Gil Jimenez, Albert and van Dorp, Jeroen and Contreras-Sanz, Alberto and van der Vos, Kristan and Vis, Daniel J. and Braaf, Linde and Broeks, Annegien and Kerkhoven, Ron and van Kessel, Kim E. M. and Ribal, Maria Jose and Alcaraz, Antonio and Wessels, Lodewyk F. A. and Seiler, Roland and Wright, Jonathan L. and Mengual, Lourdes and Boormans, Joost and van Rhijn, Bas W. G. and Black, Peter C. and van der Heijden, Michiel S. (2023) Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer. EUROPEAN UROLOGY, 83 (4). pp. 313-317. ISSN 0302-2838, 1873-7560
Full text not available from this repository. (Request a copy)Abstract
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is rec-ommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pre-treatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No cor-relation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alter-ations discriminated between responders and nonresponders to NAC. No further associ-ations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive associ-ation between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomark-ers were not validated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SENSITIVITY; SURVIVAL; DEFECTS; Muscle-invasive bladder cancer; Neoadjuvant chemotherapy; DNA sequencing; Response prediction; Somatic mutations; Cisplatin-based chemotherapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 05:55 |
| Last Modified: | 01 Feb 2024 05:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60756 |
Actions (login required)
 |
View Item |
