To evaluate the accuracy of magnetic resonance imaging (MRI) in bladder cancer Materials and Methods: A total number of 108 bladder tumors in 86 patients (86% men and 14% women) were evaluated by 1.5 Tesla MRI machine. The tumor stages that were deter- mined by MRI study were compared with pathology results after resection of the tumor. Results: The most common stage determined by both MRI and pathology was T2a. Consider- P MRI and pathology was 0.87 (P < .0001). Considering stages in details, we had 22 (20.3%) mismatches in staging between MRI and pathology; 10 (45.5%) were underestimation and 12 (54.5%) were overestimation. Combining groups a and b in each stage, we had 14 (13%) mis- match cases; 6 (46.2%) were underestimation and 8 (53.8%) were overestimation. The detec- tion rate of MRI was 0% in stage Ta, 80% in stage T1, 88.1% in stage T2, 81.2% in stage T3, - Conclusion: Magnetic resonance imaging is a reliable modality for determining the stage of bladder tumors with high accuracy, and could show the depth of invasion and extension of tumor that is useful for treatment planning. Keywords: urinary bladder neoplasms, magnetic resonance imaging, neoplasm staging UROLOGICAL ONCOLOGY 867Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L MRI in Local Staging of Bladder Cancer | Ghafoori et al INTRODUCTION Bladder cancer is one of the most common malignan-cies of the urinary tract that accounts for almost 4% of all malignancies.(1) Bladder tumors considering the depth of invasion are categorized into different stages. TNM staging system is the accepted method for worldwide staging of bladder cancer.(2) Histopathologic evaluation of the tumor after surgical resection or transurethral resection - nent of tumor stage. Since tumor staging is crucial for choosing the treatment method, a reliable modality for pretreatment staging is nec- essary. Magnetic resonance imaging (MRI) has been recog- nized as the best imaging modality for bladder cancer stag- ing.(3,4) Since there has been no published study about the accuracy of MRI in bladder cancer staging in Iran, we con- ducted this study to evaluate the accuracy of MRI in deter- tumors from invasive one. MATERIALS AND METHODS Magnetic resonance imaging of the bladder was performed for all the patients who were diagnosed as having bladder masses by means of ultrasonography, computed tomography scan, or MRI, and were referred to the department of radiol- ogy in Hazrat Rasoul Akram University Hospital from De- cember 2009 to April 2011. have bladder cancer by histopathologic study were enrolled in this study. Patients without documented bladder cancer, those who could not perform MRI study because of cardiac pacemakers or metallic objects in their bodies, and patients that refused to undergo MRI because of claustrophobia or any other reasons were excluded from the study. Magnetic resonance imaging of the bladder was performed in all the patients by a 1.5 Tesla MRI machine (Avento; Sie- mens, Erlangen, Germany) using pelvic-phased array coil. Our MRI protocol was as follows: Axial, coronal, and sagit- tal T2-weighted fast spin-echo, axial T1-weighted fast spin- echo, axial fat suppressed T1-weighted fast spin-echo, and axial and coronal 3D volumetric interpolated breath-hold sequence (VIBE) before and after administration of intrave- nous contrast medium. All the images were reviewed by an expert uroradiologist in the workstation. Staging of bladder tumors was performed stages that were determined by MRI were compared with pathologic staging after resection of tumors. In 10 patients with 11 tumors, TUR of the tumor and in 76 patients with 97 tumors, radical cystectomy was performed. In six patients, the procedure was repeated between 3 to 5 weeks after the The following guidelines were used for staging by MRI: An intact hyposignal line (muscle layer) at the base of the - ner margin of the hyposignal line, stage T2a; a disrupted hy- lesion with an irregular, shaggy outer border and streaky ar- eas of the same signal intensity of the tumor in perivesical fat, stage T3b (Figure 2); and a lesion extending into an adjacent organ or abdominal and pelvic side walls with the same sig- nal intensity of the primary tumor, stage T4a or T4b.(3) Since the most important factor in the selection of the curative mo- dality is the depth of tumor invasion, we only considered the T stage of the tumor from the TNM system. - than evaluation of MRI accuracy in each stage, we evalu- two groups:(4) to T1 - Invasive tumors: if the tumor stage was more than or equal to T2a Extension of the tumor beyond the bladder and involvement - mor recurrence and patients’ survival. The accuracy of MRI tumors into two groups:(4) to T2b equal to T3b The Ethics Committee of Tehran University of Medical Sci- ences approved the protocol for the research project. This study conforms to the provisions of the Declaration of Hel- sinki (as revised in Edinburgh 2000). The objectives and methods of the study were explained to all the subjects and a written informed consent was obtained. Statistical Analysis 868 | and pathology. Furthermore, we assessed the diagnostic in- value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the MRI versus pathology as gold standard results. Data were analyzed by SPSS software (the Statistical Package for the Social Sciences, Version 16.0, SPSS Inc, Chicago, Illinois, USA) and P < .05 was assumed RESULTS Overall 108 tumoral lesions were diagnosed histopathologi- cally as transitional cell carcinoma. Seventy-four of the pa- tients were men (86%) and 12 were women (14%). The mean ± standard deviation age of the patients was 59.7 ± 12 years (range, 32 to 86 years). The mean age of the men and women was 61.9 ± 15.6 years and 59.4 ± 12.7 years, respectively (P = .53). Based on MRI, the most common stage was T2 [43 (39.8%) - garding histopathology results, again stage T2 was the most common stage that was diagnosed in the patients (42 tumors; 25 in the T2a and 17 in the T2b stage; Table 1). Regarding tu- mor location, the most common tumor site was the posterior between MRI and histopathology was 0.8 (P < .0001; Ta- ble 2). Combining groups a and b in each stage for MRI and Urological Oncology Table 1. Details of tumor stages based on MRI and histopathology. Ta T1 T2 T3 T4 MRI, n (%) 0 11 (10.2) 43 (39.8) 28 (25.9) 26 (24.1) a b a b a b 0 11 (10.2) 30 (27.8) 13 (12) ----- 28 (25.9) 18 (16.7) 8 (7.4) Histopathology, n (%) 1 (0.9) 10 (9.3) 42 (38.9) 32 (29.6) 23 (21.3) a b a b a b 1 (0.9) 10 (10.2) 25 (23.1) 17 (15.7) 7 (6.5) 25 (23.1) 15 (13.9) 8 (7.4) MRI indicates magnetic resonance imaging. Figure 1b. Coronal T2-weighted image.Figure 1a. Axial T2-weighted image. 869Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L between MRI and pathology (P < .0001; Table 3). Considering detailed stages, we had totally 22 mismatch cas- es. As it is shown in Table 2, 10 (45.5%) of these mismatches were underestimation and 12 (54.5%) were overestimation. Eight cases happened in the same stage, but different subdivi- sions (eg, stage T2a was reported as T2b). Therefore, we had totally 14 (13%) mismatch cases in staging between MRI and pathology. As Table 3 shows, there were totally 8 (53.8%) cases of stage overestimation and 6 (46.2%) cases of stage underestimation. The detection rates of MRI in each stage were as follows: Stage Ta, 0%; stage T1, 80%; stage T2, 88.1%; stage T3, 81.2%; and stage T4, 100%. Considering stages Ta and T1 as - culated the kappa agreement and diagnostic indices of MRI versus pathology as the gold standard. The sensitivity and the kappa agreement and diagnostic indices of MRI versus - ity of MRI were 0.93 and 0.94, respectively (Table 5). DISCUSSION T2a was the most common stage that was diagnosed by both MRI and histopathology in our study that is in contrast with western countries, in which T1 is the most common diag- nosed bladder cancer.(5-7) This could be due to later admis- sion of patients to physicians in Iran. If we consider all stages in details, including a and b sub- groups in each of the T stages, and compare it with pathology results, we had totally 22 (12.2%) cases of mismatch between MRI staging and pathology reports. Of those, 10 (45.5%) were underestimation and 12 (54.5%) were overestimation. Since 8 mismatch cases were seen in the same T stages, then considering the T component of staging alone, regardless of a or b subgroup, the number of over- or under-staging decreas- es to totally 14 (13%) mismatch cases; of which 6 (46.2%) were underestimation and 8 (53.8%) were overestimation re- sulting in more accuracy of MRI in staging. In a study by Tekes and colleagues, most patients (32%) were over-staged (P < .0001),(4) which is similar to our study. Buy Table 2. Agreement of MRI and histopathology considering staging. MRI Staging Total Ta T1 T2 T3 T4 a b a b a b Pathology Staging Ta Ta 0 1 0 0 0 0 0 0 1 T1 T1 0 8 2 0 0 0 0 0 10 T2 a 0 2 22 1 0 0 0 0 25 b 0 0 4 10 0 2 1 0 17 T3 a 0 0 2 2 0 3 0 0 7 b 0 0 0 0 0 23 2 0 25 T4 a 0 0 0 0 0 0 15 0 15 b 0 0 0 0 0 0 0 8 8 Total 0 11 30 13 0 28 18 8 108 MRI indicates magnetic resonance imaging. MRI in Local Staging of Bladder Cancer | Ghafoori et al Figure 1c. Axial fat-suppressed T1-weighted image with contrast. A tumoral mass is evident in the right lateral wall of the bladder that shows enhancement after contrast medium injection. The hyposignal muscular layer under the tumor is intact with no evidence of tumor invasion, a finding that is consistent with stage T1 tumor. 870 | and associates reported 33% underestimation in their study (P < .0001). They assessed their patients with a 0.5T MRI scanner without contrast agent injection. Furthermore, their study had a much smaller sample size compared to ours.(8) Considering all stages in details, including a and b subdivi- sions, the detection rate of MRI was equal to 80% that points to a good correlation between MRI and pathology (Table 2). If we consider T stages alone, regardless of a and b subdivi- sions, the detection rate of MRI becomes even much better and equal to 87% because many over- or under-stagings hap- pened in the same T stage (stage a was diagnosed as stage b or vice versa) (Table 3). Over-staging was more common than under-staging in our study. Abnormal signals that are detected in perivesical fat at the site of the tumor and are misdiagnosed as tumor invasion are one of the reasons for over-staging of bladder cancer. The source of these abnormal signals could be hyperemia and en- gorged vessels in the vicinity of the tumors due to their high process that happens in perivesical tissues following TUR or biopsy of bladder tumors,(1) especially in T2-weighted and gadolinium-enhanced images.(3,9-11) The most common un- der-staging happened between stages T2a and T2b and was due to underestimation of the depth of tumor invasion into the hyposignal muscular layer of the bladder. Among all mismatch cases between MRI and pathology, in more than 90% of misstaged tumors, the over-or under-stag- ings were diagnosed by MRI only as one stage higher or low- er than the histopathology diagnosis. Only in one case, a T2b stage tumor was diagnosed in MRI as T4a tumor, which was a posteriorly located tumor with obliterated fat plan between the tumor and the adjacent seminal vesicle presumably due to vesicle involvement. The overall reported accuracy of MRI in local staging of bladder cancer is between 52% and 93%. (3,4,12,13) The use of gadolinium can increase this accuracy to 73% to 100%.(4) To determine the treatment plan and the patient’s prognosis, - cer is very important. The treatment is dramatically changed Urological Oncology Table 3. Crosstabulation of MRI and pathology results in terms of staging. Pathology Total Ta T1 T2 T3 T4 MRI Ta 0 0 0 0 0 0 T1 1 8 2 0 0 11 T2 0 2 37 4 0 43 T3 0 0 2 26 0 28 T4 0 0 1 2 23 26 Total 1 10 42 32 23 108 MRI indicates magnetic resonance imaging. Figure 2b. Coronal T2-weighted image.Figure 2a. Axial T2-weighted image. 871Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L are treated with TUR with or without adjuvant intravesical chemotherapeutic agents while deep tumors are treated by more aggressive approaches, including cystectomy and pal- liative chemotherapy, radiotherapy, or both.(14) - mors, the reported accuracy is 75% to 92%.(4,15,16) Accord- ing to our study, the kappa agreement between MRI and his- and 0.82, respectively. Using 1.5 Tesla MRI machine with T1-weighted and T2-weighted images, Tekes and colleagues - by reviewer 2.(4) Takeuchi and coworkers used T2-weighted images alone, T2-weighted with diffusion weighted (DW) images, T2-weighted plus contrast agent images, and all three together with a 1.5 Tesla MRI machine. They reported enhanced images were 94% and 86%, respectively, and of T2-weighted plus DW images were 88% and 100%, respec- tively.(7) Magnetic resonance imaging has been shown highly accu- rate in diagnosing perivesical fat involvement considering previous studies.(17) Our study showed that the sensitivity which is a satisfying result. Abou-El-Ghar and colleagues evaluated the accuracy of MRI in staging of bladder carcino- mas and compared two MRI techniques with a 1.5 Tesla MRI in DW images and 75.7% in T2-weighted images. The accu- - (69.7% versus 15.1%; P < .001).(18) Takeuchi and associates found that in T2-weighted contrast enhanced images, MRI Table 4. Diagnostic indices of MRI versus pathology in differentiation of superficial and deep tumors. Diagnostic Index Sensitivity (95% CI) 0.98 (0.93 to 0.99) Specificity (95% CI) 0.82 (0.48 to 0.98) Positive predictive value (95% CI) 0.98 (0.93 to 0.99) Negative predictive value (95% CI) 0.82 (0.48 to 0.98) Positive likelihood ratio (95% CI) 5.4 (1.5 to 18.9) Negative likelihood ratio (95% CI) 39.7 (99.8 to 160.8) Kappa agreement (95% CI) 0.8 (0.61 to 0.99) MRI indicates magnetic resonance imaging; and CI, confidence interval. Table 5. Diagnostic indices of MRI versus pathology in differentiation of organ-confined and non-organ-confined tumors. Diagnostic Index Sensitivity (95% CI) 0.93 (0.82 to 0.98) Specificity (95% CI) 0.94 (0.84 to 0.99) Positive predictive value (95% CI) 0.94 (0.85 to 0.99) Negative predictive value (95% CI) 0.93 (0.82 to 0.98) Positive likelihood ratio (95% CI) 16.4 (5.4 to 49.3) Negative likelihood ratio (95% CI) 12.9 (5 to 33.4) Kappa agreement (95% CI) 0.87 (0.78 to 0.96) MRI indicates magnetic resonance imaging; and CI, confidence interval. MRI in Local Staging of Bladder Cancer | Ghafoori et al Figure 2d. Coronal fat-suppressed T1-weighted image with con- trast. A tumoral mass is evident in the left lateral wall of the blad- der that shows enhancement after contrast medium injection. The full thickness of the bladder wall is involved by the tumor and invasion of the tumor to perivesical fat is noted, a finding that is consistent with stage T3b tumor.Figure 2c. Axial fat-suppressed T1-weighted image with contrast. 872 | Urological Oncology 8. Buy JN, Moss AA, Guinet C, et al. MR staging of bladder carcinoma: correlation with pathologic findings. Radiology. 1988;169:695-700. 9. Neuerburg JM, Bohndorf K, Sohn M, Teufl F, Guenther RW, Daus HJ. Urinary bladder neoplasms: evaluation with contrast-enhanced MR imaging. Radiology. 1989;172:739-43. 10. Sparenberg A, Hamm B, Hammerer P, Samberger V, Wolf KJ. [The diagnosis of bladder carcinomas by NMR tomography: an improvement with Gd-DTPA?]. Rofo. 1991;155:117-22. 11. Sohn M, Neuerburg J, Teufl F, Bohndorf K. Gadolinium- enhanced magnetic resonance imaging in the staging of urinary bladder neoplasms. Urol Int. 1990;45:142-7. 12. Scattoni V, Da Pozzo LF, Colombo R, et al. Dynamic gadolin- ium-enhanced magnetic resonance imaging in staging of superficial bladder cancer. J Urol. 1996;155:1594-9. 13. Tanimoto A, Yuasa Y, Imai Y, et al. Bladder tumor staging: comparison of conventional and gadolinium-enhanced dynamic MR imaging and CT. Radiology. 1992;185:741-7. 14. Sutton D. Textbook of Radiology and Imaging. 7 ed: Churchill Livingstone; 2003;31:1008-10. 15. Narumi Y, Kadota T, Inoue E, et al. Bladder tumors: staging with gadolinium-enhanced oblique MR imaging. Radiol- ogy. 1993;187:145-50. 16. Hayashi N, Tochigi H, Shiraishi T, Takeda K, Kawamura J. A new staging criterion for bladder carcinoma using gadolinium-enhanced magnetic resonance imaging with an endorectal surface coil: a comparison with ultrasonog- raphy. BJU Int. 2000;85:32-6. 17. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666-75. 18. Abou-El-Ghar ME, El-Assmy A, Refaie HF, El-Diasty T. Bladder cancer: diagnosis with diffusion-weighted MR imaging in patients with gross hematuria. Radiology. 2009;251:415-21. REFERENCES 1. Barentsz JO, Jager GJ, van Vierzen PB, et al. Staging urinary bladder cancer after transurethral biopsy: value of fast dynamic contrast-enhanced MR imaging. Radiology. 1996;201:185-93. 2. Greene FL, Compton CC, Fritz AG, Shah JP, Winchester DP. AJCC cancer staging atlas. Berlin, Germany: Springer; 2006. 3. Kim B, Semelka RC, Ascher SM, Chalpin DB, Carroll PR, Hricak H. Bladder tumor staging: comparison of contrast- enhanced CT, T1- and T2-weighted MR imaging, dynamic gadolinium-enhanced imaging, and late gadolinium- enhanced imaging. Radiology. 1994;193:239-45. 4. Tekes A, Kamel I, Imam K, et al. Dynamic MRI of bladder cancer: evaluation of staging accuracy. AJR Am J Roent- genol. 2005;184:121-7. 5. Sharma S, Ksheersagar P, Sharma P. Diagnosis and treat- ment of bladder cancer. Am Fam Physician. 2009;80:717-23. 6. Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374:239-49. 7. Takeuchi M, Sasaki S, Ito M, et al. Urinary bladder cancer: diffusion-weighted MR imaging--accuracy for diagnos- ing T stage and estimating histologic grade. Radiology. 2009;251:112-21. T2 and lower tumors with stage T3 and higher tumors. They also concluded that despite the belief that tumor contours could be evaluated more accurately by DW images, this tech- nique did not improve MRI accuracy in detecting extravesi- cal involvement in their study.(7) Tekes and coworkers report- (4) CONCLUSION Despite some differences between MRI and histopathology results, MRI could be an acceptable modality for bladder cancer staging. Improvement of MRI techniques and utiliza- accuracy.(4) ACKNOWLEDGEMENTS This study was founded by a medical research grant from the research deputy of Tehran University of Medical Sciences. CONFLICT OF INTEREST None declared.