Time-dependent effects of BCG plus immune checkpoint inhibitors in BCG-naive high-risk non-muscle-invasive bladder cancer: a reconstructed patient-level analysis.

Authors

Shugo Yajima, Soichiro Yoshida, Wei Chen, Hiroshi Fukushima, Hajime Tanaka, Hiroyuki Sato, Akihiro Hirakawa, Hitoshi Masuda, Yasuhisa Fujii

Published in

International urology and nephrology. Sep 04, 2026. Epub Sep 04, 2026.

Abstract

Three phase 3 trials (CREST, POTOMAC, ALBAN) adding an immune checkpoint inhibitor (ICI) to Bacillus Calmette-Guérin (BCG) in BCG-naive high-risk non-muscle-invasive bladder cancer (NMIBC) reported different results. We used reconstructed individual patient-level data (rIPD) to examine the overall event-free survival (EFS) effect and its change over time.
This post hoc analysis used data reconstructed from published Kaplan-Meier curves rather than original trial datasets, harmonized as EFS. A trial-stratified Cox model estimated the pooled hazard ratio (HR). Two-parameter Weibull models described the timing of events (scale, β) and the temporal pattern of risk (shape, α), with proportional hazards assessed by Schoenfeld residuals and log-log plots. The trials differed in agent, endpoint definition, and BCG schedule.
Reconstructed event counts and HRs closely matched reported values. The pooled EFS HR was 0.76 (95% confidence interval [CI] 0.63-0.91), and 0.68 (95% CI 0.54-0.85) after excluding ALBAN. Weibull-based cumulative HRs suggested differing time patterns: the fitted cumulative HR decreased over time in CREST, remained broadly stable in POTOMAC, and approached 1 in ALBAN. Model-based 5-year EFS differences (11.5%, 8.4%, and 0.4%) were exploratory, relying on extrapolation in CREST and sparse tail data in ALBAN.
ICI plus BCG was associated with improved EFS, mainly reflecting CREST and POTOMAC. A single-pooled HR may obscure regimen-level differences in how the benefit evolves over time. Given the reconstructed data, between-trial differences, and restriction to efficacy, these findings are hypothesis-clarifying rather than practice-changing.

PMID:
42696081
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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