BCG Medac® for the treatment of non-muscle-invasive bladder tumors: adverse events and predictive factors for tolerance

Adjuvant treatment with endovesical BCG instillations after resection of a bladder urothelial tumor remains the gold standard for intermediate- or high-risk non-muscle-invasive tumors. However, it is associated with frequent and sometimes serious adverse events (AEs). To comprehensively assess the frequency, intensity, and potential risk factors of BCG instillation AEs following the field experience of a single French center using only the Medac® BCG. A database obtained through a query to the Medical Information Department identified 127 patients who received 1498 Medac® BCG instillations from July 2016 to July 2021. The study focused on the instillations performed in the 1st year (induction treatment and the first two maintenance cycles). Data included demographics, tumor characteristics, treatment conduct and adverse events and their characteristics. Logistic regression completed the descriptive statistics to search for associations between AEs and potential risk factors. Of the 127 patients, 81% had at least one AE. AEs concerned the genitourinary sphere in 80% of cases. The proportion of side effects classified as severe was 4%. BCG treatment was discontinued in 41 patients (32.2% of patients), the main reason being the occurence of AEs (21 out of 41 patients, i.e. 51%). Age, diabetes, active smoking, previous BCG instillations, residual tumor at 2nd look TURB, use of ofloxacin and non-negative urine culture were significantly associated to AEs. Conversely, gender, previous MMC instillation, stage, grade, 2nd look procedure and ASA score were not. Multivariate analysis showed that the presence of residual tumour at 2nd look and active smoking were independent predictive factors. However, these factors were not systematically found for all instillations. The analysis was also performed per instillation. Data on a total of 1498 BCG instillations were collected, with a median of 11 instillations per patient. Of these instillations, 29.6% resulted in AEs. In addition, 125 instillations (8%) were associated with more than one AE. A total of 569 AEs were recorded, with an average of 27.2% AEs per instillation. AEs led to the postponement of 16 instillations out of 93 (17%) in 15 patients. In our study, most patients who received endovesical instillations of BCG experienced AEs, mainly localized to the genitourinary sphere and of low severity. Discontinuation of BCG and serious AEs requiring more than monitoring or symptomatic treatment were not frequent during the first year of treatment. We found no robust predictor of AEs. The problems of predicting the efficacy of BCG on the one hand, and its tolerability on the other, remain unresolved and warrant a future sufficiently powered prospective study.