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.
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.
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.
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.
Urologic oncology. 2026 Apr 08 [Epub ahead of print]
Yu Guang Tan, Khi Yung Fong, Michael R Abern, Benjamin Jia Han Lim, Jeffrey Jj Leow, Tsung Wen Chong, Kae Jack Tay, Kenneth Chen, John Sp Yuen, Johan Chan, Jason Ys Chan, Syed A Hussain, Jeremy Yc Teoh, Ashish M Kamat
Department of Urology, Singapore General Hospital, Singapore; Department of Urology, Duke University School of Medicine, Durham, NC. Electronic address: ., Department of Urology, Singapore General Hospital, Singapore., Department of Urology, Duke University School of Medicine, Durham, NC., Department of Urology, Tan Tock Seng Hospital, Singapore., National Cancer Centre Singapore, Singapore., Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong., University of Texas MD Anderson Cancer Centre, Houston, TX.