AccScience Publishing / Bladder / Online First / DOI: 10.14440/bladder.2024.0051
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RESEARCH ARTICLE

Tolerability and efficacy of induction Bacillus Calmette–Guérin for non-muscle invasive bladder cancer

Mann Patel1† ,  Aravind Rajagopalan1† ,  Ellen M. Cahill1,2 ,  Kevin J. Chua3 ,  Rachel Passarelli3 ,  John Pfail3 ,  Sai Krishnaraya Doppalapudi3 ,  David Golombos3 ,  Thomas Jang3 ,  Vignesh T. Packiam3 ,  Saum Ghodoussipour3*
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1 Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, United States
2 Department of Urology, School of Medicine, Yale University, New Haven, Connecticut 06510, United States
3 Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson University Hospital, New Brunswick, New Jersey 08901, United States
Bladder, e21200031 https://doi.org/10.14440/bladder.2024.0051
Submitted: 31 October 2024 | Revised: 6 December 2024 | Accepted: 24 December 2024 | Published: 11 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: Intravesical Bacillus Calmette–Guérin (BCG) is the standard treatment for intermediate-risk, high-grade, and high-risk non-muscle invasive bladder cancer (NMIBC). However, it is associated with adverse effects, potentially causing treatment interruptions or discontinuation. Objectives: This study analyzed the tolerability and efficacy of induction BCG, with associated patient- and disease-related factors. Methods: A retrospective analysis was conducted on BCG-naive patients diagnosed with high-grade NMIBC, who received induction BCG at our institution between 2011 and 2021. Tolerability was defined as the completion of a 6-week induction course of BCG without treatment interruption or discontinuation. Multivariable logistic regression was performed to determine risk factors associated with the inability to tolerate treatment. Results: Induction BCG was given to 203 NMIBC patients, where 147 (72%) patients tolerated the treatment. Treatment interruptions occurred in 44 (22%) patients, while 12 (5.9%) patients discontinued the treatment. The median length of interruption was 1 week, primarily due to concerns about urinary tract infection (UTI) (n = 18, 41%) or gross hematuria (n = 5, 11%). No significant difference in 1-year recurrence rates was observed between those who tolerated BCG and those who did not (50% vs. 48%). Risk factors associated with the inability to tolerate induction BCG included male sex (odds ratio [OR] = 5.76, p < 0.01), hypertension (OR = 3.47, p = 0.02), and low pre-treatment hemoglobin levels (OR = 0.73, p = 0.03). Conclusion: Inability to tolerate BCG occurred in 28% of patients, with 5.9% experiencing discontinuation. Interruptions were short, mostly concerning UTI, and rarely leading to discontinuation. Poor tolerability was associated with male sex, hypertension, and low pre-treatment hemoglobin levels, highlighting critical targets for reducing the risk of BCG interruption or discontinuation.

Keywords
Bacillus Calmette–Guérin
Adverse effects
Tolerability
Non-muscle-invasive bladder cancer
Funding
This work is supported by a grant from the National Cancer Institute (P30CA072720).
Conflict of interest
Dr. Ghoudoussipour is a consultant for UroGen and Janssen, while Dr. Packiam is a consultant for Valar Labs, Veracyte, and Guidepoint. The author(s) have no other potential conflicts of interest concerning the research, authorship, and/ or publication of this article
References
  1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi: 10.3322/caac.21820

 

  1. Sylvester RJ. Bacillus Calmette-Guerin treatment of non-muscle invasive bladder cancer. Int J Urol. 2011;18(2):113-120. doi: 10.1111/j.1442-2042.2010.02678.x

 

  1. Holzbeierlein JM, Bixler BR, Buckley DI, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline: 2024 amendment. J Urol. 2024;211(4):533-538. doi: 10.1097/JU.0000000000003846

 

  1. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021-1029. doi: 10.1016/j.juro.2016.06.049

 

  1. Power NE, Izawa J. Comparison of guidelines on non-muscle invasive bladder cancer (EAU, CUA, AUA, NCCN, NICE). Bladder Cancer. 2016;2(1):27-36. doi: 10.3233/BLC-150034

 

  1. Nummi A, Jarvinen R, Sairanen J, Huotari K. A retrospective study on tolerability and complications of bacillus Calmette- Guerin (BCG) instillations for non-muscle-invasive bladder cancer. Scand J Urol. 2019;53(2-3):116-122. doi: 10.1080/21681805.2019.1609080

 

  1. Ferro M, Tataru OS, Musi G, et al. Modified glasgow prognostic score as a predictor of recurrence in patients with high grade non-muscle invasive bladder cancer undergoing intravesical bacillus calmette-guerin immunotherapy. Diagnostics (Basel). 2022;12(3):586. doi: 10.3390/diagnostics12030586

 

  1. Matulay JT, Li R, Hensley PJ, et al. Contemporary outcomes of patients with nonmuscle-invasive bladder cancer treated with bacillus Calmette-Guerin: Implications for clinical trial design. J Urol. 2021;205(6):1612-1621. doi: 10.1097/JU.0000000000001633

 

  1. Daniels MJ, Barry E, Schoenberg M, et al. Contemporary oncologic outcomes of second induction course BCG in patients with nonmuscle invasive bladder cancer. Urol Oncol. 2020;38(1):5e9-5e16. doi: 10.1016/j.urolonc.2019.05.018

 

  1. Subiela JD, Rodriguez Faba O, Guerrero Ramos F, et al. Carcinoma in situ of the urinary bladder: A systematic review of current knowledge regarding detection, treatment, and outcomes. Eur Urol Focus. 2020;6(4):674-682. doi: 10.1016/j.euf.2019.03.012

 

  1. Brausi M, Oddens J, Sylvester R, et al. Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate-and high-risk Ta, T1 papillary carcinoma of the bladder: Results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol. 2014;65(1):69-76. doi: 10.1016/j.eururo.2013.07.021

 

  1. Kamat AM, Li R, O’Donnell MA, et al. Predicting response to intravesical bacillus Calmette-Guerin immunotherapy: Are we there yet? A systematic review. Eur Urol. 2018;73(5):738-748. doi: 10.1016/j.eururo.2017.10.003

 

  1. Contieri R, Hurle R, Paciotti M, et al. Accuracy of the European Association of Urology (EAU) NMIBC 2021 scoring model in predicting progression in a large cohort of HG T1 NMIBC patients treated with BCG. Minerva Urol Nephrol. 2023;75(2):180-187. doi: 10.23736/S2724-6051.22.04953-9

 

  1. Farah NB, Ghanem R, Amr M. Treatment efficacy and tolerability of intravesical bacillus Calmette-Guerin (BCG)- RIVM strain: Induction and maintenance protocol in high grade and recurrent low grade non-muscle invasive bladder cancer (NMIBC). BMC Urol. 2014;14:11. doi: 10.1186/1471-2490-14-11

 

  1. Zlotta AR, Fleshner NE, Jewett MA. The management of BCG failure in non-muscle-invasive bladder cancer: An update. Can Urol Assoc J. 2009;3(6 Suppl 4):S199-S205. doi: 10.5489/cuaj.1196

 

  1. Joshua JM, Vijayan M, Pooleri GK. A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer. Ther Adv Urol. 2019;11:1756287219833056. doi: 10.1177/1756287219833056

 

  1. Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: One-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013;63(3):462-472. doi: 10.1016/j.eururo.2012.10.039

 

  1. Koch GE, Smelser WW, Chang SS. Side effects of intravesical BCG and chemotherapy for bladder cancer: What they are and how to manage them. Urology. 2021;149:11-20. doi: 10.1016/j.urology.2020.10.039

 

  1. Decaestecker K, Oosterlinck W. Managing the adverse events of intravesical bacillus Calmette-Guerin therapy. Res Rep Urol. 2015;7:157-63. doi: 10.2147/RRU.S63448

 

  1. Martinez-Pineiro JA, Martinez-Pineiro L, Solsona E, et al. Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial. J Urol. 2005;174(4 Pt 1):1242-1247. doi: 10.1097/01.ju.0000173919.28835.aa

 

  1. Zeng S, Yu X, Ma C, et al. Low-dose versus standard dose of bacillus Calmette-Guerin in the treatment of nonmuscle invasive bladder cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2015;94(49):e2176. doi: 10.1097/MD.0000000000002176

 

  1. Fadel J, Simonyan D, Fradet V, et al. Analysis of sex-based differences to Bacillus Calmette-Guerin for non-muscle invasive bladder cancer. Urol Oncol. 2022;40(12):539.e1-539.e8. doi: 10.1016/j.urolonc.2022.09.024

 

  1. Dobruch J, Daneshmand S, Fisch M, et al. Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes. Eur Urol. 2016;69(2):300-310. doi: 10.1016/j.eururo.2015.08.037

 

  1. Kluth LA, Fajkovic H, Xylinas E, et al. Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder. World J Urol. 2013;31(5):1029-1036. doi: 10.1007/s00345-012-0996-9

 

  1. Boorjian SA, Zhu F, Herr HW. The effect of gender on response to bacillus Calmette-Guerin therapy for patients with non-muscle-invasive urothelial carcinoma of the bladder. BJU Int. 2010;106(3):357-361. doi: 10.1111/j.1464-410X.2009.09137.x

 

  1. Mungan NA, Kiemeney LA, van Dijck JA, van der Poel HG, Witjes JA. Gender differences in stage distribution of bladder cancer. Urology. 2000;55(3):368-371. doi: 10.1016/s0090-4295(99)00481-1

 

  1. Rubi H, Mudey G, Kunjalwar R. Catheter-associated urinary tract infection (CAUTI). Cureus. 2022;14(10):e30385. doi: 10.7759/cureus.30385

 

  1. Sklar DP, Diven B, Jones J. Incidence and magnitude of catheter-induced hematuria. Am J Emerg Med. 1986;4(1):14-16. doi: 10.1016/0735-6757(86)90242-1

 

  1. Zhang Y. Understanding the gender disparity in bladder cancer risk: the impact of sex hormones and liver on bladder susceptibility to carcinogens. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2013;31(4):287-304. doi: 10.1080/10590501.2013.844755

 

  1. Mitra AP, Skinner EC, Schuckman AK, Quinn DI, Dorff TB, Daneshmand S. Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: A critical analysis of 1,994 patients. Urol Oncol. 2014;32(1):52.e1-9. doi: 10.1016/j.urolonc.2013.08.007

 

  1. Dal Moro F, Bovo A, Crestani A, Vettor R, Gardiman MP, Zattoni F. Effect of hypertension on outcomes of high-risk patients after BCG-treated bladder cancer: A single-institution long follow-up cohort study. Medicine (Baltimore). 2015;94(9):e589. doi: 10.1097/MD.0000000000000589

 

  1. Kok VC, Zhang HW, Lin CT, Huang SC, Wu MF. Positive association between hypertension and urinary bladder cancer: Epidemiologic evidence involving 79,236 propensity score-matched individuals. Ups J Med Sci. 2018;123(2):109-115. doi: 10.1080/03009734.2018.1473534

 

  1. Teleka S, Hindy G, Drake I, et al. Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. PLoS One. 2020;15(11):e0241711. doi: 10.1371/journal.pone.0241711

 

  1. Ahmadinezhad M, Arshadi M, Hesari E, Sharafoddin M, Azizi H, Khodamoradi F. The relationship between metabolic syndrome and its components with bladder cancer: A systematic review and meta-analysis of cohort studies. Epidemiol Health. 2022;44:e2022050. doi: 10.4178/epih.e2022050

 

  1. Li YM, Xu JH, Zhao YX. Predictors of urinary tract infection in acute stroke patients: A cohort study. Medicine (Baltimore). 2020;99(27):e20952. doi: 10.1097/MD.0000000000020952

 

  1. Madeddu C, Gramignano G, Astara G, et al. Pathogenesis and treatment options of cancer related anemia: Perspective for a targeted mechanism-based approach. Front Physiol. 2018;9:1294. doi: 10.3389/fphys.2018.01294

 

  1. Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer. Can Urol Assoc J. 2010;4(1):56-64. doi: 10.5489/cuaj.777

 

  1. Lee S, Lim B, You D, et al. Association of Bacillus Calmette- Guerin shortages with bladder cancer recurrence: A single-center retrospective study. Urol Oncol. 2020;38(11):851.e11- 851.e17. doi: 10.1016/j.urolonc.2020.07.014

 

  1. Lobo N, Bree KK, Hensley PJ, et al. Reduced-dose bacillus Calmette-Guerin (BCG) in an era of BCG shortage: Real-world experience from a tertiary cancer centre. BJU Int. 2022;130(3):323-330. doi: 10.1111/bju.15661

 

  1. Chun B, He M, Jones C, et al. Variation in statewide intravesical treatment rates for non-muscle invasive bladder cancer during the Bacillus Calmette-Guerin drug shortage. Urology. 2023;177:74-80. doi: 10.1016/j.urology.2023.02.044
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Bladder, Electronic ISSN: 2327-2120 Print ISSN: TBA, Published by POL Scientific
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