In this issue of European Urology, Buisan et al. report early clinical and immunological outcomes of subcutaneous priming with the non-live mycobacterium tuberculosis RUTI vaccine prior to intravesical Bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder cancer (NMIBC). The phase 1 study included 40 patients, with 20 receiving two doses of RUTI before BCG induction and 20 receiving placebos. Given the limited cohort size, a high-risk subgroup of patients with T1 high-grade (HG) disease (excluding carcinoma in situ) was analysed separately to evaluate early treatment effects. In the overall evaluable cohort (n=37), recurrence rates were lower in the RUTI group compared with placebo (21% vs. 44%), with early recurrences (within six months) more frequent in the placebo arm. Among patients with T1 HG disease, recurrence occurred in 1 of 10 RUTI-treated patients versus 5 of 11 in the placebo group, suggesting potential benefit in this high-risk population, particularly in preventing early relapse during BCG induction. The study is notable for its detailed immunological analysis. RUTI-treated patients demonstrated trends toward reduced regulatory T cells and increased CD4+ and CD8+ T-cell responses at earlier time points, along with a more pronounced BCG-specific immune response. These findings support the concept that systemic priming may enhance ‘trained immunity’, potentially strengthening the tumouricidal effects of intravesical BCG. While these early results are promising, particularly for high-risk T1 disease, larger randomised trials are needed to confirm durability and long-term benefit. Ongoing studies, including the large S1602 trial evaluating intradermal BCG priming, are expected to clarify whether priming strategies can meaningfully reduce high-grade recurrences. Further translational research will be essential to define patient selection and optimise immunologic response.
Boosting the immune response to Bacillus Calmette-Guérin
Reviewed by Asif H Ansari
"PRIME" Time for Boosting the Immune Response to Bacillus Calmette-Guérin
