Zusammenfassung
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 ...
Zusammenfassung
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.