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 ¹, Arnab Basu ², George Laliotis ³

⁰Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

European Urology Oncology +

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July 16, 2024

View abstract on PubMed

Summary

Circulating tumor DNA (ctDNA) testing after bladder cancer surgery can predict recurrence. Undetectable ctDNA suggests patients may not benefit from adjuvant therapy, aiding treatment decisions.

Area Of Science

Oncology
Molecular Diagnostics
Genomics

Background

Muscle-invasive bladder cancer (MIBC) carries a high risk of recurrence post-radical cystectomy (RC).
Accurate biomarkers are crucial for prognostication and guiding perioperative systemic therapies.
Tumor-informed circulating tumor DNA (ctDNA) analysis offers a potential solution.

Purpose Of The Study

To evaluate the prognostic and predictive capabilities of tumor-informed ctDNA testing.
To assess ctDNA's association with recurrence in MIBC patients undergoing RC.
To determine if ctDNA status can inform adjuvant therapy decisions.

Main Methods

Retrospective analysis of real-world data from 167 MIBC patients undergoing RC.
Utilized a commercial ctDNA test (Signatera) on 852 plasma samples.
Assessed ctDNA status pre-RC, during molecular residual disease (MRD) monitoring, and surveillance windows.
Employed Cox regression analysis to correlate ctDNA status with recurrence and disease-free survival (DFS).

Main Results

Detectable ctDNA post-surgery was significantly associated with shorter DFS (MRD: HR 6.93; surveillance: HR 23.02; p < 0.001).
Pre-RC, MRD, and surveillance ctDNA detection were independent predictors of shorter DFS.
Patients with undetectable ctDNA did not show a significant benefit from adjuvant therapy (p = 0.34).

Conclusions

Tumor-informed ctDNA testing is prognostic and potentially predictive in MIBC patients post-RC.
ctDNA status can identify high-risk patients, aiding in personalized treatment strategies.
This approach may refine patient counseling and treatment decision-making for bladder cancer.

Keywords:

Biomarkers Bladder cancer Circulating tumor DNA Muscle-invasive bladder cancer Radical cystectomy Recurrence