BACKGROUND: Current European Association of Urology (EAU) guidelines support adjuvant intravesical Bacillus Calmette-Guérin (BCG) treatment after Transurethral Resection of Bladder Tumor (TURB) for intermediate- or high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients, aiming to reduce the risk of tumor recurrence. The quality of data, however, does not allow definitive conclusions on whether different strains and dosages of BCG have different efficacies on long-term survival outcomes. OBJECTIVE: To evaluate the long-term survival outcomes of different strains and dosages of BCG in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: All NMIBC patients treated with intravesical BCG therapy from 2001 to 2020 were identified using a territory-wide database in Hong Kong. INTERVENTION: BCG strains and dosages (Connaught strain 81 mg, Connaught strain 27 mg, Tokyo strain 80 mg, and Danish strain 30 mg) were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. A multivariable Cox regression analysis was used to adjust potential confounding factors, and to estimate Hazard Ratio (HR) and 95% confidence interval (CI) of different BCG strains. A further subgroup analysis on adequate versus inadequate BCG treatment was performed. RESULTS AND LIMITATIONS: A total of 2602 NMIBC patients treated with intravesical BCG were identified. Among them, 1291 (49.6%) received Connaught strain 81 mg, 199 (7.6%) received Connaught strain 27 mg, 1014 (39.0%) received Tokyo strain, and 98 (3.8%) received Danish strain. The median follow-up was 11.0 years. No statistically significant differences in OS, CSS, RFS, and PFS were detected among the different groups. At the multivariable analysis, the Connaught strain 27 mg group was inferior to the Connaught strain 81 mg group in terms of OS (HR: 1.26, 95% CI: 1.05-1.51), CSS (HR: 1.69, 95% CI: 1.08-2.66), and PFS (HR: 1.86, 95% CI: 1.20-2.88). Adequate BCG treatment was associated with improved OS (HR: 0.82, 95% CI: 0.73-0.92), CSS (HR: 0.64, 95% CI: 0.47-0.86), RFS (HR: 0.80, 95% CI: 0.70-0.92), and PFS (HR: 0.52, 95% CI: 0.39-0.68). Among patients treated with adequate BCG, at the multivariable analysis the Connaught strain 27 mg group showed worse results than the Connaught strain 81 mg group in terms of CSS (HR: 1.93, 95% CI: 1.07-3.51). Compared with the Connaught strain 81 mg group, both Tokyo and Danish strains had similar survival outcomes in the whole cohort and the adequate BCG treatment subgroup. CONCLUSIONS: Our findings suggest that adequate BCG remains the most important factor in optimizing survival outcomes in patients with intermediate- and high-risk NMIBC. No significant differences in survival outcomes were observed between full-dose Connaught, Tokyo, and Danish strains. Reduced-dose Connaught strain was associated with the worst survival outcomes. PATIENT SUMMARY: We evaluated the efficacy of different strains and dosages of bacillus Calmette-Guérin (BCG) in patients with intermediate- or high-risk non-muscle-invasive bladder cancer in the past two decades in Hong Kong. We conclude no significant differences in long-term survival outcomes in terms of full-dose Connaught, Tokyo, and Danish strains, while reduced-dose Connaught strain was inferior to the full-dose group. Adequate BCG treatment benefits long-term survival.

AOU Città della Salute e della Scienza di Torino Torino School of Medicine Torino Italy

Department of Minimally Invasive and Robotic Urology Wrocław Medical University Wrocław Poland

Department of Urology MD Anderson Cancer Center Houston TX USA

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology La Croix du Sud Hospital Quint Fonsegrives France

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Dallas TX USA; Hourani Center of Applied Scientific Research Al Ahliyya Amman University Amman Jordan; Department of Urology 2nd Faculty of Medicine Charles University Prague Czechia

Department of Urology Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Rabin Medical Center Petah Tikva Israel and Medical University of Vienna Austria

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology San Raffaele Hospital and Scientific Institute Milan Italy

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Hertfordshire and Bedfordshire Urological Cancer Centre Department of Urology Lister Hospital Stevenage UK; School of Life and Medical Sciences University of Hertfordshire Hatfield UK

S H Ho Urology Centre Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Hong Kong China

S H Ho Urology Centre Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Hong Kong China; Department of Experimental and Clinical Biomedical Science University of Florence Florence Italy

Unit of Urology Santa Maria della Misericordia Academic Medical Center Udine Italy

Urology Unit Department of Surgical Sciences Tor Vergata University Hospital University of Rome Tor Vergata Rome Italy

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Young age and adequate BCG are key factors for optimal BCG treatment efficacy in non-muscle-invasive bladder cancer