Improving Quality of Life for Patients with Bladder Cancer

David Miyamoto, MD, PhD, and his colleagues at Massachusetts General Hospital are developing a liquid biopsy to personalize treatment for patients with muscle-invasive bladder cancer (MIBC). The innovative blood test will help identify which patients are good candidates for trimodality therapy (TMT), a combination of chemoradiotherapy and surgery to remove the tumor that preserves the bladder.The biomarker would also allow for non-invasive monitoring of treatment response during and after TMT.

Many patients with bladder cancer are treated with radical cystectomy, an invasive surgery to remove the entire bladder, but there are high rates of complications and significant impacts on quality of life. Recent research has shown that TMT and radical cystectomy have similar metastasis-free survival, cancer-specific survival and disease-free survival for select patients. However, 20% to 30% of patients initially treated with TMT experience disease recurrence and require surgery to remove the entire bladder.

“We need a better way to select patients who are most likely to benefit from TMT,” says Dr. Miyamoto. “Our team has developed a highly sensitive microfluidic chip technology that efficiently isolates circulating tumor cells (CTCs) that are shed from the cancer into the blood stream. Our innovative method enables sophisticated molecular profiling of tumors based on RNA expression in the CTCs.” In 2021, Dr. Miyamoto received a Biomarkers for Radiation Oncology Award from the Radiation Oncology Institute (ROI) – the ASTRO Foundation – to pursue this promising research. With the grant, Dr. Miyamoto’s team has made progress toward identifying unique pretreatment bladder CTC and tumor molecular signatures that predict clinical outcomes after chemoradiation therapy and developing a non-invasive test to detect the presence of bladder cancer cells in the blood to monitor minimal residual disease or early recurrence following TMT. They have published some of their findings to date in several journals, including Science Advances and Clinical Cancer Research.

Dr. Miyamoto used the results of the ROI-funded research to successfully compete for an R01 grant from the National Cancer Institute (R01CA259007) to continue the development of this new method of blood-based monitoring for patients with bladder cancer who are treated with TMT. “The grant from ROI provided critical support for our research at a time when we did not have funding to conduct the proposed project. Without this ROI award, it would not have been possible to generate the preliminary data necessary for the NIH R01 grant that we subsequently received to evaluate the liquid biopsy and molecular tissue biomarkers in larger cohorts of patients,” says Dr. Miyamoto. The team is currently conducting a clinical study to validate the ability of their CTC-based molecular assay to predict and monitor response to bladder-sparing TMT. They are also testing other liquid biopsies as alternative biomarkers and engaging in deep molecular profiling of CTCs from bladder cancer patients to elucidate mechanisms of resistance to chemoradiation and identify new potential therapeutic vulnerabilities.

Reliable and accurate molecular biomarkers to identify patients who are the best candidates for TMT could increase utilization of TMT and allow more patients to preserve their bladder, providing them with a better quality of life. The liquid biopsy that Dr. Miyamoto and his team are developing would be a practice-changing breakthrough that shows great promise to improve outcomes for patients with muscle-invasive bladder cancer.