USF-LVHN SELECT
Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer: Survival Benchmarks, Bladder-sparing Strategies, and Implications for Trial Design.
Publication/Presentation Date
12-19-2025
Abstract
BACKGROUND AND OBJECTIVE: Intravesical recurrence after induction bacillus Calmette-Guérin (BCG) therapy is common in non-muscle-invasive bladder cancer (NMIBC), but longitudinal, real-world data using contemporary definitions of the BCG-exposed (BCG-E) phenotype remain limited, which constrains trial design. We assessed long-term clinical outcomes and clinical trajectories for a large BCG-exposed cohort treated at a single tertiary care center to establish pragmatic benchmarks to inform patient counseling, surveillance strategies, and the design and interpretation of bladder-sparing studies.
METHODS: We conducted a retrospective cohort study for adults with histologically confirmed high-grade NMIBC treated with intravesical BCG at Moffitt Cancer Center between 1988 and 2024. Relevant clinical data were extracted from electronic medical records into a prespecified database, including detailed BCG doses and timing and features of each recurrence episode. Initial management followed contemporary standards, with subsequent intravesical therapy or radical cystectomy (RC) after shared decision-making. Patients were classified as BCG-unresponsive (BCG-UR) or BCG-E, with BCG adequacy defined as previously published. Time-to-event endpoints were analyzed using Kaplan-Meier estimates and multivariable Cox proportional-hazards models; baseline characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests.
KEY FINDINGS AND LIMITATIONS: Of 1076 NMIBC patients treated with BCG, 470 were classifiable: 245 (52.1%) were BCG-E, of whom 173 (70.6%) were resistant and 72 (29.4%) experienced delayed relapse, and 225 (47.9%) were BCG-UR. In the BCG-E group, 50.2% experienced recurrence and 15.5% experienced progression; median recurrence-free survival (RFS) was 27.2 mo. The 5-yr survival rate estimates were 32.25% for RFS, 79.3% for progression-free survival (PFS), 84.5% for metastasis-free survival (MFS), and 65.0% for overall survival (OS). Recurrence was associated with worse PFS (p < 0.001) and MFS (p = 0.03), but not OS (p = 0.2). RC was performed in 45 patients (18.4%). No consistent survival differences were observed across salvage therapies (62.0% BCG, 18.4% gemcitabine + docetaxel, 5.3% single-agent chemotherapy, 1.2% trials, 13% surveillance),. Multivariable OS estimates were computed. Addition of recurrence to the model did not improve discrimination; age and performance status were the strongest predictors of OS.
CONCLUSIONS AND CLINICAL IMPLICATIONS: We present comprehensive outcomes for and an in-depth characterization of clinical trajectories in BCG-E NMIBC, for which salvage intravesical BCG is predominant and oncologic results are durable. These data provide pragmatic benchmarks for the interpretation and design of bladder-sparing trials in this setting.
ISSN
2405-4569
Published In/Presented At
Jazayeri, S. B., DiNatale, R. G., Guske, C., Harrs, C., Linscott, J., Xu, H., Davaro, F., Wen, L., Spiess, P. E., Sexton, W. J., Gilbert, S. M., Zemp, L., Poch, M. A., & Li, R. (2025). Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer: Survival Benchmarks, Bladder-sparing Strategies, and Implications for Trial Design. European urology focus, S2405-4569(25)00367-0. Advance online publication. https://doi.org/10.1016/j.euf.2025.12.013
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
41421932
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article