cfDNA May Aid Treatment Selection in MIBC

Cell-free DNA (cfDNA) methylation may be used to predict treatment response in patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant chemotherapy, according to an analysis of SWOG S1314 presented at the 2022 ASCO Annual Meeting (Abstract 4506).

Thomas Flaig, MD, of University of Colorado Cancer Center, presented the results. Dr. Flaig explained that although cisplatin-based neoadjuvant chemotherapy is the standard of care for patients with MIBC, the treatment is toxic to some patients. There has been ongoing work to identify predictive biomarkers to select, where patients would get the most benefit from this therapy.

In the study, Dr. Flaig and colleagues used blood samples from patients before and during standard neoadjuvant chemotherapy who were enrolled in the SWOG S1314 trial. Pathologic response was documented after radical cystectomy.

The researchers used pre-chemotherapy plasma cfDNA to develop a methylation-based response score (mR-score) predictive of pathologic response. They also used cfDNA methylation data to calculate the circulating bladder DNA fraction.

When these two things were combined, the researchers were able to successfully predict pathologic response outcomes in 79% of patients based on their plasma collected before chemotherapy and after 1 cycle of chemotherapy.

“Machine-learning can be applied to cfDNA methylomes to generate a biomarker signature which can be predictive of response to therapy,” Dr. Flaig said. “In this pilot study, the mR-score was not correlated with circulating bladder DNA fraction; hence, these two ‘independent’ markers may be used in conjunction to predict chemotherapy response.”

These methods need further validation in this setting, Dr. Flaig noted, but provide conceptual and technical proof of principle in a neoadjuvant cohort with a rapid response endpoint of plasma cfDNA methylation for response prediction, rather than detection.

He also noted that it has potentially greater applicability in the metastatic setting where there is high cfDNA and circulating tumor DNA as well.