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Thomas Flaig, MD


ASCO 2022: Can Cell-Free DNA Methylation Predict Chemotherapy Benefit in Bladder Cancer?

By: Victoria Kuhr, BA
Posted: Friday, June 10, 2022

Yi-Tsung Lu, MD, of the University of Southern California (USC), Los Angeles, and colleagues proposed that cell-free DNA (cfDNA) methylation may be a predictive biomarker of response in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy. These findings were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4506).

“With further validation, this approach may help physicians assess whether a patient with muscle-invasive bladder cancer would benefit from receiving neoadjuvant chemotherapy prior to definitive radical cystectomy,” stated senior study author Amir Goldkorn, MD, also of USC, in a press release from the SWOG Cancer Research Network.

The study’s proof of concept is from a correlative study conducted within the SWOG S1314 clinical trial. The 237 patients enrolled in the study had metastatic muscle-invasive urothelial bladder cancer. All patients were treated with neoadjuvant chemotherapy.

This study collected blood samples from approximately 73 patients from the SWOG S1314 clinical trial before and during standard neoadjuvant chemotherapy. The investigators extracted cfDNA from those samples and profiled patterns of DNA methylation for each patient. The patients’ pathologic response was documented at radical cystectomy.

The study authors used these data to analyze the cfDNA methylation patterns to identify differences in methylation between patients whose tumors had responded to neoadjuvant chemotherapy and those whose tumors had not. From these measurements, they developed a methylation-based response score (mR-score) to predict whether a tumor would respond to neoadjuvant chemotherapy.

The study authors used a prechemotherapy plasma cfDNA to develop the mR-score. Alternatively, the mR-score can be calculated using plasma samples collected after the first cycle of neoadjuvant chemotherapy. This calculation resulted in predictions similar to those using prechemotherapy plasma cfDNA.

Furthermore, the study authors used cfDNA methylation data to calculate the circulating bladder DNA fraction. This calculation resulted in a “modest but independent predictive ability for treatment response.” After combining the mR-score and circulating bladder DNA fraction, the study authors successfully predicted the pathologic response outcomes in 79% of patients based on the plasma collected before chemotherapy and after one cycle of chemotherapy.

Disclosure: For full disclosures of the study authors, visit

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