In Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy, Dynamics of Circulating Tumor DNA Following Cystectomy: Association with Patient Outcomes

BACKGROUND AND OBJECTIVE: Despite various novel therapeutic possibilities for patients with muscle-invasive bladder cancer (MIBC), therapy response varies highly. Circulating tumor DNA (ctDNA) represents a fraction of cell-free DNA released into the bloodstream by apoptotic cell turnover or cell death in the tumor. We investigated whether ctDNA measurements before and after radical cystectomy are associated with disease recurrence. METHODS: We prospectively collected plasma, tumor tissue, and germline samples before and after radical cystectomy. Seventy patients had complete data for both pre- and postsurgery analyses. Commonly mutated genes in plasma and tissue, particularly TERT and TP53, were assessed using the AVENIO ctDNA platform (research use only; Roche, Branchburg, NJ, USA) and then evaluated for a potential association with patient outcome measures, including survival and disease recurrence. KEY FINDINGS AND LIMITATIONS: In the overall study population, patients with negative ctDNA status in postsurgery plasma had significantly longer recurrence-free survival than those with positive ctDNA status (p = 0.01). The ctDNA positivity fell from 46% before surgery to 23% after surgery, and a positive postoperative result predicted recurrence independently. Patients who were ctDNA positive before surgery and converted to ctDNA negative after surgery showed longer survival than those remaining ctDNA positive (median survival 36 vs 18 mo). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results highlight that perioperative ctDNA status is associated with patient prognosis in MIBC.