Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer

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 3rd; Marcio Diniz; Reza Mehrazin; Peter Wiklund; Alan Tan; Sumit Shah; Matthew D Galsky

doi:10.1016/j.euo.2024.07.001

Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer

Eur Urol Oncol. 2024 Jul 15:S2588-9311(24)00174-3. doi: 10.1016/j.euo.2024.07.001. Online ahead of print.

Authors

John P Sfakianos¹, Arnab Basu², George Laliotis³, Shivaram Cumarasamy¹, Jordan M Rich¹, Ajitha Kommalapati², Michael Glover⁴, Tamara Mahmood³, Neeraja Tillu¹, Christopher J Hoimes⁵, Grayce Selig⁵, Revathi Kollipara⁶, Tyler F Stewart⁷, Samuel Rivero-Hinojosa³, Punashi Dutta³, Mark Calhoun³, Shruti Sharma³, Meenakshi Malhotra³, Adam C ElNaggar³, Minetta C Liu³, James E Ferguson 3rd², Marcio Diniz⁸, Reza Mehrazin⁸, Peter Wiklund¹, Alan Tan⁶, Sumit Shah⁴, Matthew D Galsky⁹

Affiliations

¹ Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² University of Alabama, Birmingham, AL, USA.
³ Natera Inc, Austin, TX, USA.
⁴ Stanford University Medical Center, Stanford, CA, USA.
⁵ Duke University, Durham, NC, USA.
⁶ Rush University Medical Center, Chicago, IL, USA.
⁷ UC San Diego Health, La Jolla, CA, USA.
⁸ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: matthew.galsky@mssm.edu.

PMID: 39013741
DOI: 10.1016/j.euo.2024.07.001

Abstract

Background and objective: 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.

Methods: 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.

Results and limitations: 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.

Conclusions: 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.

Patient summary: 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.

Keywords: Biomarkers; Bladder cancer; Circulating tumor DNA; Muscle-invasive bladder cancer; Radical cystectomy; Recurrence.