POSSIBILITIES OF ADJUVANT INTRAVESICAL DRUG THERAPY IN NONINVASIVE MUSCULAR BLADDER CANCER (LITERATURE REVIEW)
DOI:
https://doi.org/10.54890/1694-8882-2025-1-187Abstract
Noninvasive musculoskeletal bladder cancer remains one of the most common diseases in the structure of oncourological diseases, ranking 7th in the world. According to statistics, the number of detected cases is increasing every year. In 75% of cases, according to the literature, this is noninvasive muscular bladder cancer. Timely diagnosis makes it possible to avoid minimally invasive treatment methods, such as transurethral resection or planar resection with mandatory further adjuvant intravesical drug therapy. Currently, the following types are used: Mitomycin C, Doxorubicin, BCG therapy, the most effective of which is BCG therapy, followed by Mitomycin C and Doxorubicin. Also, some authors note the high effectiveness of intravesical chemotherapy in combination with local hyperthermia. Given the acute deficiency of BCG, Mitomycin C, the only available cytostatic agent is Doxorubicin. An alternative is to conduct intravesical chemotherapy with Cisplatin and Gemcitabine, which have long been used for invasive bladder cancer. However, further research is required to confirm the effectiveness of these drugs in non-invasive muscular bladder cancer. Thus, these medicines can serve as an alternative in an era of shortage of recommended drugs.
Keywords:
bladder cancer, non-invasive muscle bladder cancer, intravesical chemotherapy, gemcitabine, cisplatin, hyperthermia, transurethral resection of the bladder.References
1. Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol. 2022;81(1):75-94. https://doi.org/10.1016/j.eururo.2021.08.010
2. Токтомушев Т.К., Эшалиев Т.К., Ибраев Б.М., Саякова А.У., Керимов А.Д., Токтомушева А.А., Икбал М.В. Рак мочевого пузыря в Кыргызской Республике. Московский хирургический журнал. 2018;2:62-64. https://doi.org/10.17238/issn2072-3180.2018.2.62-64
3. Иванов С.А., Заборский И.Н., Чайков В.С. Лечение немышечно-инвазивного рака мочевого пузыря высокого риска. Вестник урологии. 2017;5(2):42 49. https://doi.org/10.21886/2308-6424-2017-5-2-42-49
4. Compérat E, Larré S, Roupret M, Neuzillet Y, Pignot G, Quintens H, et al. Clinicopathological characteristics of urothelial bladder cancer in patients less than 40 years old. Virchows Arch. 2015;466(5):589-594. https://doi.org/10.1007/s00428-015-1739-2
5. Otto W, Breyer J, Herdegen S, Eder F, Bertz S, May M, et al. WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach. Int Urol Nephrol. 2017;49(3):431-437. https://doi.org/10.1007/s11255-016-1491-9
6. Cimadamore A, Lopez-Beltran A, Scarpelli M, Cheng L, Montironi R. Re: Bas W.G. van Rhijn, Anouk E. Hentschel, Johannes Bründl, et al. Prognostic Value of the WHO1973 and WHO2004/2016 Classification Systems for Grade in Primary Ta/T1 Non-muscle-invasive Bladder Cancer: A Multicenter European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel Study. Eur Urol Oncol 2021;4(4):182-191: Image Analysis, Nuclear Abnormality Index, and Pattern Recognition Analysis. Eur Urol Oncol. 2021;4(4):671-673. https://doi.org/10.1016/j.euo.2021.06.002
7. Hentschel AE, van Rhijn BWG, Bründl J, Compérat EM, Plass K, Rodríguez O, et al. Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019? Urol Oncol. 2020;38(5):440-448. https://doi.org/10.1016/j.urolonc. 2019.10.002
8. Soria F, Droller MJ, Lotan Y, Gontero, P., D'Andrea D, Gust KM, et al. An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer. World J Urol. 2018;36(12):1981-1995. https://doi.org/10.1007/s00345-018-2380-x
9. Sylvester RJ, Oosterlinck W, Witjes JA. The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol. 2008;53(4):709-719. https://doi.org/10.1016/j.eururo.2008.01.015
10. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-241. https://doi.org/10.1016/ j.eururo.2012.07.033
11. Teoh JY, MacLennan S, Chan VW, Miki J, Lee HY, Chiong E, et al. An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey, and a Consensus Meeting. Eur Urol. 2020;78(4):546-569. https://doi.org/10.1016/j.eururo. 2020.04.059
12. Gallioli A, Diana P, Fontana M, Territo A, Rodriguez-Faba Ó, Gaya JM, et al. En Bloc Versus Conventional Transurethral Resection of Bladder Tumors: A Single-center Prospective Randomized Noninferiority Trial. Eur Urol Oncol. 2022;5(4):440-448. https://doi.org/10.1016/j.euo.2022.05.001
13. D'Andrea D, Soria F, Hurle R, Enikeev D, Kotov S, Régnier S, et al. En Bloc Versus Conventional Resection of Primary Bladder Tumor (eBLOC): A Prospective, Multicenter, Open-label, Phase 3 Randomized Controlled Trial. Eur Urol Oncol. 2023;6(5):508-515. https://doi.org/10.1016/j.euo.2023.07.010
14. Yanagisawa T, Mori K, Motlagh RS, Kawada T, Mostafaei H, Quhal F, et al. En Bloc Resection for Bladder Tumors: An Updated Systematic Review and Meta-Analysis of Its Differential Effect on Safety, Recurrence and Histopathology. J Urol. 2022;207(4):754-768. https://doi.org/10.1097/JU.0000000000002444
15. Li Z, Zhou Z, Cui Y, Zhang Y. Systematic review and meta-analysis of randomized controlled trials of perioperative outcomes and prognosis of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer. Int J Surg. 2022;104:106777. https://doi.org/10.1016/j.ijsu.2022.106777
16. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180-183. https://doi.org/10.1016/s0022-5347(17)58737-6
17. Soloway MS, Masters S. Urothelial susceptibility to tumor cell implantation: influence of cauterization. Cancer. 1980;46(5):1158-1163. https://doi.org/ 10.1002/1097-0142(19800901)46:5<1158::aid cncr2820460514>3.0.co;2-e
18. Pode D, Alon Y, Horowitz AT, Vlodavsky I, Biran S. The mechanism of human bladder tumor implantation in an in vitro model. J Urol. 1986;136(2):482-486. https://doi.org/10.1016/s0022-5347(17)44926-3
19. Böhle A, Jurczok A, Ardelt P, Wulf T, Ulmer AJ, Jocham D, et al. Inhibition of bladder carcinoma cell adhesion by oligopeptide combinations in vitro and in vivo. J Urol. 2002;167(1):357-363. PMID: 11743356
20. Sylvester RJ, Oosterlinck W, Holmang S, Sydes MR, Birtle A, Gudjonsson S, et al. Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. 2016;69(2):231-244. https://doi.org/10.1016/j.eururo. 2015.05.050
21. Perlis N, Zlotta AR, Beyene J, Finelli A, Fleshner NE, Kulkarni GS. Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. Eur Urol. 2013;64(3):421-430. https://doi.org/10.1016/j.eururo.2013.06.009
22. Kondás J, Kiss L, Határ A, Kiss A, Lukács T, Szeldeli P, et al. The effect of intravesical mitomycin C on the recurrence of superficial (Ta-T1) bladder cancer. A Hungarian Multicenter Study. Int Urol Nephrol. 1999;31(4):451-456. https://doi.org/ 10.1023/a:1007155026151
23. Tabayoyong WB, Kamat AM, O'Donnell MA, McKiernan JM, Ray-Zack MD, Palou J, et al. Systematic Review on the Utilization of Maintenance Intravesical Chemotherapy in the Management of Non-muscle-invasive Bladder Cancer. Eur Urol Focus. 2018;4(4):512-521. https://doi.org/10.1016/j.euf.2018.08.019
24. Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009;56(2):247-256. https://doi.org/10.1016/j.eururo.2009.04.038
25. Akaza H, Isaka S, Koiso K, Kotake T, Machida T, Maru A, et al. Comparative analysis of short-term and long-term prophylactic intravesical chemotherapy of superficial bladder cancer. Prospective, randomized, controlled studies of the Japanese Urological Cancer Research Group. Cancer Chemother Pharmacol. 1987;20 Suppl:S91-S96. https://doi.org/10.1007 /BF00262495
26. Русаков И.Г., Быстров А.А., Хирургическое лечение, химио- и иммунотерапия больных поверхностным раком мочевого пузыря. Практическая онкология. 2003;4(4):214-224.
27. Schmidt S, Kunath F, Coles B, Draeger DL, Krabbe LM, Dersch R, et al. Intravesical Bacillus Calmette-Guérin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev. 2020;1(1):CD011935. https://doi.org/10.1002/ 14651858.CD011935.pub2
28. van der Meijden AP, Sylvester RJ, Oosterlinck W, Hoeltl W, Bono AV; EORTC Genito-Urinary Tract Cancer Group. Maintenance Bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. Eur Urol. 2003;44(4):429-434. https://doi.org/10.1016/s0302-2838(03)00357-9
29. Jue JS, Alameddine M, González J, Ciancio G. Risk factors, management, and survival of bladder cancer after kidney transplantation. Actas Urol Esp (Engl Ed). 2021;45(6):427-438. https://doi.org/10.1016/j.acuroe.2020.09.009
30. Grimm MO, Caris C, Witjes WPJ; NIMBUS study group. Reply to Emre Karabay and İlker Tınay's Letter to the Editor re: Treatment of High-grade Non-muscle-invasive Bladder Carcinoma by Standard Number and Dose of BCG Instillations Versus Reduced Number and Standard Dose of BCG Instillations: Results of the European Association of Urology Research Foundation Randomised Phase III Clinical Trial "NIMBUS". Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.04.066. Eur Urol. 2020;78(4):e163-e164. https://doi.org/10.1016/j.eururo.2020.07.004
31. Solsona E, Madero R, Chantada V, Fernandez JM, Zabala JA, Portillo JA, et al. Sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive bladder cancer in intermediate- and high-risk patients: final outcome of CUETO 93009, a randomized prospective trial. Eur Urol. 2015;67(3):508-516. https://doi.org/10.1016/j.eururo.2014.09.026
32. Steinberg RL, Thomas LJ, Brooks N, Mott SL, Vitale A, Crump T, et al. Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer. J Urol. 2020;203(5):902-909. https://doi.org/10.1097/JU.0000000000000688
33. McElree IM, Packiam VT, Steinberg RL, Mott SL, Gellhaus PT, Nepple KG, et al. Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non-Muscle-Invasive Bladder Cancer. J Urol. 2022;208(5):969-977. https://doi.org/10.1097/JU.0000000000002848
34. Angulo JC, Álvarez-Ossorio JL, Domínguez-Escrig JL, Moyano JL, Sousa A, Fernández JM, et al. Hyperthermic Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: Results of the HIVEC-1 Trial. Eur Urol Oncol. 2023;6(1):58-66. https://doi.org/10.1016/j.euo.2022.10.008
35. Takenaka A, Yamada Y, Miyake H, Hara I, Fujisawa M. Clinical outcomes of bacillus Calmette-Guérin instillation therapy for carcinoma in situ of urinary bladder. Int J Urol. 2008;15(4):309-313. https://doi.org/10.1111/j.1442-2042.2008.02012.x
36. Lamm DL. Carcinoma in situ. Urol Clin North Am. 1992;19(3):499-508.
37. Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP, et al. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA. 2018;319(18): 1880-1888. https://doi.org/10.1001/ jama.2018.4657
38. Delto JC, Kobayashi T, Benson M, McKiernan J, Abate-Shen C. Preclinical analyses of intravesical chemotherapy for prevention of bladder cancer progression. Oncotarget. 2013;4(2):269-276. https://doi.org/10.18632/oncotarget.852
39. Gontero P, Casetta G, Maso G, Sogni F, Pretti G, Zitella A, et al. Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC). Eur Urol. 2004;46(3):339-343. https://doi.org/10.1016/j.eururo.2004.05.001
40. Серегин И.В., Самойленко В.М., Фигурин К.М. Внутрипузырное применение гемцитабина у больных поверхностным раком мочевого пузыря, резистентным к внутрипузырной иммунотерапии вакциной БЦЖ. Онкоурология 2005;2:32-4.
41. Садкова Ю.А., Гришина М.Г., Пигаев С.Е., Федорос Е.И. Перспективы использования платиновых препаратов. Медико-фармацевтический журнал ПУЛЬС. 2023;25(12):43-50. https://doi.org/10.26787/nydha-2686-6838-2023-25-12-43-50
42. Зырьянов Б.Н., Селиванов С.П. Проницаемость стенки мочевого пузыря для цисплатина при местном применении. Урология. 2000;5:28-30.
Downloads
Published
How to Cite
Issue
Section
