Title
Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer
Author
Gil Jimenez, A. (Netherlands Cancer Institute; Oncode Institute)
van Dorp, Jeroen (Netherlands Cancer Institute)
Contreras-Sanz, Alberto (University of British Columbia)
van der Vos, Kristan (Netherlands Cancer Institute)
Vis, Daniel J. (Netherlands Cancer Institute; Oncode Institute)
Braaf, Linde (Netherlands Cancer Institute)
Broeks, Annegien (Netherlands Cancer Institute)
Kerkhoven, Ron (Netherlands Cancer Institute)
van Kessel, Kim E.M. (Erasmus MC)
Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute; Oncode Institute) 
Date
2023
Abstract
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended 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 pretreatment 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 correlation 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 alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. Patient summary: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.
Subject
Cisplatin-based chemotherapy
DNA sequencing
Muscle-invasive bladder cancer
Neoadjuvant chemotherapy
Response prediction
Somatic mutations
To reference this document use:
http://resolver.tudelft.nl/uuid:16e1e99a-b96a-4756-84dc-9458e37dfca3
DOI
https://doi.org/10.1016/j.eururo.2022.07.023
Embargo date
2023-09-09
ISSN
0302-2838
Source
European Urology, 83 (4), 313-317
Bibliographical note
Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public. Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17] (European Urology (2023) 83(4) (313–317), (S0302283822025386), (10.1016/j.eururo.2022.07.023)) The authors regret that the following statement regarding author contributions was missed: Kristan van der Vos is currently a Scientific Editor for Cell Reports Medicine, which is published by Elsevier. Dr van der Vos was not involved in the peer-review process or editorial discussions about this manuscript. The authors would like to apologise for any inconvenience caused.
Part of collection
Institutional Repository
Document type
journal article
Rights
© 2023 A. Gil Jimenez, Jeroen van Dorp, Alberto Contreras-Sanz, Kristan van der Vos, Daniel J. Vis, Linde Braaf, Annegien Broeks, Ron Kerkhoven, Kim E.M. van Kessel, L.F.A. Wessels, More Authors