Compared Efficacy of Adjuvant Intravesical BCG-TICE Vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis

Background: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet.

Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan-Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed.

Results: 852 Ta-T1 NMIBCs ( = 719, 84.4% on TICE; = 133, 15.6% on RIVM) with a median of 53 (24-77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan-Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, = 0.008; HR: 0.45 95% CI 0.25-0.81).

Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

Citing Articles

Advancements in the Diagnosis, Treatment, and Risk Stratification of Non-Muscle Invasive Bladder Cancer.

Smani S, DuBois J, Zhao K, Sutherland R, Rahman S, Humphrey P Curr Oncol Rep. 2025; .

PMID: 39976835 DOI: 10.1007/s11912-025-01645-7.

Oncological outcomes and prognostic implications of T1 histo-anatomic substaging in the management of high-Grade non-muscle invasive bladder cancer: results from a large single centre series.

Finati M, Fanelli A, Cinelli F, Schiavone N, Falagario U, Ricapito A World J Urol. 2024; 43(1):47.

PMID: 39724414 DOI: 10.1007/s00345-024-05410-6.

Carcinoma In Situ (CIS): Is There a Difference in Efficacy between Various BCG Strains? A Comprehensive Review of the Literature.

Llano A, Chan A, Kuk C, Kassouf W, Zlotta A Cancers (Basel). 2024; 16(2).

PMID: 38254736 PMC: 10813486. DOI: 10.3390/cancers16020245.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Huang L, Lin Y, Chuang H, Chuang C, Pang S, Wu C Front Oncol. 2023; 13:1180888.

PMID: 37637042 PMC: 10448957. DOI: 10.3389/fonc.2023.1180888.

Intravesical BCG in bladder cancer induces innate immune responses against SARS-CoV-2.

Pichler R, Diem G, Hackl H, Koutnik J, Mertens L, D Andrea D Front Immunol. 2023; 14:1202157.

PMID: 37520557 PMC: 10374029. DOI: 10.3389/fimmu.2023.1202157.

References

Gontero P, Sylvester R, Pisano F, Joniau S, Vander Eeckt K, Serretta V . Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients. Eur Urol. 2014; 67(1):74-82. DOI: 10.1016/j.eururo.2014.06.040. View

Sengiku A, Ito M, Miyazaki Y, Sawazaki H, Takahashi T, Ogura K . A prospective comparative study of intravesical bacillus Calmette-Guérin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer. J Urol. 2013; 190(1):50-4. DOI: 10.1016/j.juro.2013.01.084. View

Babjuk M, Burger M, Capoun O, Cohen D, Comperat E, Dominguez Escrig J . European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol. 2021; 81(1):75-94. DOI: 10.1016/j.eururo.2021.08.010. View

Witjes J, Dalbagni G, Karnes R, Shariat S, Joniau S, Palou J . The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer. Urol Oncol. 2016; 34(11):484.e19-484.e25. PMC: 5515280. DOI: 10.1016/j.urolonc.2016.05.033. View

Sylvester R, van der Meijden A, Lamm D . Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002; 168(5):1964-70. DOI: 10.1016/S0022-5347(05)64273-5. View

Miyake M, Tatsumi Y, Matsumoto H, Nagao K, Matsuyama H, Inamoto T . Outcomes of subsequent non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin after radical nephroureterectomy for upper urinary tract urothelial carcinoma. BJU Int. 2017; 121(5):764-773. DOI: 10.1111/bju.14111. View

Boehm B, Cornell J, Wang H, Mukherjee N, Oppenheimer J, Svatek R . Efficacy of bacillus Calmette-Guérin Strains for Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Network Meta-Analysis. J Urol. 2017; 198(3):503-510. PMC: 6464123. DOI: 10.1016/j.juro.2017.01.086. View

Lamm D . Efficacy and safety of bacille Calmette-Guérin immunotherapy in superficial bladder cancer. Clin Infect Dis. 2000; 31 Suppl 3:S86-90. DOI: 10.1086/314064. View

Cernuschi T, Malvolti S, Nickels E, Friede M . Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance. Vaccine. 2017; 36(4):498-506. PMC: 5777639. DOI: 10.1016/j.vaccine.2017.12.010. View

10.

Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G . Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin 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.... Eur Urol. 2012; 63(3):462-72. DOI: 10.1016/j.eururo.2012.10.039. View

11.

Unda-Urzaiz M, Cozar-Olmos J, Minana-Lopez B, Camarero-Jimenez J, Brugarolas-Rossello X, Zubiaur-Libano C . Safety and efficacy of various strains of bacille Calmette-Guérin in the treatment of bladder tumours in standard clinical practice. Actas Urol Esp (Engl Ed). 2018; 42(4):238-248. DOI: 10.1016/j.acuro.2017.10.003. View

12.

Grimm M, van der Heijden A, Colombel M, Muilwijk T, Martinez-Pineiro L, Babjuk M . 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.... Eur Urol. 2020; 78(5):690-698. DOI: 10.1016/j.eururo.2020.04.066. View

13.

Krajewski W, Matuszewski M, Poletajew S, Grzegrzolka J, Zdrojowy R, Kolodziej A . Are There Differences in Toxicity and Efficacy between Various Bacillus Calmette-Guerin Strains in Bladder Cancer Patients? Analysis of 844 Patients. Urol Int. 2018; 101(3):277-284. DOI: 10.1159/000492722. View

14.

Rentsch C, Birkhauser F, Biot C, Gsponer J, Bisiaux A, Wetterauer C . Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy. Eur Urol. 2014; 66(4):677-88. DOI: 10.1016/j.eururo.2014.02.061. View

15.

DAndrea D, Soria F, Abufaraj M, Pones M, Gontero P, Machado A . Comparative Effectiveness of Intravesical BCG-Tice and BCG-Moreau in Patients With Non-muscle-invasive Bladder Cancer. Clin Genitourin Cancer. 2019; 18(1):20-25.e2. DOI: 10.1016/j.clgc.2019.10.021. View

16.

Huang Z, Liu H, Wang Y, Zhang C, Xu T . Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis. Curr Med Res Opin. 2017; 33(8):1379-1387. DOI: 10.1080/03007995.2017.1326889. View

17.

Del Giudice F, Busetto G, Gross M, Maggi M, Sciarra A, Salciccia S . Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis. J Cancer Res Clin Oncol. 2021; 147(10):3073-3080. PMC: 8397662. DOI: 10.1007/s00432-021-03571-0. View

18.

Nowak L, Krajewski W, Moschini M, Chorbinska J, Poletajew S, Tukiendorf A . Assessment of the oncological outcomes of three different bacillus Calmette-Guérin strains in patients with high-grade T1 non-muscle-invasive bladder cancer. Arab J Urol. 2021; 19(1):78-85. PMC: 7954505. DOI: 10.1080/2090598X.2021.1874628. View

19.

van Puffelen J, Keating S, Oosterwijk E, van der Heijden A, Netea M, Joosten L . Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nat Rev Urol. 2020; 17(9):513-525. DOI: 10.1038/s41585-020-0346-4. View

20.

Bohle A, Bock P . Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology. 2004; 63(4):682-6. DOI: 10.1016/j.urology.2003.11.049. View