Bacillus Calmette-Guérin therapy in the management of upper tract urothelial carcinoma in-situ: a systematic review.

BACKGROUND

Upper urinary tract carcinoma in-situ (UUT-CIS) is an aggressive disease traditionally managed with radical nephroureterectomy (RNU), often resulting in loss of renal function. Topical Bacillus Calmette-Guérin (BCG) therapy has been explored as a kidney-sparing alternative, although evidence remains limited and heterogeneous. This review aimed to synthesise oncological and safety outcomes of topical BCG therapy for UUT-CIS.

METHODS

A systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and grey literature (registration No. CRD420261277998). Eligible studies were published 01/01/2000-14/09/25, enrolled adult patients with UUT-CIS treated with topical BCG and reported oncological or toxicity outcomes. Primary outcomes were rates of complete response, recurrence and progression. Where methodological homogeneity permitted, meta-analysis was planned. Risk of bias was assessed using Risk Of Bias In Non-randomised Studies of Interventions (ROBINS)-I V2.

RESULTS

Fourteen observational studies comprising 298 renal units (267 patients) were included (weighted mean age of 71.8 years; 19.2% female). Complete response rates following BCG induction ranged 59-100% per renal unit. Recurrence rates after initial response ranged 0-70% and progression rates ranged 0-43%. The proportion of renal units requiring salvage RNU ranged 0-25%. Renal unit preservation ranged 45-100%. Median follow-up varied substantially at 13-88 months. Adverse events were predominantly local and self-limited; severe systemic toxicity was uncommon, and treatment-related mortality was reported in one patient. Substantial heterogeneity existed in follow-up duration, delivery technique, surveillance protocols, and outcome definitions, negating meta-analysis. Most included studies demonstrated a moderate risk of bias across key ROBINS-I domains, reflecting observational study design and the absence of randomized trials.

CONCLUSIONS

Topical BCG therapy for UUT-CIS is associated with high initial response rates and meaningful renal preservation and may represent a kidney-sparing option in carefully selected or imperative clinical scenarios. However, recurrence and progression rates remain variable. Topical BCG therapy should not be considered equivalent to RNU, which remains the oncological standard of care.