Oncological outcomes of high risk non-muscle invasive bladder tumours affected by bcg shortage for intravesical instillation

Abstract

Objectives: During 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective of the present study is to analyze whether patients affected during the shortage by reduced dose courses, are at a higher risk of tumor recurrence than those receiving full dose schemes. Methods: Retrospective cohort study with a total sample of 154 subjects (60 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG. Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated by survival analysis using the Kaplan-Meier method. Relapse-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. Results: Median follow-up in the 2019 sample was 503 days and 1197 days in the 2017 group, with a median number of instillations of 8 and 12 respectively. There was a 37.7% proportion of tumoral relapse observed in the 2019 group and 29.03% during 2017. Survival analysis revealed mean relapse-free follow-up of 683 days (95%CI 601.3-765.5) in the 2019 group and of 1359 days (95%CI 1244.3-1474) in 2017. Further analysis using LogRank test revealed observed differences to be statistically significant (p=0.02) Multivariable analysis revealed a proportional Hazard ratio (HR) for relapse-free survival rate of 2.2 (95% CI: 1.13-4.25; p=0.019) regarding the 2019 sample treated with a reduced-dose course. Conclusions: BCG shortage and the subsequent reduced-dose schemes used for intravesical instillation, due to limited availability, had a significant impact on tumor relapse rates during follow-up. These findings are consistent with other published studies and show the need for full-dose BCG courses in order to prevent higher relapse rates after TURB.