Posted: Tuesday, July 18, 2023
For patients with muscle-invasive bladder cancer, the use of personalized genome-wide mutational integration may be a clinically beneficial way to detect measurable residual disease [MRD] and monitor treatment response, according to a presentation given at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4589). This approach is ultrasensitive and noninvasive, and it may have significant implications for early intervention and improved outcomes in this patient population, suggested Iver Nordentoft, PhD, MSc, of Aarhus University Hospital, Denmark, and colleagues.
A total of 110 patients with muscle-invasive bladder carcinoma were recruited for the study. All patients underwent neoadjuvant chemotherapy followed by radical cystectomy. Plasma samples were collected from patients during their neoadjuvant chemotherapy, before radical cystectomy, and after radical cystectomy to detect mutations in cell-free DNA. To identify genome-wide genomic alterations, whole-genome sequencing was performed.
Analysis of circulating tumor DNA (ctDNA) successfully identified patients with evidence of recurrence after radical cystectomy, with a 78% sensitivity and 95% specificity. At the 12-month follow-up, the sensitivity of this assay increased to 86%, and the specificity remained constant. In addition, a positive association was identified between recurrence-free survival (P < .0001) and overall survival (P < .0001) with patients’ status of ctDNA. Moreover, while patients were receiving neoadjuvant chemotherapy, the clearance of ctDNA was revealed to be associated with recurrence-free survival (P = .0051).
Furthermore, analyses revealed that the driver genes primarily affected included KDM6A, KMT2D, PIK3CA, RB1, and TP53. Novel chemotherapy-induced mutational signatures were identified in the plasma samples after the completion of treatment, in addition to an increased quantity of copy numbers on chromosomes 19q and 20.
Disclosure: Dr. Nordentoft reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.