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.
European urology. 2022 Aug 11 [Epub ahead of print]
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
Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands., Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands., The Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, Canada., Core Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands., Core Facility Genomics, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Laboratory and Department of Urology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Universitat de Barcelona, Barcelona, Spain., Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands; Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Delft, The Netherlands., Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Urology, Hospital Center Biel, Biel, Switzerland., Department of Urology, University of Washington School of Medicine, Seattle, WA, USA., Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany., Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35965206