Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press58810.17650/1726-9776-2016-12-4-119-130DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCERДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ МОЧЕПОЛОВОЙ СИСТЕМЫ. Рак мочевого пузыряAssessment of recurrence and progression risk in patients with non-muscle invasive bladder cancerОценка риска рецидивирования и прогрессирования при раке мочевого пузыря без мышечной инвазииRolevichA. I.РолевичА. И.
Belarus

Lesnoy Village, Minsk Region, 223040

223040, Минский район, агрогородок Лесной

alexander.rolevich@gmail.comMirilenkoL. V.МириленкоЛ. В.
Belarus

Lesnoy Village, Minsk Region, 223040

223040, Минский район, агрогородок Лесной

State Institution N.N. Alexandrov National Cancer CentreГУ «Республиканский научно-практический центр онкологии и медицинской радиологии им. Н.Н. Александрова»301220161241191301807201618102016https://oncourology.abvpress.ru/oncur/article/view/588

A retrospective analysis of monitoring of patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) treated with transurethral resection (TUR) with or without restaging TUR or intravesical therapy in State Institution N.N. Alexandrov National Cancer Centre of Belarus in 2004–2012 was performed with an objective to develop a prognostic classification for NMIBC. The analysis included 921 patients. In the multivatiate analysis independent predictors of recurrence were recurrence rate, number of tumors, tumor size, grade, and tumor location in the trigone, anterior wall, dome, and prostatic urethra; predictors of progression were age, recurrence rate, tumor size, grade, and tumor location in the trigone and prostatic urethra. The patients were divided into 4 groups with low, intermediate, high and very high risk. Corrected C-index values for the developed classifications of recurrence and progression risks were 0.635 and 0.740 respectively, which were significantly higher than C-indices for the European Organization for Research and Treatment of Cancer tables.

Для разработки прогностической классификации рака мочевого пузыря без мышечной инвазии (РМПБМИ) ретроспективно были проанализированы результаты наблюдения за пациентами с первичным или рецидивным РМПБМИ, леченными с использованием трансуретральной резекции (ТУР) с рестадирующей ТУР или без или внутрипузырной терапии в РНПЦ ОМР им. Н.Н. Александрова в период с 2004 по 2012 гг. В исследование включен 921 пациент. В мультивариантном анализе независимыми предикторами развития рецидива были частота рецидивирования, число опухолей, размер образования, степень дифференцировки и локализация опухоли в области треугольника, передней стенки, дна и простатической части уретры; предикторами прогрессирования – возраст, частота рецидивирования, размер опухоли, степень дифференцировки и локализация в области треугольника и простатической части уретры. Все пациенты были разделены на 4 группы: благоприятного, промежуточного, неблагоприятного и крайне неблагоприятного прогноза. Скорректированные показатели С-индексов для разработанных классификаций риска рецидивирования и прогрессирования составили 0,635 и 0,740 соответственно, что было существенно выше, чем С-индексы для таблиц Европейской организации по исследованию и лечению рака.

non-muscle invasive bladder cancerrecurrenceprogressionprognostic classificationрак мочевого пузыря без мышечной инвазиирецидивпрогрессированиепрогностическая классификация1. Burger M., Catto J.W., Dalbagni G. et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63(2):234–41. DOI: 10.1016/j.eururo.2012.07.033. PMID: 22877502.Burger M., Catto J.W., Dalbagni G. et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63(2):234–41. DOI: 10.1016/j.eururo.2012.07.033. PMID: 22877502.2. van Rhijn B.W., Burger M., Lotan Y. et al. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol 2009;56(3):430–42. DOI: 10.1016/j.eururo.2009.06.028. PMID: 19576682.van Rhijn B.W., Burger M., Lotan Y. et al. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol 2009;56(3):430–42. DOI: 10.1016/j.eururo.2009.06.028. PMID: 19576682.3. Gontero P., Bohle A., Malmstrom P.U. et al. The role of bacillus Calmette–Guérin in the treatment of non-muscle-invasive bladder cancer. Eur Urol 2010;57(3):410–29. DOI: 10.1016/j.eururo.2009.11.023. PMID: 19969411.Gontero P., Bohle A., Malmstrom P.U. et al. The role of bacillus Calmette–Guérin in the treatment of non-muscle-invasive bladder cancer. Eur Urol 2010;57(3):410–29. DOI: 10.1016/j.eururo.2009.11.023. PMID: 19969411.4. Babjuk M., Burger M., Zigeuner R. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 2013;64(4):639–53. DOI: 10.1016/j.eururo.2013.06.003. PMID: 23827737.Babjuk M., Burger M., Zigeuner R. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 2013;64(4):639–53. DOI: 10.1016/j.eururo.2013.06.003. PMID: 23827737.5. Sylvester R.J., van der Meijden A.P., Oosterlinck W. et al. 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(3):466–5. DOI: 10.1016/j.eururo.2005.12.031. PMID: 16442208.Sylvester R.J., van der Meijden A.P., Oosterlinck W. et al. 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(3):466–5. DOI: 10.1016/j.eururo.2005.12.031. PMID: 16442208.6. Fernandez-Gomez J., Madero R., Solsona E. et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette–Guerin: the CUETO scoring model. J Urol 2009;182(5):2195–203. DOI: 10.1016/j.juro.2009.07.016. PMID: 19758621.Fernandez-Gomez J., Madero R., Solsona E. et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette–Guerin: the CUETO scoring model. J Urol 2009;182(5):2195–203. DOI: 10.1016/j.juro.2009.07.016. PMID: 19758621.7. Xylinas E., Kent M., Kluth L. et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer 2013;109(6):1460–6. DOI: 10.1038/bjc.2013.372. PMID: 23982601.Xylinas E., Kent M., Kluth L. et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer 2013;109(6):1460–6. DOI: 10.1038/bjc.2013.372. PMID: 23982601.8. Vedder M.M., Márquez M., de BekkerGrob E.W. et al. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours. PLoS One 2014;9(6):e96849. DOI: 10.1371/journal.pone.0096849. PMID: 24905984.Vedder M.M., Márquez M., de BekkerGrob E.W. et al. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours. PLoS One 2014;9(6):e96849. DOI: 10.1371/journal.pone.0096849. PMID: 24905984.9. Ролевич А.И. Внешняя валидизация прогностических схем при раке мочевого пузыря без мышечной инвазии. Здравоохранение 2016 (в печати). [Rolevich А.I. External validization of prognostic schedules at the bladder cancer without muscular invasion. Zdravookhranenie = Healthcare 2016 (being printed). (In Russ.)].Ролевич А.И. Внешняя валидизация прогностических схем при раке мочевого пузыря без мышечной инвазии. Здравоохранение 2016 (в печати). [Rolevich А.I. External validization of prognostic schedules at the bladder cancer without muscular invasion. Zdravookhranenie = Healthcare 2016 (being printed). (In Russ.)].10. Schemper M., Smith T.L. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996;17(4): 343–6. PMID: 8889347.Schemper M., Smith T.L. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996;17(4): 343–6. PMID: 8889347.11. Harrell F.E. Jr, Lee K.L., Mark D.B. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996;15(4):361–87. DOI: 10.1002/(SICI)1097-0258(19960229)15:4<361::AIDSIM168>3.0.CO;2-4. PMID: 8668867.Harrell F.E. Jr, Lee K.L., Mark D.B. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996;15(4):361–87. DOI: 10.1002/(SICI)1097-0258(19960229)15:4<361::AIDSIM168>3.0.CO;2-4. PMID: 8668867.12. Royston P., Sauerbrei W. A new measure of prognostic separation in survival data. Stat Med 2004;23(5):723–48. DOI: 10.1002/sim.1621. PMID: 14981672.Royston P., Sauerbrei W. A new measure of prognostic separation in survival data. Stat Med 2004;23(5):723–48. DOI: 10.1002/sim.1621. PMID: 14981672.13. Vickers A.J., Elkin E.B. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006;26(6):565–74. DOI: 10.1177/0272989X06295361. PMID: 17099194.Vickers A.J., Elkin E.B. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006;26(6):565–74. DOI: 10.1177/0272989X06295361. PMID: 17099194.14. Schröder M.S., Culhane A.C., Quackenbush J., Haibe-Kains B. Survcomp: an R/Bioconductor package for performance assessment and comparison of survival models. Bioinformatics 2011;27(22):3206–8. DOI: 10.1093/bioinformatics/btr511. PMID: 21903630.Schröder M.S., Culhane A.C., Quackenbush J., Haibe-Kains B. Survcomp: an R/Bioconductor package for performance assessment and comparison of survival models. Bioinformatics 2011;27(22):3206–8. DOI: 10.1093/bioinformatics/btr511. PMID: 21903630.15. Vickers A.J., Cronin A.M., Elkin E.B., Gonen M. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 2008;8:53. DOI: 10.1186/1472-6947-8-53. PMID: 19036144.Vickers A.J., Cronin A.M., Elkin E.B., Gonen M. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 2008;8:53. DOI: 10.1186/1472-6947-8-53. PMID: 19036144.16. Millán-Rodríguez F., Chéchile-Toniolo G., Salvador-Bayarri J. et al. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000;164(3 Pt 1):680–4. PMID: 10954628.Millán-Rodríguez F., Chéchile-Toniolo G., Salvador-Bayarri J. et al. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000;164(3 Pt 1):680–4. PMID: 10954628.17. Fernandez-Gomez J., Madero R., Solsona E. et al. The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette–Guérin: external validation of the EORTC risk tables. Eur Urol 2011;60(3):423–30. DOI: 10.1016/j.eururo.2011.05.033. PMID: 21621906.Fernandez-Gomez J., Madero R., Solsona E. et al. The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette–Guérin: external validation of the EORTC risk tables. Eur Urol 2011;60(3):423–30. DOI: 10.1016/j.eururo.2011.05.033. PMID: 21621906.18. Xylinas E., Kent M., Kluth L. et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer 2013;109(6):1460–6. DOI: 10.1038/bjc.2013.372. PMID: 23982601.Xylinas E., Kent M., Kluth L. et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer 2013;109(6):1460–6. DOI: 10.1038/bjc.2013.372. PMID: 23982601.19. Lammers R.J., Palou J., Witjes W.P. et al. Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non-muscleinvasive bladder cancer treated with intravesical chemotherapy. BJU Int 2014;114(2):193–201. DOI: 10.1111/bju.12495. PMID: 24304638.Lammers R.J., Palou J., Witjes W.P. et al. Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non-muscleinvasive bladder cancer treated with intravesical chemotherapy. BJU Int 2014;114(2):193–201. DOI: 10.1111/bju.12495. PMID: 24304638.20. Vedder M.M., Márquez M., de BekkerGrob E.W. et al. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours. PLoS One 2014;9(6):e96849. DOI: 10.1371/journal.pone.0096849. PMID: 24905984.Vedder M.M., Márquez M., de BekkerGrob E.W. et al. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours. PLoS One 2014;9(6):e96849. DOI: 10.1371/journal.pone.0096849. PMID: 24905984.21. Ролевич А.И. Оценка прогностической значимости таблиц EORTC на белорусcкой популяции пациентов, страдающих раком мочевого пузыря без мышечной инвазии. Онкологический журнал 2016 (в печати). [Rolevich А.I. Assessment of the prognostic value of EORTC tables on the Belorussian population of patients with bladder cancer without muscular invasion. Onkologicheskiy zhurnal = Оncologic Journal 2016 (being printed). (In Russ.)].Ролевич А.И. Оценка прогностической значимости таблиц EORTC на белорусcкой популяции пациентов, страдающих раком мочевого пузыря без мышечной инвазии. Онкологический журнал 2016 (в печати). [Rolevich А.I. Assessment of the prognostic value of EORTC tables on the Belorussian population of patients with bladder cancer without muscular invasion. Onkologicheskiy zhurnal = Оncologic Journal 2016 (being printed). (In Russ.)].22. Witjes J.A., Kiemeney L.A., Wheeless L.L., Grossman H.B. The value of histopathological prognostic factors in superficial bladder cancer. Urologic Oncology: Seminars and Original Investigations. Vol 5(5). Pp. 185–190.Witjes J.A., Kiemeney L.A., Wheeless L.L., Grossman H.B. The value of histopathological prognostic factors in superficial bladder cancer. Urologic Oncology: Seminars and Original Investigations. Vol 5(5). Pp. 185–190.23. Tosoni I., Wagner U., Sauter G. et al. Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer. BJU Int 2000;85:48–53. PMID: 10619945.Tosoni I., Wagner U., Sauter G. et al. Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer. BJU Int 2000;85:48–53. PMID: 10619945.24. Mikuz G. The reliability and reproducibility of the different classification of bladder cancer. In book: Surgical Pathology Update. Eds. by: S. Hauptmann, M. Dietel, M. Sorbrinho. 2001. Berlin: ABW-Wissenschaftsverlag, 2001. 114 p.Mikuz G. The reliability and reproducibility of the different classification of bladder cancer. In book: Surgical Pathology Update. Eds. by: S. Hauptmann, M. Dietel, M. Sorbrinho. 2001. Berlin: ABW-Wissenschaftsverlag, 2001. 114 p.25. Набебина Т.И., Ролевич А.И., Дубровский А.Ч. Межисследовательская воспроизводимость определения морфологических параметров при раке мочевого пузыря без мышечной инвазии с неблагоприятным прогнозом. Онкоурология 2016;(1):21–8. [Nabebina T.I., Rolevich A.I., Dubrovskiy A.Ch. Interobserver reproducibility of pathological variables in patients with high grade non-muscle invasive bladder cancer. Onkourologiya = Cancer Urology 2016;(1): 21–8. (In Russ.)].Набебина Т.И., Ролевич А.И., Дубровский А.Ч. Межисследовательская воспроизводимость определения морфологических параметров при раке мочевого пузыря без мышечной инвазии с неблагоприятным прогнозом. Онкоурология 2016;(1):21–8. [Nabebina T.I., Rolevich A.I., Dubrovskiy A.Ch. Interobserver reproducibility of pathological variables in patients with high grade non-muscle invasive bladder cancer. Onkourologiya = Cancer Urology 2016;(1): 21–8. (In Russ.)].26. Stephenson W.T., Holmes F.F., Noble M.J., Gerald K.B. Analysis of bladder carcinoma by subsite. Cystoscopic location may have prognostic value. Cancer 1990;66(7):1630–5. PMID: 2208014.Stephenson W.T., Holmes F.F., Noble M.J., Gerald K.B. Analysis of bladder carcinoma by subsite. Cystoscopic location may have prognostic value. Cancer 1990;66(7):1630–5. PMID: 2208014.27. Segal R., Yafi F.A., Brimo F. et al. Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy? BJU Int 2012;109(7):1026–30. DOI: 10.1111/j.1464-410X.2011.10462.x. PMID: 21883838.Segal R., Yafi F.A., Brimo F. et al. Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy? BJU Int 2012;109(7):1026–30. DOI: 10.1111/j.1464-410X.2011.10462.x. PMID: 21883838.28. Vukomanovic I., Colovic V., Soldatovic I., Hadzi-Djokic J. Prognostic significance of tumor location in high-grade non-muscleinvasive bladder cancer. Med Oncol 2012;29(3):1916–20. DOI: 10.1007/s12032-011-9999-4. PMID: 21656270.Vukomanovic I., Colovic V., Soldatovic I., Hadzi-Djokic J. Prognostic significance of tumor location in high-grade non-muscleinvasive bladder cancer. Med Oncol 2012;29(3):1916–20. DOI: 10.1007/s12032-011-9999-4. PMID: 21656270.29. Mulders P.F., Meyden A.P., Doesburg W.H. et al. Prognostic factors in pTa–pT1 superficial bladder tumours treated with intravesical instillations. The Dutch South-Eastern Urological Collaborative Group. Br J Urol 1994;73(4):403–8. PMID: 8199828.Mulders P.F., Meyden A.P., Doesburg W.H. et al. Prognostic factors in pTa–pT1 superficial bladder tumours treated with intravesical instillations. The Dutch South-Eastern Urological Collaborative Group. Br J Urol 1994;73(4):403–8. PMID: 8199828.30. Palou J., Sylvester R.J., Faba O.R. et al. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and diseasespecific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin. Eur Urol 2012;62(1):118–25. DOI: 10.1016/j.eururo.2011.10.029. PMID: 22101115.Palou J., Sylvester R.J., Faba O.R. et al. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and diseasespecific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin. Eur Urol 2012;62(1):118–25. DOI: 10.1016/j.eururo.2011.10.029. PMID: 22101115.31. Svatek R.S., Clinton T.N., Wilson C.A. et al. Intravesical tumor involvement of the trigone is associated with nodal metastasis in patients undergoing radical cystectomy. Urology 2014;84(5):1147–51. DOI: 10.1016/j.urology.2014.05.011. PMID: 25174656.Svatek R.S., Clinton T.N., Wilson C.A. et al. Intravesical tumor involvement of the trigone is associated with nodal metastasis in patients undergoing radical cystectomy. Urology 2014;84(5):1147–51. DOI: 10.1016/j.urology.2014.05.011. PMID: 25174656.32. Pettus J.A., Al-Ahmadie H., Barocas D.A. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur Urol 2008;53(2): 370–5. PMID: 17689003. DOI: 10.1016/j.eururo.2007.07.031.Pettus J.A., Al-Ahmadie H., Barocas D.A. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur Urol 2008;53(2): 370–5. PMID: 17689003. DOI: 10.1016/j.eururo.2007.07.031.