Background: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk. Objective: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score. Materials and Methods: Clinical and histopathological characteristics and CSS of 150 patients were assessed. Secondary MIBCs were stratified by EORTC risk score at the last transurethral resection of bladder tumour for NMIBC. Results: CSS did not differ significantly between primary and secondary MIBC (p = 0.521). Secondary MIBC with high EORTC score had significantly shorter CSS compared to secondary MIBC with intermediate EORTC score (p = 0.029). In multivariable analysis, pathological tumour stage (HR = 3.77; p = 0.020) and lymph node stage (HR = 2.34; p = 0.022) were significantly correlated with CSS. Conclusion: While the outcome of secondary MIBC is not generally adverse compared to primary MIBC, the EORTC risk score not only reflects high risk of progression of NMIBC to MIBC, but also worse outcome following RC for secondary MIBC. Timely RC should thus be debated in high-risk NMIBC.

Keywords:
Bladder cancer, Risk stratification, EORTC risk tables, Prognosis, Progression, Radical cystectomy
1.
Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y: Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63:234-241.
2.
Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J, Rouprêt M; European Association of Urology (EAU): EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 2011;59:997-1008.
3.
Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth K: Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49:466-475; discussion 475-477.
4.
Altieri VM, Castellucci R, Palumbo P, Verratti V, Sut M, Olivieri R, Manco R, Ricciardulli S, Nicolai M, Criniti P, Tenaglia RL: Recurrence and progression in non-muscle-invasive bladder cancer using EORTC risk tables. Urol Int 2012;89:61-66.
5.
Gakis G, Schwentner C, Todenhoefer T, Stenzl A: Current status of molecular markers for prognostication and outcome in invasive bladder cancer. BJU Int 2012;110:233-237.
6.
Shapur N, Pode D, Katz R, Shapiro A, Yutkin V, Pizov G, Appelbaum L, Zorn KC, Duvdevani M, Landau EH, Gofrit ON: Predicting the risk of high-grade bladder cancer using noninvasive data. Urol Int 2011;87:319-324.
7.
Badalato GM, Gaya JM, Hruby G, Patel T, Kates M, Sadeghi N, Benson MC, McKiernan JM: Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference? BJU Int 2012;110:1471-1477.
8.
Jäger W, Thomas C, Haag S, Hampel C, Salzer A, Thüroff JW, Wiesner C: Early vs delayed radical cystectomy for ‘high-risk' carcinoma not invading bladder muscle: delay of cystectomy reduces cancer-specific survival. BJU Int 2011;108:E284-E288.
9.
Segal R, Yafi FA, Brimo F, Tanguay S, Aprikian A, Kassouf W: Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy? BJU Int 2012;109:1026-1030.
10.
Denzinger S, Fritsche HM, Otto W, Blana A, Wieland WF, Burger M: Early versus deferred cystectomy for initial high-risk pT1G3 urothelial carcinoma of the bladder: do risk factors define feasibility of bladder-sparing approach? Eur Urol 2008;53:146-152.
11.
Matsumoto K, Kikuchi E, Shirakawa H, Hayakawa N, Tanaka N, Ninomiya A, Miyajima A, Nakamura S, Oya M: Risk of subsequent tumour recurrence and stage progression in bacille Calmette-Guérin relapsing non-muscle-invasive bladder cancer. BJU Int 2012;110:E508-E513.
12.
Lee CT, Madii R, Daignault S, Dunn RL, Zhang Y, Montie JE, Wood DP Jr: Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival. J Urol 2006;175:1262-1267; discussion 1267.
13.
Fahmy NM, Mahmud S, Aprikian AG: Delay in the surgical treatment of bladder cancer and survival: systematic review of the literature. Eur Urol 2006;50:1176-1182.
14.
May M, Nitzke T, Helke C, Vogler H, Hoschke B: Significance of the time period between diagnosis of muscle invasion and radical cystectomy with regard to the prognosis of transitional cell carcinoma of the urothelium in the bladder. Scand J Urol Nephrol 2004;38:231-235.
15.
Greene FL, Gospodarowicz M, Wittekind C, et al: American Joint Committee on Cancer (AJCC) Staging Manual, ed 7. Philadelphia, Springer, 2009.
16.
Sauter G, Algaba F, Amin M, et al: Tumours of the urinary system: non-invasive urothelial neoplasias; in Eble JN, Sauter G, Epstein Jl, Sesterhenn I (eds): WHO Classification of Tumors of the Urinary System and Male Genital Organs. Lyon, IARCC Press, 2004, pp 29-34.
17.
Yiou R, Patard JJ, Benhard H, Abbou CC, Chopin DK: Outcome of radical cystectomy for bladder cancer according to the disease type at presentation. BJU Int 2002;89:374-378.
18.
May M, Helke C, Nitzke T, Vogler H, Hoschke B: Survival rates after radical cystectomy according to tumour stage of bladder carcinoma at first presentation. Urol Int 2004;72:103-111.
19.
de Vries RR, Nieuwenhuijzen JA, Vincent A, van Tinteren H, Horenblas S: Survival after cystectomy for invasive bladder cancer. Eur J Surg Oncol 2010;36:292-297.
20.
Kotb AF, Kovac E, Kassouf W, Chin J, Fradet Y, Izawa J, Estey E, Fairey A, Rendon R, Cagiannos I, Lacombe L, Lattouf JB, Bell D, Drachenberg D, Aprikian AG: Radical cystectomy for clinically muscle invasive bladder cancer: does prior non-invasive disease affect clinical outcomes? World J Urol 2012;30:761-767.
21.
Lee CT, Dunn RL, Ingold C, Montie JE, Wood DP Jr: Early-stage bladder cancer surveillance does not improve survival if high-risk patients are permitted to progress to muscle invasion. Urology 2007;69:1068-1072.
22.
Turker P, Bostrom PJ, Wroclawski ML, van Rhijn B, Kortekangas H, Kuk C, Mirtti T, Fleshner NE, Jewett MA, Finelli A, Kwast TV, Evans A, Sweet J, Laato M, Zlotta AR: Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome. BJU Int 2012;110:804-811.
23.
Otto W, Denzinger S, Fritsche HM, Burger M, Wieland WF, Hofstädter F, Hartmann A, Bertz S: The WHO classification of 1973 is more suitable than the WHO classification of 2004 for predicting survival in pT1 urothelial bladder cancer. BJU Int 2011;107:404-408.
24.
van Rhijn BW, Liu L, Vis AN, Bostrom PJ, Zuiverloon TC, Fleshner NE, van der Aa MN, Alkhateeb SS, Bangma CH, Jewett MA, Zwarthoff EC, Bapat B, van der Kwast TH, Zlotta AR: Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int 2012;110:1169-1176.
25.
Bertz S, Denzinger S, Otto W, Wieland WF, Stoehr R, Hofstaedter F, Hartmann A: Substaging by estimating the size of invasive tumour can improve risk stratification in pT1 urothelial bladder cancer - evaluation of a large hospital-based single-centre series. Histopathology 2011;59:722-732.
26.
Bertz S, Otto W, Denzinger S, Wieland WF, Burger M, Stöhr R, Link S, Hofstädter F, Hartmann A: Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Eur Urol 2012, Epub ahead of print.
27.
Rink M, Cha EK, Green D, Hansen J, Robinson BD, Lotan Y, Sagalowsky AI, Chun FK, Karakiewicz PI, Fisch M, Scherr DS, Shariat SF: Biomolecular predictors of urothelial cancer behavior and treatment outcomes. Curr Urol Rep 2012;13:122-135.
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2013
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