Urinary bladder cancer (UBC) is dominantly the cancer of the elderly occurring primarily in the 6th, 7th and 8th decade
of life. The aim of this study was to evaluate diagnostic accuracy of ultrasound T-staging (UTS) of UBC in the group of
elderly patients. In 152 elderly patients referred to transabdominal ultrasound examination in two different facilities (76
each) due to various symptoms (primarily painless gross or microscopic haematuria) UBC was diagnosed. Initial UTS
at the moment of detection was performed and compared with fi nal histological T-staging (HTS). A high level of conformity
between UTS and HTS was detected. In a total of 152 patients with UBC there were 115 (75.66%) patients with complete
match between the UTS and HTS, 24 (15.79%) patients with minimal variation within one stage, and 13 (8.55%) patients
with one stage difference between the UTS and HTS. The best result was established for the stage T1, where the accuracy
was 94.5%. In other stages the accuracy was between 84.9% and 91.8%. The Youden’s index for all the stages was over
0.6. UTS has a high diagnostic accuracy, especially for stages T1 and T2. It is extremely useful tool in differentiating the
superfi cial UBC from the muscle-invasive one, being of signifi cant importance in planning the further treatment of elderly
patients and having important role in choosing appropriate surgical approach

Dražen Rahelić

Stanislav Sotošek

Tomislav Tadin

Željko Fučkar

English

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1123T. Tadin et al.: Ultrasound T-staging of the Urinary Bladder Cancer, Coll. Antropol. 38 (2014) 4: 1123–1126transabdominal ultrasound examination due to various symptoms, primarily painless gross or microscopic hae-maturia in 60.52% and dysuria 28.94%. At the moment of detection of UBC all the patients underwent initial UTS of the tumour as illustrated in Figures 1 and 2. The post-operative histological fi ndings were analysed and fi nal HTS was compared with initial UTS at the moment of detection. The study was carried out in full accordance with ethical standards applicable in both institutions.StatisticsThe primary method in comparison of UTS and HTS was ROC analysis, where HTS was taken as reference diagnosis. The basic parameter for assessing the accuracy of diagnosis was the quotient calculated as the sum of true negative ones and true positive ones divided by the total Diagnostic accuracy of ultrasound T-staging (UTS) of the urinary bladder cancer (UBC) has permanently been a challenging issue in clinical practice, since the proper initial staging of the tumour is essential for further treat-ment1. Therefore, the comparison of initial UTS with the fi nal histological T-staging (HTS) provides the best pos-sible evaluation of the quality of initial UTS at the moment of detection of UBC. In this paper we report on the results of the retrospective study on diagnostic accuracy of UTS of UBC.Materials and MethodsA sample of 152 patients with UBC examined at two different ultrasound diagnostic centres (76 in each) was analysed with respect to initial UTS and later HTS. All the patients (108 males and 44 females) were referred to Coll. Antropol. 38 (2014) 4: 123–11Original scientifi c paperDiagnostic Accuracy of Ultrasound T-staging of the Urinary Bladder Cancer in Comparison with Histology in Elderly PatientsTomislav Tadin1, Stanislav Sotošek2, Dražen Rahelić2 and Željko Fučkar31 Ultrasound Diagnostic Service, Health Centre Rijeka, Rijeka, Croatia2 Department of Urology, University Hospital Centre Rijeka, Rijeka, Croatia3 Faculty of Medicine, University of Rijeka, Rijeka, CroatiaA B S T R A C TUrinary bladder cancer (UBC) is dominantly the cancer of the elderly occurring primarily in the 6th, 7th and 8th decade of life. The aim of this study was to evaluate diagnostic accuracy of ultrasound T-staging (UTS) of UBC in the group of elderly patients. In 152 elderly patients referred to transabdominal ultrasound examination in two different facilities (76 each) due to various symptoms (primarily painless gross or microscopic haematuria) UBC was diagnosed. Initial UTS at the moment of detection was performed and compared with fi nal histological T-staging (HTS). A high level of conform-ity between UTS and HTS was detected. In a total of 152 patients with UBC there were 115 (75.66%) patients with complete match between the UTS and HTS, 24 (15.79%) patients with minimal variation within one stage, and 13 (8.55%) patients with one stage difference between the UTS and HTS. The best result was established for the stage T1, where the accuracy was 94.5%. In other stages the accuracy was between 84.9% and 91.8%. The Youden’s index for all the stages was over 0.6. UTS has a high diagnostic accuracy, especially for stages T1 and T2. It is extremely useful tool in differentiating the superfi cial UBC from the muscle-invasive one, being of signifi cant importance in planning the further treatment of eld-erly patients and having important role in choosing appropriate surgical approach.Key words: cancer, T-staging, urinary bladder, ultrasound, elderlyIntroductionReceived for publication June 11, 20141124T. Tadin et al.: Ultrasound T-staging of the Urinary Bladder Cancer, Coll. Antropol. 38 (2014) 4: 1123–1126number of patients. We also provided the other important parameters such as sensitivity, specifi city, positive predic-tive accuracy and negative predictive accuracy. In order to study the overall performance of a test we provided kappa agreement measure and Youden’s index. The qual-ity of test was also tested with Chi-square test. The sta-tistical analysis was performed by independent company, ID Consulting, Bribir, Croatia.ResultsIn 152 patients both initial UTS and fi nal HTS of UBC were determined. The fi ndings were compared and the level of their match was determined as presented in Fig-ure 3.Comparative analysis of the above results shows that in 115 (75.66%) patients there was a complete match be-tween the UTS and HTS, in 24 (15.79%) patients there was a minimal variation within one stage, and in 13 (8.55%) patients there was one stage difference between the UTS and HTS. In Table 1 statistical parameters are presented.Diagnostic accuracy of UTS was rather high for stages T1 and T2, while it was slightly lower for the stages T3 and T4. Furthermore, diagnostic accuracy was particu-larly low for ultrasound differentiation between stages T3a and T3b. Nevertheless, diagnostic accuracy for com-mon stage T3 was still suffi cient enough in comparison with diagnostic accuracy for other stages. Therefore, the stages T3a and T3b shall not be taken into consideration separately in further discussion. Generally high specifi -city was accompanied with slightly lower sensitivity, espe-cially for stage T1, but Youden’s index in all cases is above satisfactory value of 0.6. Positive predictive accuracy was relatively lower for stage T2, and negative predictive ac-curacy was slightly lower for stage T3. For other stage these two parameters were relatively high, especially the negative predictive accuracy.In all relevant cases Kappa agreement measure was above 0.65. Therefore, we have good agreement between provided diagnostic methods. Chi square test also showed that it was unlikely that the observed results were caused by chance.DiscussionRather high diagnostic accuracy for stages T1 and T2, and slightly lower accuracy for the stages T3 and T4 can be explained by the fact that deeper penetration of the tumour always involves obstacles in maintaining initial ultrasound precision of evaluation, particularly in assess-ing the penetration into surrounding structures. Particu-Fig. 3. Initial ultrasound T-staging and fi nal histological T-staging of the urinary bladder cancer.Fig. 1. Male, 62, with the only symptom being painless gross hae-maturia and with urinary bladder cancer on the left lateral wall of the bladder with superfi cial infi ltration of the subepithelial connective tissue living intact muscle layer. The initial ultra-sound T-staging at the moment of detection was T1. The fi nal histological T-staging was pT1.Fig. 2. Female, 58, with the only symptom being painless gross haematuria, and with urinary bladder cancer on the left lateral wall of the bladder, being muscle-invasive with initial infi ltration of the inner half of the muscle layer (arrows). The initial ultra-sound T-staging at the moment of detection was T2. The fi nal histological T-staging was pT2.1125T. Tadin et al.: Ultrasound T-staging of the Urinary Bladder Cancer, Coll. Antropol. 38 (2014) 4: 1123–1126larly low diagnostic accuracy between stages T3a and T3b can be explained partly by insuffi cient ultrasound differ-entiation of these two sub-stages of tumour penetration, and, in some cases, by time gap between initial ultrasound detection and fi nal histological analysis. On the other hand, diagnostic accuracy for common stage T3 was suf-fi cient to make this stage distinctive enough in compari-son with other stages.High specifi city for stage T1 was accompanied with its relatively low sensitivity. Indeed, seeing the ultrasound difference between tumorous infi ltration of the subepithe-lial connective tissue in T1 and initial tumorous infi ltra-tion of the muscular layer in T2 is possible in most of the cases with limited certainty (Fig. 1 & 2). On the other hand, detection of early forms, like Ta and T1, sometimes may be facing limitations due to insuffi cient visibility, which was also confi rmed by Khan et al.2.However, insuffi cient visibility was a serious obstacle in certain number of cases. Therefore, a small number of tumours initially UTS classifi ed as T1 were fi nally HTS classifi ed as T2. In some case, time gap between UTS and HTS should be considered as a factor, as well. Slightly lower positive predictive accuracy for stage T2 can be ex-plained by some borderline cases in which either fi nal histological correction or progression of the fi nding took place till the moment of histological evaluation. After all, although operative treatment is always applied as soon as possible UTS and HTS are not simultaneous actions.The slightly negative predictive accuracy for T3 can be explained by insuffi cient visibility in some cases that re-duces the assessment of the extent of muscle infi ltration versus T2 or extent of possibly deep penetration into sur-rounding structures versus T4, often accompanied by dis-tant metastases3. Furthermore, Denkhaus et al. reported on sonographic staging being correct in 83% of all tumour stages but with the lowest value of 69% for T2/T3a tu-mours4. The latter one is particularly important from the surgical point of view because most of the patients under-going radical surgical treatment are those with stages T3 and T25.Although Tsakiris and de la Rosette1 agree that proper staging of the tumour is essential for further treatment emphasising that the fi rst aspect that has to be considered is whether the patient has a superfi cial or a muscle-inva-sive tumour, they fi nd the role of imaging in T-staging being not that essential. On the contrary, the results of this study showed that preoperative UTS was extremely useful in determining further procedure being very ac-curate in making difference between stages T1 and T2. On the other hand, the results of this study confi rmed low diagnostic accuracy of UTS in stages T3 and T4 because of the limited ability to evaluate the perivesical tissue, as earlier reported by Lantz and Hattery6 and by Barentz et al.7.The results of this study are rather consistent with large study of Fang et al.8 comparing the UTS with HTS showing 78.5% of total accuracy. McLaughlin et al. also TABLE 1ACCURACY OF ULTRASOUND T-STAGING OF THE URINARY BLADDER CANCER IN COMPARISON WITH HISTOLOGI-CAL T-STAGINGStages T1 T2 T3a T3b T3 T4Accuracy0.94595% CI: 0.898,0.992]0.91895% CI:[0.861, 0.975]0.78195% CI:[0.695, 0.866]0.82295% CI:[0.743, 0.901]0.84995% CI:[0.775, 0.923]0.84995% CI:[0.775, 0.923]Kappaagreementmeasure0.68595% CI:[0.48,0.889]0.65395% CI:[0.447, 0.858]0.3695% CI:[0.154, 0.567]0.38395% CI:[0.187, 0.578]0.68595% CI:[0.48, 0.89]0.68195% CI:[0.476, 0.885]Sensitivity0.62595% CI:[0.322,0.928]0.77895% CI:[0.533, 1.023]0.53395% CI:[0.306, 0.761]0.37595% CI:[0.161, 0.589]0.74295% CI:[0.603, 0.881]0.8895% CI:[0.765, 0.995]Specifi city0.98595% CI:[0.958,1.012]0.93895% CI:[0.884, 0.991]0.84595% CI:[0.761, 0.929]0.94795% CI:[0.895, 1]0.92995% CI:[0.858, 0.999]0.83395% CI:[0.738, 0.928]Youden’s J0.6195% CI:[0.306,0.913]0.71595% CI:[0.465, 0.966]0.37895% CI:[0.135, 0.621]0.32295% CI:[0.102, 0.543]0.67195% CI:[0.515, 0.826]0.71395% CI:[0.564, 0.862]Positivepredictiveaccuracy0.83395% CI:[0.564,1.102]0.63695% CI:[0.38, 0.893]0.47195% CI:[0.257, 0.685]0.66795% CI:[0.389, 0.944]0.88595% CI:[0.774, 0.995]0.73395% CI:[0.591, 0.876]Negativepredictiveaccuracy0.95595% CI:[0.911,1]0.96895% CI:[0.928, 1.007]0.87595% CI:[0.797, 0.953]0.84495% CI:[0.764, 0.924]0.8395% CI:[0.733, 0.927]0.9395% CI:[0.862, 0.999]Chi square 70.185(p<0.001)63.087(p<0.001)19.08(p<0.001)24.023(p<0.001)69.936(p<0.001)69.108(p<0.001)1126T. Tadin et al.: Ultrasound T-staging of the Urinary Bladder Cancer, Coll. Antropol. 38 (2014) 4: 1123–1126confi rmed a high degree of accuracy in staging by ultra-sound9. The study of Caskurlu et al. found transabdominal ultrasound having sensitivity and specifi city of 72.2% in the superfi cial tumours, and sensitivity of 65% and spe-cifi city of 70% for infi ltrating tumours of the urinary blad-der10. On the other hand, the overall accuracy of three-dimensional UTS reported by Wagner et al.11 was 79%. The latest research of Masumbuko and Sydney12 reported the overall sensitivity, specifi city, positive predictive val-ue, and negative predictive value of ultrasound in detec-tion of UBC 83%, 93%, 89% and 89%, respectively.Furthermore, recently published study of Xu et al.13 on the use of fl exible ultrasound bronchoscope (FUB) in blad-der tumour staging had excellent results with overall ac-curacy (95.7%) and the specifi city of muscle invasion detec-tion of FUB (98.8%) being comparable to transurethral resection (overall accuracy 90.2% and specifi city 100%), and with sensitivity of the muscle invasion detection of FUB being signifi cantly higher than in initial TUR (72.7%VS18.2%). Moreover, the tumour’s diameter could not affect the FUB’s accuracy of muscle invasion detec-tion. This promising new tool could be a break-through in future ultrasound staging of the primary tumour.ConclusionDiagnostic accuracy of UTS is high for stages T1 and T2, slightly lower for stages T3 and T4, and insuffi cient in differentiation between stages T3a and T3b. Therefore, it is extremely useful in initial assessment of newly detected UBC with respect to differing superfi cial tumour from the muscle-invasive one which is essential for planning the further treatment14. Furthermore, it is highly useful non-invasive tool for assessing the penetration of UBC into surrounding structures.R E F E R E N C E S1. TSAKIRIS P, DE LA ROSETTE J, Cancer Imaging, 7 (2007) 84. DOI: 10.1102/1470-7330.2007.0009. — 2. KHAN AN, CHANDRAMO-HAN H, MACDONALD S, Transitional Cell Carcinoma Imaging, ac-cessed 10.6.2014. Available from: http://emedicine.medscape.com/article/381323-overview. — 3. PETKOVIĆ M, MUHVIĆ D, ZAMOLO G, JONJIĆ N, MUSTAĆ E, MRAKOVČIĆ-ŠUTIĆ I, SEILI-BEKAFIGO I, Coll Antropol, 28 (2004) 337. — 4. DENKHAUS H, CRONE-MÜNZE-BROCK W, HULAND H, Urol Radiol, 1 (1985) 121. — 5. MARIČIĆ A, VALENČIĆ M, OGUIĆ R, RAHELIĆ D, KRPINA K, MATERLJAN M, Coll Antropol, 34 (2010) 223. — 6. LANTZ EJ, HATTERY RR, Urol Clin North Am, 11 (1984) 583 — 7. BARENTSZ JO, ENGELBRECHT MR, WITJES JA, DE LA ROSETTE JJ, VAN DER GRAAF M, Eur Radiol, 9 (1999) 1722. — 8. FANG YC, CHOU YH, HSU CC, CHANG T, Zhonghua Yi Xue Za Zhi (Taipei), 52 (1993) 21. — 9. MCLAUGHLIN IS, MORLEY P, DEANE RF, BARNETT E, GRAHAM EG, KYLE KF, Br J Urol, 47 (1975) 51. — 10. CASKURLU T, TASCI AL, SEVIN G, CEK M, CAR-BONE A, GEZEROGLU H, Arch Ital Urol Androl, 70 (1998) 1. — 11. WAGNER B, NESSLAUER T, BARTSCH G JR, HAUTMANN RE, GOTTFRIED HW, Ultrasound Med Biol, 31 (2005) 301. — 12. MAS-UMBUKO YM, SYDNEY CY, Tanzan J Health Res, 13 (2011) 1. — 13. XU C, ZHANG Z, WANG H, SONG Q, WEI R, YU Y, LI J, SUN Y, PLoS_One, 9 (2014) 92385. DOI: 10.1371/journal.pone.0092385. eCollection 2014. — 14. TADIN T, Ultrasound Detection of the Urinary Bladder Can-cer in Daily Practice. In: Abstracts of 24th European Congress of Ultra-sound (Euroson, Madrid, 2012).T. TadinDr. Zdravka Kučića 27, 51000 Rijeka, Croatiae-mail: medicina_ri@inet.hrDIJAGNOSTIČKA TOČNOST ULTRAZVUČNOG T-STUPNJEVANJA KARCINOMA MOKRAĆNOG MJEHURA U USPOREDBI S PATOHISTOLOŠKIM NALAZOMS A Ž E T A KKarcinom mokraćnog mjehura (KMM) je dominantno karcinom starije dobi koji se primarno razvija u 6., 7. i 8. desetljeću života. Cilj ovog istraživanja bio je procijeniti dijagnostičku točnost ultrazvučnog T-stupnjevanja (UTS) KMM-a u skupini starijih bolesnika. U 152 starijih bolesnika koji su upućeni na trasabdominalni ultrazvučni pregled u dvjema različitim ustanovama (76 u svakoj) zbog različitih simptoma (prvenstveno bezbolne makro- ili mikro- hematurije) dij-agnosticiran je KMM. Početno UTS učinjeno je u trenutku otkrivanja i uspoređeno s konačnim histološkim T-stupnjevan-jem (HTS). Nađena je visoku podudarnost između UTS-a i HTS-a. Od ukupno 152 pacijenata s KMM-om bilo je 115 (75,66%) bolesnika s potpunim podudaranjem UTS-a i HTS-a, 24 (15,79%) s minimalnim varijacijom unutar jednog stupnja i 13 (8,55%) pacijenata s razlikom od jednog stupnja između UTS-a i HTS-a. Najbolji rezultat je utvrđen za stupanj T1, gdje je točnost iznosila 94,5%. U drugim stupnjevima točnost se kretala između 84,9% i 91,8%. Yudenov indeks za sve stupnjeve iznosio je preko 0,6. UTS ima visoku dijagnostičku točnost, posebno za stupnjeve T1 i T2. Ono je izrazito korisno sredstvo u diferencijaciji površinskog KMM-a od mišićno-invazivnog i od velike je važnosti u plani-ranju daljnjeg liječenja pacijenata imajući važnu ulogu u odabiru pravilnog kirurškog pristupa.

Diagnostic Accuracy of Ultrasound T-staging of the Urinary Bladder Cancer in Comparison with Histology in Elderly Patients

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