(UroToday.com) Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). A pathologic response (ypT0/Tis/Ta/T1N0) after NAC has been associated with improved long-term survival. However, clinicians are unable to predict which patients will have a pathologic response. Somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and/or FANCC have been shown previously to correlate with pathologic response after NAC in MIBC. However, none of these biomarkers have been validated in larger independent cohorts and are consequently not used in clinical practice. The objective of this study was to validate these genomic biomarkers in an independent retrospective cohort of 165 MIBC patients who had undergone NAC and radical cystectomy.
A total of 165 MIBC patients from five different hospitals were included. All patients were treated with at least two cycles of NAC followed by radical cystectomy. DNA was isolated from diagnostic transurethral resection material and used for DNA sequencing. Genomic alterations were inferred using population databases.
Somatic deleterious mutations in ERCC2 were found in 9/68 (13%) evaluable responders and in 2/95 (2%) evaluable non-responders (P=0.009). 5-year overall survival rate was 75% (95% confidence interval (CI): 50-100%) for patients with mutations in ERCC2 and 52% (95% CI: 45%-62%) for patients without mutations in ERCC2, however, this was not statistically significant (P=0.2). No correlation was observed between pathological response and alterations in ERBB2 or in ATM, RB1, and/or FANCC. 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, they validated that deleterious mutations in ERCC2 are a genomic biomarker for pathologic response to NAC. Other previously reported genomic biomarkers were not validated.
Presented by: Alberto Gil-Jimenez, Netherlands Cancer Institute, Amsterdam, Netherlands
Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain