Addition of immune checkpoint inhibitors to intravesical BCG for high-risk BCG-naïve non-muscle invasive bladder cancer: Systematic review and meta-analysis

OBJECTIVE: The objective of this study is to assess the efficacy, safety and change in quality of life associated with ICI-BCG (I + M) compared to BCG (I + M) in patients with BCG-naïve HR-NMIBC.

MATERIAL AND METHODS: A systematic search was run on PubMed, Embase and CENTRAL from inception to 29 October 2025. Phase 3 randomized controlled trials comparing safety, efficacy and quality of life (QOL) for patients with BCG-naïve HR-NMIBC receiving ICI-BCG (I + M) versus BCG (I + M): hazard ratios (HR) and 95% confidence interval (95% CI) for HG-RFS (high-grade recurrence free survival), odds ratio (OR) and 95% CI for Grade ≥3 treatment-related adverse events (G3 + TRAEs), and mean difference (MD) and 95% CI for changes in quality of life (QOL measured using EORTC QLQ C30). A priori defined subgroups included presence of CIS, presence of papillary tumours, age <65 or ≥65 years, male/female, and BCG strain.

RESULTS: Pooled results indicated that ICI-BCG (I + M) was not associated with a reduction in HG-RFS (HR: 0.78; 95% CI: 0.59-1.02). However, on sensitivity analysis excluding ALBAN (for differences in trial design and patients included), ICI-BCG (I + M) was associated with a reduction in HG-RFS (HR: 0.68; 95% CI: 0.54-0.85) with an absolute risk reduction of 4.4-7.3% in 36-month HG-RFS. ICI-BCG (I + M) was associated with an increased risk of G3 + TRAEs (OR: 4.76; 95% CI: 3.01-7.53). ICI-BCG (I + M) was associated with a non-clinically significant decline in QOL (MD: -3.25; 95% CI: -5.11 to -1.39). Heterogeneity between trials was minimal ( τ 2  < 1). Risk of bias was low in all included studies.

CONCLUSION: This pooled analysis provides data for patient-specific counselling on the use of ICI-BCG (I + M) for BCG-naive HR-NMIBC.