Bacillus Calmette-Guérin (BCG) with or without Immune Checkpoint Blockade in BCG-Naïve High-Risk Non-Muscle-Invasive Bladder Cancer: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis
In brief
Checkpoint inhibitor plus BCG maintenance reduces recurrence risk by about 23%
In a pooled analysis of three phase-3 trials involving 2,590 BCG-naïve high-risk NMIBC patients, adding an immune checkpoint inhibitor to full-course BCG lowered the chance of disease recurrence or progression by roughly one-quarter compared with BCG alone. The benefit disappeared when the drug was given only with BCG induction, and severe side effects were three-times higher, so careful patient selection is needed.
- Journal
- Critical reviews in oncology/hematology (Q1)
- Published
- 5 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Mohammed Amine Saâd, Abdelkarim Antari, Imad Taleb, Sofia El Omri, Hamadoun Traoré, Imane Chahbounia, et al.
- PMID
- 42556596
- DOI
- 10.1016/j.critrevonc.2026.105510
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 9 August 2026).
- Picked for Geriatrics and Gerontology (top studies of the week, 9 August 2026).
- Picked for Oncology and Radiation Oncology (top studies of the week, 9 August 2026): ICI + BCG improves event‑free survival in high‑risk NMIBC
- Picked for Urology (top studies of the week, 9 August 2026): Meta‑analysis of ICI + BCG vs BCG alone in high‑risk
- Picked for Hematology (top studies of the week, 9 August 2026).
Abstract
BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. Despite standard treatment with transurethral resection followed by BCG instillation, 30-40% of patients relapse. We conducted a meta-analysis evaluating immune checkpoint inhibitor (ICI) plus BCG versus BCG alone in BCG-naïve high-risk NMIBC. METHODS: We performed a systematic review and reconstructed individual patient data (rIPD) meta-analysis of phase 3 randomized controlled trials (RCTs). Individual patient data were reconstructed from published Kaplan-Meier curves using the IPDfromKM method. The primary endpoint was event-free survival (EFS) for ICI plus BCG induction and maintenance (I+M) versus BCG I+M alone. Secondary endpoints included EFS for ICI plus BCG induction only, overall survival, subgroup analyses (age, sex, BCG strain, concomitant CIS), and safety. RESULTS: Three phase 3 trials (CREST, POTOMAC, ALBAN; n=2590) were included. ICI plus BCG I+M significantly improved EFS versus BCG alone (HR 0.77, 95% CI 0.64-0.93; p=0.006), corroborated by pooled aggregate-data analysis (HR 0.77, 95% CI 0.60-0.97; I²=40%). ICI plus BCG induction only conferred no benefit (HR 1.03, 95% CI 0.85-1.25; p=0.754). Overall survival data were immature (HR 0.90; p=0.36). Grade ≥3 adverse events were more frequent with combination therapy (24.5% vs 6.1%). CONCLUSION: ICI combined with full BCG maintenance significantly improves EFS in BCG-naïve high-risk NMIBC. This benefit is contingent on BCG maintenance; induction-only BCG provides no synergistic effect. Incremental toxicity warrants careful patient selection and biomarker-stratified validation before universal adoption.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.