Circulating Tumor DNA and Response to Cisplatin-based Chemotherapy in Patients with Metastatic Urothelial Carcinoma Enrolled in CALGB 90601 (Alliance)

Background and objective: Cisplatin-based chemotherapy has been a cornerstone of therapy for advanced/metastatic urothelial cancer (mUC). However, no genomic characteristics have been validated as prognostic biomarkers for this therapy. We sought to identify prognostic biomarkers using plasma cell-free (cf)DNA collected in a phase 3 cooperative group trial. Methods: We analyzed pretreatment cfDNA from a cohort nested in CALGB 90601 (Alliance), a first-line trial of gemcitabine/cisplatin with bevacizumab or placebo in mUC. We examined associations between cfDNA features and overall survival (OS), progression-free survival (PFS), and treatment response. Key findings and limitations: = 0.019). Conclusions and clinical implications: were associated with poor prognosis. Patient summary: We looked at the link between tumor DNA present in blood and outcomes after chemotherapy for patients with advanced bladder cancer. Higher amounts of tumor DNA in blood and mutations in specific cancer genes were linked to worse survival. The results may help in the design of new studies to improve survival for patients with advanced bladder cancer.This trial is registered on ClinicalTrials.gov as NCT00942331.