Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.
Publication/Presentation Date
4-1-2024
Abstract
PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials.
METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients.
RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15%
CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.
Volume
8
First Page
2300274
Last Page
2300274
ISSN
2473-4284
Published In/Presented At
Lenis, A. T., Whiting, K., Ravichandran, V., Tallman, J. E., Alam, S. M., Chu, C. E., Jesus Escano, M., Bochner, E., Katims, A., Reisz, P. A., Truong, H., Clinton, T. N., Telis, L., Dason, S., McPherson, V., Teo, M. Y., Funt, S., Aggen, D., Goh, A. C., Donahue, T. F., … Pietzak, E. J. (2024). Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer. JCO precision oncology, 8, e2300274. https://doi.org/10.1200/PO.23.00274
Disciplines
Medicine and Health Sciences
PubMedID
38691813
Department(s)
Department of Surgery
Document Type
Article