Molecular Markers

At the session, Dr Black discussed the future of molecular markers and how they can help clinicians to identify appropriate patients for neoadjuvant chemotherapy.

“There is a strong minority of clinicians in the United States who believe that only higher-risk patients should get neoadjuvant chemotherapy, while lower-risk patients are better off moving ahead with surgery,” Dr Black explained. “There is a lot of work being done with molecular markers to identify patients that are most likely to respond.”

According to Dr Black, there are 3 areas of research into molecular markers that look compelling for MIBC. The first is the COXEN (co-expression extrapolation) model, which uses molecular profiles to translate drug sensitivities seen in one set of cancers to make predictions for another independent set of cell lines or human tumors.5

“We take a patient’s tumor prior to treatment, biopsy the tissue, and do gene expression profiling,” Dr Black said. “We look at the RNA and match the gene expression signatures to known signatures of response. That way you can profile the patient’s tumor and decide if there is a high likelihood of response, and, if there is not, skip chemotherapy.”

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The COXEN model has only been tested retrospectively, Dr Black said, but there is an ongoing prospective trial that recently finished enrollment (ClinicalTrials.gov Identifier: NCT02177695).6

The second promising use of markers is also based on gene expression. Dr Black and colleagues recently validated that those patients with the basal bladder cancer subtype — as opposed to the luminal — seemed to have the biggest benefit from chemotherapy, while other subtypes had little benefit.7

“If validated, patients with basal should get chemotherapy followed by surgery and everybody else should get surgery upfront,” Dr Black said.