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

Abstract 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.