Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC.
We performed a retrospective analysis of real-world data for a commercial ctDNA test (Signatera; Natera, Austin, TX, USA) performed in 167 patients (852 plasma samples) before RC and during molecular residual disease (MRD; adjuvant decision) and surveillance windows. We assessed the correlation between recurrence and ctDNA status before and after RC using Cox regression analysis.
During study-defined postoperative MRD and surveillance windows, detectable ctDNA was associated with shorter disease-free survival (DFS) when compared to undetectable ctDNA (MRD: hazard ratio 6.93; p < 0.001; surveillance: hazard ratio 23.02; p < 0.001). Of note, patients with undetectable ctDNA did not appear to benefit from adjuvant therapy (p = 0.34). Detectable ctDNA in the pre-RC (p = 0.045), MRD (p = 0.002), and surveillance (p < 0.001) windows was the only risk factor independently associated with shorter DFS. Limitations include the retrospective and nonrandomized nature of the study.
ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making.
We found that outcomes for patients with muscle-invasive bladder cancer are strongly linked to detection of tumor DNA in blood samples. The results show the value of tumor-informed testing for tumor DNA in blood for decisions on the best treatment for each individual patient.
European urology oncology. 2024 Jul 15 [Epub ahead of print]
John P Sfakianos, Arnab Basu, George Laliotis, Shivaram Cumarasamy, Jordan M Rich, Ajitha Kommalapati, Michael Glover, Tamara Mahmood, Neeraja Tillu, Christopher J Hoimes, Grayce Selig, Revathi Kollipara, Tyler F Stewart, Samuel Rivero-Hinojosa, Punashi Dutta, Mark Calhoun, Shruti Sharma, Meenakshi Malhotra, Adam C ElNaggar, Minetta C Liu, James E Ferguson, Marcio Diniz, Reza Mehrazin, Peter Wiklund, Alan Tan, Sumit Shah, Matthew D Galsky
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., University of Alabama, Birmingham, AL, USA., Natera Inc, Austin, TX, USA., Stanford University Medical Center, Stanford, CA, USA., Duke University, Durham, NC, USA., Rush University Medical Center, Chicago, IL, USA., UC San Diego Health, La Jolla, CA, USA., Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: .