Metachronous non-muscle invasive bladder cancer after UTUC has worse recurrence and progression with BCG than primary disease

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Urologic oncology Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Tan Yu Guang, Fong Khi Yung, Abern Michael R, Lim Benjamin Jia Han, Leow Jeffrey Jj, Chong Tsung Wen… PubMed ↗ DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Consider that metachronous NMIBC after UTUC may have worse BCG outcomes than primary NMIBC, informing risk stratification.

This is a systematic review and meta-analysis of studies comparing outcomes in patients with primary non-muscle invasive bladder cancer (p-NMIBC) versus metachronous non-muscle invasive bladder cancer (m-NMIBC) following prior upper tract urothelial carcinoma treatment, all receiving BCG. The meta-analysis included 1292 patients.

For high-grade recurrence-free survival, m-NMIBC was associated with worse outcomes than p-NMIBC (hazard ratio 0.47 in one-stage analysis; HR 0.44 in two-stage analysis; 95% CI 0.38-0.59 and 0.38-0.50, respectively; P < 0.001 for both). Progression-free survival was also worse for m-NMIBC (HR 0.54 one-stage; HR 0.45 two-stage; 95% CI 0.35-0.83 and 0.22-0.90; P = 0.005 and P = 0.035). Cancer-specific survival and overall survival showed no significant differences (CSS HR 0.53, 95% CI 0.24-1.17, P = 0.116; OS HR 1.24, 95% CI 0.64-2.42, P = 0.520).

The authors acknowledged a moderate overall risk of bias across the included studies. Safety data were not reported. The review highlights implications for clinical trial design and risk stratification, but the evidence is observational and does not establish causation.

Study Details

Study typeMeta analysis

Sample sizen = 1,292

EvidenceLevel 1

PublishedJun 2026

PMID41956941

View Original Abstract ↓

INTRODUCTION: Emerging evidence suggests that metachronous non-muscle invasive bladder cancer (m-NMIBC) recurrence after prior upper tract urothelial carcinoma (UTUC) treatment is distinct from primary NMIBC (p-NMIBC). Correspondingly, their disease trajectories and treatment responses may differ vastly. This systematic review aims to evaluate the differences in Bacillus Calmette-Guérin (BCG) response between m-NMIBC and p-NMIBC. METHODS: A comprehensive literature search (PubMed, Embase, and Scopus) was performed to identify relevant studies that reported BCG outcomes for p-NMIBC and m-NIMBC. Endpoints analyzed were high-grade recurrence-free survival (HG-RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). This study followed the PRISMA guidelines. Both one-stage and two-stage meta-analyses were performed. RESULTS: Six cohort studies with 1,292 patients were identified. Three studies utilized propensity-matched scoring to account for differences in baseline clinical characteristics. BCG prescription was observed in 89% of the whole cohort, with 4 studies treating all included patients with BCG. Patients with m-NMIBC demonstrated worse HG-RFS (one-stage meta-analysis: HR 0.47, 95% CI 0.38-0.59, P < 0.001; two-stage meta-analysis: HR 0.44, 95% CI 0.38-0.50, P < 0.001, I² = 0%). M-NMNIBC also demonstrated worse PFS compared to p-NMIBC (one-stage meta-analysis: HR 0.54, 95% CI 0.35-0.83, P = 0.005; two-stage meta-analysis: HR 0.45, 95% CI 0.22-0.90, P = 0.035, I² = 0%). There were no significant differences for CSS (one-stage meta-analysis: HR 0.53, 95% CI 0.24-1.17, P = 0.116) and OS (one-stage meta-analysis: HR 1.24, 95% CI 0.64-2.42, P = 0.520). Overall risk of bias was moderate across the included studies. CONCLUSIONS: This review observed that m-NMIBC exhibits a poorer response to BCG compared to p-NMIBC, with significantly higher rates of HG-recurrence and disease progression. These observations reflect a potential biological distinction between the 2 entities, and highlight important implications in clinical trial design and risk stratification.