Background
Currently, no biomarkers of response to mitomycin C have been identified in non-muscle-invasive bladder cancer patients. Predictive biomarkers could improve the treatment outcome and eliminate adverse events from unnecessary treatment.
Conclusions
Mutation status of APC, SPTAN1, and FGFR3 and the level of mutational contribution from APOBEC-related signatures were identified as potential predictive biomarkers for chemoresection with mitomycin C in non-muscle-invasive bladder cancer patients. A prospective validation study is however needed. Patient summary: We investigated DNA from noninvasive bladder tumours in order to predict treatment response to chemotherapy. Four biomarkers showed promising results, which should be tested in future studies.
Objective
To identify and validate predictive biomarkers of chemoresection with mitomycin C. Design setting and participants: The intervention group of a randomised controlled trial was identified for analyses. The study was conducted between January 2018 and June 2019 in two major urological departments in Denmark. Patients had a history of Ta low-grade/high-grade disease and were included upon recurrence. The intervention group (58 patients) received chemoresection with mitomycin C. Tumour and reference germline DNA from prior tumours were analysed by whole exome sequencing. Predictive biomarkers were validated in the context of Ta low-grade tumours from the UROMOL study. Outcome measurements and statistical analysis: Response to chemotherapy (intervention group from the randomised controlled trial) and recurrence-free survival (UROMOL cohort) were measured. Groups were compared using Fisher's exact test and Wilcoxon rank sum test.