Re-analysis of intravesical gemcitabine in the era of Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer Journal Article
| Authors: | De Jesus Escano, M. R.; Vertosick, E. A.; D'Souza, N.; Benfante, N.; Lenis, A. T.; Reisz, P. A.; Gaffney, C.; Goh, A.; Donahue, T. F.; Cha, E.; Donat, S. M.; Herr, H. W.; Dalbagni, G.; Bajorin, D.; Sarungbam, J.; Al-Ahmadie, H.; Bochner, B. H.; Sjoberg, D. D.; Pietzak, E. J. |
| Article Title: | Re-analysis of intravesical gemcitabine in the era of Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer |
| Abstract: | Purpose: Uncertainty exits over the best treatments for patients whom Bacillus Calmette-Guérin (BCG) has failed. We aim to contextualize novel therapies approved based on single-arm, nonrandomized trials and those supported only by retrospective data by re-analyzing oncologic outcomes achieved with intravesical gemcitabine. Materials and Methods: Patients with non–muscle-invasive bladder cancer (NMIBC) who were treated for BCG failure with single agent intravesical gemcitabine at our institution were analyzed to compare clinical outcomes (high-grade recurrence/progression) across different BCG failure definitions. Associations between clinicopathologic variables with outcomes after gemcitabine were estimated using Cox models. Results: Of the 127 patients, 57% met the historical definition of BCG-refractory NMIBC and 33% met BCG-unresponsive criteria using a 12-month cut-off. Twelve-month recurrence-free survival was similar between BCG-refractory (47%; 95% CI: 36%, 60%) and BCG-unresponsive (52%; 95% CI: 38%, 71%) definitions. BCG-unresponsive patients who received gemcitabine in a clinical trial had significantly worse recurrence-free survival compared to those receiving the same treatment outside a trial (12-month recurrence-free survival difference: 41%; P = 0.02). A positive pretreatment urine cytology was associated with increased risk of recurrence (P = 0.005) and progression (P = 0.002) and may better indicate minimal residual disease than carcinoma in-situ on pretreatment biopsies. Conclusions: Our data raise concern over US Food and Drug Administration approval based on single-arm, nonrandomized trials using expert-based BCG-unresponsive criteria and for the use of combination gemcitabine-docetaxel as a de facto standard treatment based on retrospective data alone. Improved assessments of minimal residual disease, such as pretreatment urinary cytology, are needed to improve risk stratification in NMIBC. © 2025 |
| Keywords: | clinical trial; intravesical gemcitabine; bacillus calmette-guérin failure; bacillus calmette-guérin-unresponsive non–muscle invasive bladder cancer |
| Journal Title: | Urologic Oncology: Seminars and Original Investigations |
| ISSN: | 1078-1439 |
| Publisher: | Elsevier Inc. |
| Publication status: | Published |
| Date Published: | 2025-09-01 |
| Start Page: | 520.e19 |
| End Page: | 520.e28 |
| Language: | English |
| DOI: | 10.1016/j.urolonc.2025.04.006 |
| PROVIDER: | scopus |
| PUBMED: | 40414743 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Eugene J. Pietzak -- Source: Scopus |
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