Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer

Alberto 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, María José Ribal, Antonio Alcaraz, Lodewyk F.A. Wessels, Roland Seiler, Jonathan L. Wright, Lourdes Mengual, Joost Boormans, Bas W.G. van Rhijn, Peter C. Black, Michiel S. van der Heijden*

*Corresponding author for this work

Research output: Contribution to journalEditorialAcademicpeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)313-317
Number of pages5
JournalEuropean Urology
Issue number4
Early online date11 Aug 2022
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information: Funding/Support and role of the sponsor: This project was partially funded by the NWO (Dutch Research Council) and financial contributions from DUOS (Dutch Uro-oncology group) and Astellas Pharma Netherlands. The sponsor played no direct role in the study.

Publisher Copyright: © 2022 European Association of Urology


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