urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical University10.52420/umj.23.2.54JJPVIGurmj-1496Research ArticleОригинальные статьи | Original articlesOriginal articlesРобот-ассистированная радикальная цистэктомия как современный метод персонифицированного лечения пациентов с мышечно-инвазивным раком мочевого пузыряRobot-Assistant Radical Cystectomy as a Modern Method of Personalized Treatment for Patients with Muscle-Invasive Bladder Cancerhttps://orcid.org/0000-0003-2125-4897ПавловВ. Н.PavlovV. N.

Валентин Николаевич Павлов — доктор медицинских наук, профессор, академик Российской академии наук, ректор, заведующий кафедрой урологии с курсом ИДПО, Башкирский государственный медицинский университет

Уфа

Valentin N. Pavlov — Doctor of Sciences (Medicine), Professor, Full Member (Academician) of the Russian Academy of Sciences, Rector, Head of the Department of Urology with the course of IAPE

Ufa

pavlov@bashgmu.ruhttps://orcid.org/0000-0002-4657-6625УрманцевМ. Ф.UrmantsevM. F.

Марат Фаязович Урманцев — кандидат медицинских наук, доцент кафедры урологии с курсом ИДПО

Уфа

Marat F. Urmantsev — Candidate of Sciences (Medicine), Associate Professor of the Department of Urology with the course of IAPE

Ufa

urmantsev85@mail.ruhttps://orcid.org/0000-0002-4160-2820БакеевМ. Р.BakeevM. R.

Марат Радикович Бакеев — студент лечебного факультета

 Уфа

Marat R. Bakeev — Specialist’s Degree Student of the Faculty of the General Medicine

Ufa

m.r.bakeev@bk.ruБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian Federation2024080520242325464Copyright © Павлов В.Н., Урманцев М.Ф., Бакеев М.Р., 20242024Павлов В.Н., Урманцев М.Ф., Бакеев М.Р.Pavlov V.N., Urmantsev M.F., Bakeev M.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/1496Введение

Введение. Радикальная цистэктомия (РЦ) является «золотым стандартом» лечения мышечно-инвазивного рака мочевого пузыря (МИРМП). Робот-ассистированная РЦ (РАРЦ) в сочетании с методами клеточной диагностики может выступать безопасным и эффективным способом лечения МИРМП.

Цель исследования — анализ собственного опыта применения РАРЦ с интраоперационной флуоресценцией индоцианином зеленым (ICG) и послеоперационным определением уровней опухолевых макрофагов при лечении пациентов с МИРМП.

Материалы и методы

Материалы и методы. В Клинике Башкирского государственного медицинского университета проведено исследование с участием 202 пациентов после РАРЦ по поводу МИРМП. 30 пациентам выполнялась интраоперационная ICG-флуоресценция. У всех пациентов определялись уровни опухолевых макрофагов в удаленных макропрепаратах. В послеоперационном периоде проводился анализ выживаемости.

Результаты

Результаты. Чувствительность метода ICG-флуоресценции составила 94,4 %, а специфичность — 83,3 %. Высокие уровни экспрессии маркеров макрофагов CD68 и CD163 статистически значимо преобладают в группе со стадией cN+ (по клинической TNM-классификации — имеются признаки поражения) (p = 0,027 и p = 0,018 соответственно). У всех пациентов с высокими уровнями CD68 и CD163 наблюдали ICG-флуоресценцию регионарных лимфатических узлов (100 %). Зарегистрировано достоверное снижение выживаемости у пациентов с высокой патоморфологической стадией T (pT по классификации TNM) (r = 0,952, p < 0,05) и получены статистически достоверные показатели выживаемости для групп pT1–pT4 (p < 0,05 для общей, опухоль-специфической и безрецидивной выживаемости (ОВ, ОСВ, БРВ соответственно)).

Обсуждение

Обсуждение. В мировой литературе появляется все больше исследований, доказывающих эффективность РАРЦ при лечении МИРМП. В сравнении с открытыми и лапароскопическими методиками демонстрируются лучшие хирургические и сопоставимые онкологические результаты.

Заключение

Заключение. Результаты анализа собственного опыта РАРЦ свидетельствуют об эффективности данного метода лечения МИРМП. Использование ICG-флуоресценции и верификации опухолевых макрофагов позволяет оказывать персонифицированную помощь пациентам онкоурологического профиля.

Introduction

Introduction. Radical cystectomy (RC) is the “gold standard” treatment for muscle-invasive bladder cancer (MIBC). Robot-assisted RC (RARC) can act as a safe and effective method of treating MIBC.

The aim of the study was to analyze our own experience with the use of RARC with intraoperative indocyanine green fluorescence (ICG) and postoperative determination of tumor macrophage levels in the treatment of patients with MIBC.

Materials and methods

Materials and methods. A study was conducted at the Clinic of the Bashkir State Medical University with the participation of 202 patients aſter RARC. 30 patients underwent intraoperative ICG fluorescence testing. The levels of tumor macrophages in the removed macropreparations were determined in all patients. In the postoperative period, a survival analysis was performed.

Results

Results. The sensitivity of the ICG fluorescence method was 94.4 %, and the specificity was 83.3 %. High levels of expression of macrophage markers CD68 and CD163 significantly predominate in the group with the cN+ stage (according to the clinical TNM classification, there are signs of damage) (p = 0.027 and p = 0.018, respectively). ICG fluorescence of regional lymph nodes (100 %) was observed in all patients with high CD68 and CD163 levels. A significant decrease in survival was recorded in patients with high pathomorphological stage T (pT according to the TNM classification) (r = 0.952, p < 0.05) and statistically significant survival rates were obtained for pT1–pT4 groups (p < 0.05 for overall, cancer-specific and recurrence-free survival (OS, CSS, RFS, respectively)).

Discussion

Discussion. More and more studies are appearing in the world literature proving the effectiveness of RARC in the treatment of patients with MIBC. Compared with open and laparoscopic techniques, better surgical and comparable oncological results are demonstrated.

Conclusion

Conclusion. The results of the analysis of the RARC’s own experience indicate the effectiveness of this method of treating MIBC. The use of ICG fluorescence and verification of tumor macrophages makesit possible to provide personalized care to oncourological patients.

мышечно-инвазивный рак мочевого пузыряробот-ассистированная радикальная цистэктомияассоциированные с опухолью макрофагииммуногистохимическая диагностикаmuscle-invasive bladder cancerrobot-assisted radical cystectomytumor-associated macrophagesimmunohistochemical diagnosisReferencesAntoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: A global overview and recent trends. European Urology. 2017;71(1):96–108. DOI: https://doi.org/10.1016/j.eururo.2016.06.010.Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: A global overview and recent trends. European Urology. 2017;71(1):96–108. DOI: https://doi.org/10.1016/j.eururo.2016.06.010.Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. (eds.). GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012 v1.0. IARC CancerBase no. 11. Lyon: International Agency for Research on Cancer; 2013. Available at: https://clck.ru/39fZS6 [Accessed 20 September 2023].Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. (eds.). GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012 v1.0. IARC CancerBase no. 11. Lyon: International Agency for Research on Cancer; 2013. Available at: https://clck.ru/39fZS6 [Accessed 20 September 2023].Wong MCS, Fung FDH, Leung C, Cheung WWL, Goggins WB, Ng CF. The global epidemiology of bladder cancer: A joinpoint regression analysis of its incidence and mortality trends and projection. Scientific Reports. 2018;8(1):1129. DOI: https://doi.org/10.1038/s41598-018-19199-z.Wong MCS, Fung FDH, Leung C, Cheung WWL, Goggins WB, Ng CF. The global epidemiology of bladder cancer: A joinpoint regression analysis of its incidence and mortality trends and projection. Scientific Reports. 2018;8(1):1129. DOI: https://doi.org/10.1038/s41598-018-19199-z.Fankhauser CD, Mostafid H. Prevention of bladder cancer incidence and recurrence: Nutrition and lifestyle. Current Opinion in Urology. 2018;28(1):88–92. DOI: https://doi.org/10.1097/MOU.0000000000000452.Fankhauser CD, Mostafid H. Prevention of bladder cancer incidence and recurrence: Nutrition and lifestyle. Current Opinion in Urology. 2018;28(1):88–92. DOI: https://doi.org/10.1097/MOU.0000000000000452.Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M, Nielsen ME, et al. Bladder cancer. Nature Reviews Disease Primers. 2017;3:17022. DOI: https://doi.org/10.1038/nrdp.2017.22.Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M, Nielsen ME, et al. Bladder cancer. Nature Reviews Disease Primers. 2017;3:17022. DOI: https://doi.org/10.1038/nrdp.2017.22.Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. European Urology. 2013;63(2):234–241. DOI: https://doi.org/10.1016/j.eururo.2012.07.033.Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. European Urology. 2013;63(2):234–241. DOI: https://doi.org/10.1016/j.eururo.2012.07.033.Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström PU, Choi W, et al. Bladder cancer. The Lancet. 2016;388(10061):2796–2810. DOI: https://doi.org/10.1016/S0140-6736(16)30512-8. Erratum in: The Lancet. 2016;388(10061):2742. DOI: https://doi.org/10.1016/S0140-6736(16)31776-7.Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström PU, Choi W, et al. Bladder cancer. The Lancet. 2016;388(10061):2796–2810. DOI: https://doi.org/10.1016/S0140-6736(16)30512-8. Erratum in: The Lancet. 2016;388(10061):2742. DOI: https://doi.org/10.1016/S0140-6736(16)31776-7.Knowles MA, Hurst CD. Molecular biology of bladder cancer: New insights into pathogenesis and clinical diversity. Nature Reviews Cancer. 2015;15(1):25–41. DOI: https://doi.org/10.1038/nrc3817.Knowles MA, Hurst CD. Molecular biology of bladder cancer: New insights into pathogenesis and clinical diversity. Nature Reviews Cancer. 2015;15(1):25–41. DOI: https://doi.org/10.1038/nrc3817.Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, et al. EAU Guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2016. European Urology. 2017;71(3):447–461. DOI: https://doi.org/10.1016/j.eururo.2016.05.041.Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, et al. EAU Guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2016. European Urology. 2017;71(3):447–461. DOI: https://doi.org/10.1016/j.eururo.2016.05.041.Oosterlinck W, Lobel B, Jakse G, Malmström PU, Stöckle M, Sternberg C; European Association of Uro logy (EAU) Working Group on Oncological Urology. Guidelines on bladder cancer. European Urology. 2002;41(2):105–112. DOI: https://doi.org/10.1016/s0302-2838(01)00026-4.Oosterlinck W, Lobel B, Jakse G, Malmström PU, Stöckle M, Sternberg C; European Association of Uro logy (EAU) Working Group on Oncological Urology. Guidelines on bladder cancer. European Urology. 2002;41(2):105–112. DOI: https://doi.org/10.1016/s0302-2838(01)00026-4.Menon M, Hemal AK, Tewari A, Shrivastava A, Shoma AM, El-Tabey NA, et al. Nerve-sparing robot-assisted radical cystoprostatectomy and urinary diversion. BJU International. 2003;92(3):232–236. DOI: https://doi.org/10.1046/j.1464-410x.2003.04329.x.Menon M, Hemal AK, Tewari A, Shrivastava A, Shoma AM, El-Tabey NA, et al. Nerve-sparing robot-assisted radical cystoprostatectomy and urinary diversion. BJU International. 2003;92(3):232–236. DOI: https://doi.org/10.1046/j.1464-410x.2003.04329.x.Tyritzis SI, Collins JW, Wiklund NP. The current status of robot-assisted cystectomy. Indian Journal of Uro logy. 2018;34(2):101–109. DOI: https://doi.org/10.4103/iju.IJU_355_17.Tyritzis SI, Collins JW, Wiklund NP. The current status of robot-assisted cystectomy. Indian Journal of Uro logy. 2018;34(2):101–109. DOI: https://doi.org/10.4103/iju.IJU_355_17.Leow JJ, Reese SW, Jiang W, Lipsitz SR, Bellmunt J, Trinh QD, et al. Propensity-matched comparison of morbidity and costs of open and robot-assisted radical cystectomies: A contemporary population-based analysis in the United States. European Urology. 2014;66(3):569–576. DOI: https://doi.org/10.1016/j.eururo.2014.01.029.Leow JJ, Reese SW, Jiang W, Lipsitz SR, Bellmunt J, Trinh QD, et al. Propensity-matched comparison of morbidity and costs of open and robot-assisted radical cystectomies: A contemporary population-based analysis in the United States. European Urology. 2014;66(3):569–576. DOI: https://doi.org/10.1016/j.eururo.2014.01.029.Bochner BH, Sjoberg DD, Laudone VP; Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group. A randomized trial of robot-assisted laparoscopic radical cystectomy. The New England Journal of Medicine. 2014;371(4):389–390. DOI: https://doi.org/10.1056/NEJMc1405213.Bochner BH, Sjoberg DD, Laudone VP; Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group. A randomized trial of robot-assisted laparoscopic radical cystectomy. The New England Journal of Medicine. 2014;371(4):389–390. DOI: https://doi.org/10.1056/NEJMc1405213.Khan MS, Gan C, Ahmed K, Ismail AF, Watkins J, Summers JA, et al. A Single-centre early phase randomised controlled three-arm trial of open, robotic, and laparoscopic radical cystectomy (CORAL). European Urology. 2016;69(4):613–621. DOI: https://doi.org/10.1016/j.eururo.2015.07.038.Khan MS, Gan C, Ahmed K, Ismail AF, Watkins J, Summers JA, et al. A Single-centre early phase randomised controlled three-arm trial of open, robotic, and laparoscopic radical cystectomy (CORAL). European Urology. 2016;69(4):613–621. DOI: https://doi.org/10.1016/j.eururo.2015.07.038.Pavlov VN, Urmantsev MF, Bakeev MR. The success of robot-assisted cystectomy in the treatment of muscle-invasive bladder cancer. Cancer Urology. 2022;18(2):123–128. (In Russ.). DOI: https://doi.org/10.17650/1726-9776-2022-18-2-123-128.Pavlov VN, Urmantsev MF, Bakeev MR. The success of robot-assisted cystectomy in the treatment of muscle-invasive bladder cancer. Cancer Urology. 2022;18(2):123–128. (In Russ.). DOI: https://doi.org/10.17650/1726-9776-2022-18-2-123-128.Tobis S, Knopf J, Silvers C, Yao J, Rashid H, Wu G, et al. Near infrared fluorescence imaging with robotic assisted laparoscopic partial nephrectomy: Initial clinical experience for renal cortical tumors. The Journal of Urology. 2011;186(1):47–52. DOI: https://doi.org/10.1016/j.juro.2011.02.2701.Tobis S, Knopf J, Silvers C, Yao J, Rashid H, Wu G, et al. Near infrared fluorescence imaging with robotic assisted laparoscopic partial nephrectomy: Initial clinical experience for renal cortical tumors. The Journal of Urology. 2011;186(1):47–52. DOI: https://doi.org/10.1016/j.juro.2011.02.2701.Siddighi S, Yune JJ, Hardesty J. Indocyanine green for intraoperative localization of ureter. American Journal of Obstetrics & Gynecology. 2014;211(4):436.e1–436.e2. DOI: https://doi.org/10.1016/j.ajog.2014.05.017.Siddighi S, Yune JJ, Hardesty J. Indocyanine green for intraoperative localization of ureter. American Journal of Obstetrics & Gynecology. 2014;211(4):436.e1–436.e2. DOI: https://doi.org/10.1016/j.ajog.2014.05.017.Kitamura T, Qian BZ, Pollard JW. Immune cell promotion of metastasis. Nature Reviews Immunology. 2015;15(2):73–86. DOI: https://doi.org/10.1038/nri3789.Kitamura T, Qian BZ, Pollard JW. Immune cell promotion of metastasis. Nature Reviews Immunology. 2015;15(2):73–86. DOI: https://doi.org/10.1038/nri3789.Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Europe PMC funders group tumor-associated macrophages as treatment targets in oncology. Nature Reviews Clinical Oncology. 2018;14:399–416. DOI: https://doi.org/10.1038/nrclinonc.2016.217.Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Europe PMC funders group tumor-associated macrophages as treatment targets in oncology. Nature Reviews Clinical Oncology. 2018;14:399–416. DOI: https://doi.org/10.1038/nrclinonc.2016.217.Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Frontiers in Immunology. 2014;5:614. DOI: https://doi.org/10.3389/fimmu.2014.00614.Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Frontiers in Immunology. 2014;5:614. DOI: https://doi.org/10.3389/fimmu.2014.00614.Feng D, Li A, Hu X, Lin T, Tang Y, Han P. Comparative effectiveness of open, laparoscopic and robot-assisted radical cystectomy for bladder cancer: A systematic review and network meta-analysis. Minerva Urology and Nephrology. 2020;72(3):251–264. DOI: https://doi.org/10.23736/S0393-2249.20.03680-2.Feng D, Li A, Hu X, Lin T, Tang Y, Han P. Comparative effectiveness of open, laparoscopic and robot-assisted radical cystectomy for bladder cancer: A systematic review and network meta-analysis. Minerva Urology and Nephrology. 2020;72(3):251–264. DOI: https://doi.org/10.23736/S0393-2249.20.03680-2.Fonseka T, Ahmed K, Froghi S, Khan SA, Dasgupta P, Shamim Khan M. Comparing robotic, laparoscopic and open cystectomy: A systematic review and meta-analysis. Archivio Italiano Di Urologia E Andrologia. 2015;87(1):41–48. DOI: https://doi.org/10.4081/aiua.2015.1.41.Fonseka T, Ahmed K, Froghi S, Khan SA, Dasgupta P, Shamim Khan M. Comparing robotic, laparoscopic and open cystectomy: A systematic review and meta-analysis. Archivio Italiano Di Urologia E Andrologia. 2015;87(1):41–48. DOI: https://doi.org/10.4081/aiua.2015.1.41.Han JH, Ku JH. Robot-assisted radical cystectomy: Where we are in 2023. Investigative and Clinical Urology. 2023;64(2):107–117. DOI: https://doi.org/10.4111/icu.20220384.Han JH, Ku JH. Robot-assisted radical cystectomy: Where we are in 2023. Investigative and Clinical Urology. 2023;64(2):107–117. DOI: https://doi.org/10.4111/icu.20220384.Catto JWF, Khetrapal P, Ricciardi F, Ambler G, Williams NR, Al-Hammouri T, et al; iROC Study Team. Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: A randomized clinical trial. JAMA. 2022;327(21):2092–2103. DOI: https://doi.org/10.1001/jama.2022.7393.Catto JWF, Khetrapal P, Ricciardi F, Ambler G, Williams NR, Al-Hammouri T, et al; iROC Study Team. Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: A randomized clinical trial. JAMA. 2022;327(21):2092–2103. DOI: https://doi.org/10.1001/jama.2022.7393.Rai BP, Bondad J, Vasdev N, Adshead J, Lane T, Ahmed K, et al. Robotic versus open radical cystectomy for bladder cancer in adults. Cochrane Database of Systematic Reviews. 2019;4(4):CD011903. DOI: https://doi.org/10.1002/14651858.CD011903.pub2.Rai BP, Bondad J, Vasdev N, Adshead J, Lane T, Ahmed K, et al. Robotic versus open radical cystectomy for bladder cancer in adults. Cochrane Database of Systematic Reviews. 2019;4(4):CD011903. DOI: https://doi.org/10.1002/14651858.CD011903.pub2.Mortezavi A, Crippa A, Kotopouli MI, Akre O, Wiklund P, Hosseini A. Association of open vs robot-assisted radical cystectomy with mortality and perioperative outcomes among patients with bladder cancer in Sweden. JAMA Network Open. 2022;5(4):e228959. DOI: https://doi.org/10.1001/jamanetworkopen.2022.8959.Mortezavi A, Crippa A, Kotopouli MI, Akre O, Wiklund P, Hosseini A. Association of open vs robot-assisted radical cystectomy with mortality and perioperative outcomes among patients with bladder cancer in Sweden. JAMA Network Open. 2022;5(4):e228959. DOI: https://doi.org/10.1001/jamanetworkopen.2022.8959.Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–455. DOI: https://doi.org/10.1038/nature12034.Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–455. DOI: https://doi.org/10.1038/nature12034.Fu H, Zhu Y, Wang Y, Liu Z, Zhang J, Xie H, et al. Identification and validation of stromal immunotype predict survival and benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer. Clinical Cancer Research. 2018;24:3069–3078. DOI: https://doi.org/10.1158/1078-0432.CCR-17-2687.Fu H, Zhu Y, Wang Y, Liu Z, Zhang J, Xie H, et al. Identification and validation of stromal immunotype predict survival and benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer. Clinical Cancer Research. 2018;24:3069–3078. DOI: https://doi.org/10.1158/1078-0432.CCR-17-2687.Boström MM, Irjala H, Mirtti T, Taimen P, Kauko T, Ålgars A, et al. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS ONE. 2015;10: e0133552. DOI: https://doi.org/10.1371/journal.pone.0133552.Boström MM, Irjala H, Mirtti T, Taimen P, Kauko T, Ålgars A, et al. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS ONE. 2015;10: e0133552. DOI: https://doi.org/10.1371/journal.pone.0133552.Huang CP, Liu LX, Shyr CR. Tumor-associated macrophages facilitate bladder cancer progression by increasing cell growth, migration, invasion and cytokine expression. Anticancer Research. 2020;40:2715–2724. DOI: https://doi.org/10.21873/anticanres.14243.Huang CP, Liu LX, Shyr CR. Tumor-associated macrophages facilitate bladder cancer progression by increasing cell growth, migration, invasion and cytokine expression. Anticancer Research. 2020;40:2715–2724. DOI: https://doi.org/10.21873/anticanres.14243.

The authors declare that there are no conflicts of interest present.