Impact of Asymptomatic Bacteriuria on the Outcomes and Tolerability of Bacillus Calmette-Guérin Immunotherapy

Intravesical Bacillus Calmette–Guérin (BCG) remains the cornerstone adjuvant treatment for high-risk non–muscle-invasive bladder cancer (NMIBC), yet its use is frequently complicated by local and systemic adverse effects leading to treatment discontinuation. At the same time, asymptomatic bacteriuria (ABU) is common in this patient population, and its clinical relevance in the context of BCG immunotherapy has remained uncertain. While ABU has traditionally been approached as a potential risk factor for infectious complications, emerging biological rationale suggests that bacterial colonization of the urothelium may modulate local immune responses in a manner relevant to BCG efficacy.

In our multicenter retrospective study including 795 NMIBC patients treated with intravesical BCG between 2009 and 2018, we evaluated whether ABU prior to initiation of therapy influences oncological outcomes or treatment tolerability. ABU, defined as a positive urine culture in the absence of urinary symptoms, was present in 19% of patients. With a median follow-up of 66 months, we observed no statistically significant differences between bacteriuric and uninfected patients in 5-year recurrence-free survival (69% vs. 63%; HR 0.83, 95% CI 0.60–1.14) or progression-free survival (89% vs. 88%; HR 0.86, 95% CI 0.50–1.49). These findings indicate that pre-treatment ABU does not adversely impact the oncological efficacy of BCG.

Equally relevant from a clinical perspective, ABU did not compromise treatment tolerability. The 3-year discontinuation-free survival was identical in both groups (51%). Importantly, rates of severe complications, including BCG infection requiring antituberculous therapy and symptomatic urinary tract infections necessitating hospitalization, were low and did not differ between groups. These observations suggest that the presence of ABU does not potentiate BCG-related toxicity nor increase clinically meaningful infectious risk.

Our results align with earlier smaller series suggesting oncological neutrality of ABU in the context of BCG, while also extending the evidence base by providing robust long-term outcomes and, importantly, the first comparative analysis of overall treatment tolerability. Although prior studies have raised the possibility of improved recurrence-free survival in bacteriuric patients, potentially reflecting immune priming by microbial exposure, such an effect was not statistically confirmed in our cohort despite a similar non-significant trend favoring ABU.

Several limitations inherent to the retrospective design should be acknowledged, including potential selection bias, reliance on single pre-treatment urine cultures, and limited granularity regarding mild adverse events and urinary microbiome composition. Notably, the majority of positive cultures represented mixed flora, underscoring the limitations of conventional culture techniques in capturing the complexity of the bladder microbiome.

From a clinical standpoint, these findings challenge the routine practice of screening for and treating asymptomatic bacteriuria prior to BCG instillation. In the absence of symptoms, delaying or modifying BCG therapy due to ABU does not appear justified based on oncological or safety considerations. Future studies incorporating microbiome-based methodologies are warranted to better define the interaction between microbial colonization and BCG-induced antitumor immunity.

In conclusion, asymptomatic bacteriuria prior to BCG initiation does not impair oncological outcomes nor increase treatment-related toxicity. Intravesical BCG can be safely administered in patients with ABU, supporting a more permissive and clinically pragmatic approach to urine culture findings in this setting.

Written by: Dr. Antti Nummi, Urology Department, University Hospital of Helsinki, Helsinki, Finland.

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