Study findings presented at the ASCO Annual Meeting provide proof of concept that cell–free DNA methylation may be used as a predictive biomarker of response to neoadjuvant chemotherapy for patients with muscle–invasive bladder cancer in the SWOG S1314 study.

“Neoadjuvant chemotherapy is the standard of care in muscle-invasive bladder cancer patients. However, treatment is intense, the overall benefit is small, and there is no established marker to identify patients who benefit most,” wrote Yi-Tsung Lu, MD, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, and colleagues.

This study aimed to evaluate cell–free DNA methylation in relation to pathologic response among patients with muscle–invasive bladder cancer in the SWOG S1314 study.

Researchers used blood samples collected prospectively from patients before and during standard neoadjuvant chemotherapy. Pathologic response was documented at the time of radical cystecytomy. Researchers then analyzed differential methylation between pathologic responders and non–responders.

From the prechemotherapy plasma cell-free DNA, researchers developed a methylation–based response score (mR-score) to predict pathologic response. This score can also be calculated from plasma samples collected after the first cycles of neoadjuvant chemotherapy.

Dr Lu and colleagues also stated that using cell–free DNA methylation data to calculate circulating bladder DNA fraction “had a modest but independent predictive ability for treatment response.” By combining the two methods (mR-score and circulating bladder DNA fraction) the researchers were able to predict pathologic response outcomes in 79% of patients from plasma collected before chemotherapy and after 1 cycle of treatment.

“Our study provides proof of concept that [cell–free] DNA methylation may be used to predict treatment response in bladder cancer patients receiving neoadjuvant chemotherapy,” concluded Dr Lu and colleagues.

Source:

Lu Y, Plets M, Morrison G, et al. Cell-free DNA methylation as a predictive biomarker of response to neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer in SWOG S1314. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL. Abstract 4506.