Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial.

OBJECTIVE: To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG.

METHODS: Phase 1 and mechanistic longitudinal, prospective, single-blind randomized study (NCT04806178). Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor (TURBT) in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo (0.9% saline) administered 15 days before the start of intravesical BCG therapy. Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene (IFITM3), Interleukin 1 beta (IL1-BETA), interleukin-2 receptor alpha chain (IL2 RA), Interleukin 6 (IL 6), Interleukin 10 (IL 10), Tumor necrosis factor alpha (TNF-α), Interferon-β, AXL, and one protease CASPASE 8.

RESULTS: After 1 exclusion, twenty patients were randomized to intradermal BCG (n = 11) and intradermal placebo (n = 9). There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy, and no difference in the expression of the cytokines and proteases analyzed between control and intervention, and over time.

CONCLUSIONS: Intradermal BCG administration before intravesical application was safe, with no increase in adverse effects. It also does not seem to change the analyzed targets during the intravesical induction-phase BCG. Other immune targets should be explored in the future. The Brazilian tuberculosis-endemic status, where BCG vaccination is mandatory, might have affected the results.