BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. PATIENT SUMMARY: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.

Department of Surgical Science John Radcliffe Hospital University of Oxford Oxford UK

Department of Surgical Sciences Molinette Hospital University of Studies of Turin Turin Italy

Department of Surgical Sciences Uppsala University Uppsala Sweden

Department of Urology Centre Hospitalier Universitaire La Milétrie University of Poitiers Poitiers France

Department of Urology Comprehensive Cancer Center Medical University Vienna Vienna Austria

Department of Urology Fundacio Puigvert University of Barcelona Barcelona Spain

Department of Urology Mayo Clinic Rochester MN

Department of Urology Motol Hospital 2nd Faculty of Medicine Charles University of Prague Prague Czech Republic

Department of Urology Paolo Giaccone General Hospital Palermo Italy

Department of Urology RadboudUMC Nijmegen The Netherlands

Department of Urology Santa Chiara Hospital Trento Italy

Department of Urology Sismanoglio Hospital University of Athens Athens Greece

Department of Urology Spanish National Cancer Research Centre Madrid Madrid Spain

Department of Urology University Hospital of Wuerzburg Wuertzburg Germany

Department of Urology Weill Medical College of Cornell University New York NY; Urology Service Department of Surgery Memorial Sloan Kettering Cancer Center New York NY

Dipartimento di Urologia Universita` Vita Salute Ospedale S Raffaele Milan Italy

Facharzt fur Urologie Abteilung fur Urologie Chirurgische Universitatsklinik Freiburg Germany

Formerly Department of Biostatistics EORTC Headquarters Brussels Belgium

Institute of Urology Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Oncologic and Reconstructive Urology Department of Urology University Hospitals Leuven Leuven Belgium

Policlinico Tor Vergata University of Rome Rome Italy

Urology Service Department of Surgery Memorial Sloan Kettering Cancer Center New York NY

Urology Unit S Maria Annunziata Hospital University of Florence Florence Italy

See more in PubMed

Kamat AM, Witjes JA, Brausi M, Soloway M, Lamm D, Persad R, Buckley R, Böhle A, Colombel M, Palou J. Defining and Treating the Spectrum of Intermediate-Risk NMIBC. J Urol. 2014;192:305–15. PubMed PMC

Rentsch CA, Birkhäuser FD, Biot C, Gsponer JR, Bisiaux A, Wetterauer C, Lagranderie M, Marchal G, Orgeur M, Bouchier C, Bachmann A, Ingersoll MA, Brosch R, Albert ML, Thalmann GN. Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy. Eur Urol. 2014;66:677–88. PubMed

Vegt PDJ, Witjes JA, Witjes WPJ, Doesburg WH, Debruyne FMJ, Meijden APMvd. A randomized study of intrasvesical Mitomycin-C, Bacillus Calmette-Guerin Tice and Bacillus Calmette-Guerin RIVM in pTa-pT1 papillary carcinoma and carcinoma in situ of the bladder. J Urol. 1995;153:929–933. PubMed

Sengiku A, Ito M, Miyazaki Y, et al. A prospective comparative study of intravesical bacillus Calmette-Guerin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer. J Urol. 2013;190:50–4. PubMed

Gontero P, Sylvester R, Pisano F, Joniau S, Vander Eeckt K, Serretta V, Larré S, Di Stasi S, Van Rhijn B, Witjes AJ, Grotenhuis AJ, Kiemeney LA, Colombo R, Briganti A, Babjuk M, Malmström PU, Oderda M, Irani J, Malats N, Baniel J, Mano R, Cai T, Cha EK, Ardelt P, Varkarakis J, Bartoletti R, Spahn M, Johansson R, Frea B, Soukup V, Xylinas E, Dalbagni G, Karnes RJ, Shariat SF, Palou J. 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. 2015;67:74–82. PubMed

de Reijke TM, D deBoer EC, Kurth KH, Schamhart DHJ. Urinary Interleukin-2 monitoring during prolonged BCG treatment: can it predict the optimal number of instillations? J Urol. 1999;161:67–71. PubMed

Kaisary AV. Intravesical BCG therapy in the management of multiple superficial bladder carcinoma. Comparison between Glaxo and Pasteur strains. Br J Urol. 1987;59:554–8. PubMed

Fellows GJ, Parmar MK, Grigor KM, Hall RR, Heal MR, Wallace DM. Marker tumour response to Evans and Pasteur bacille Calmette-Guérin in multiple recurrent pTa/pT1 bladder tumours: report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party) Br J Urol. 1994;73:639–44. PubMed

Ikeda N, Honda I, Yano I, Koyama A, Toida I. Bacillus calmette-guerin Tokyo172 substrain for superficial bladder cancer: characterization and antitumor effect. J Urol. 2005;173:1507–12. PubMed

Secanella Fandos S, Luquin M, Julian E. Connaught and Russian strains showed the highest direct antitumor effects of different bacillus Calmette-Guérin substrains. J Urol. 2013;189:711–18. PubMed

100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19