Michael A. O’Donnell, MD, the Richard D. Williams Chaired Professor of Urology and director of urologic oncology at the University of Iowa, has received a two-year, $300,000 Research Innovation Award from the Bladder Cancer Advocacy Network (BCAN).

The award will support the development of a tool to help urologic oncologists create personalized treatment plans for patients with non-muscle invasive bladder cancer (NMIBC) who are being treated with one of an increasing number of chemotherapy regimens now available.

Working with researchers in Switzerland with expertise in cancer modeling and the data management and analysis that cancer modeling requires, O’Donnell’s team aims to develop an integrated molecular chemo response tool (IMCRT) that will analyze a patient’s tumor samples to determine the samples’ susceptibility to various chemotherapy drugs, monitor the genetic features of the patient’s tumor during chemo treatment to identify genetic markers associated with tumor killing, and analyze the patient’s urine to assess the effectiveness of the treatment by measuring the disappearance of tumor cells.

“Although I am a surgeon by training, my goal as a bladder cancer uro-oncologist has always been to save bladders whenever possible,” O’Donnell says. “The BCAN Research Innovation Award will allow me to leverage my more than 30 years of clinical experience coupled with state-of-the-art technology from my collaborators at the University of Bern, Switzerland, to fundamentally improve the chances for these patients with early bladder cancer to keep their bladders healthy and cancer-free.”

NMIBC is bladder cancer that has been discovered before the tumor cells have penetrated the deep bladder muscle. The cancer is usually treated by first scraping the tumor tissue out of the bladder and then administering medication intravesically (directly into the bladder) to destroy any remaining tumor cells and prevent the growth of new tumor cells.

Since the 1970s, the most frequently used medication for that purpose has been bacillus Calmette-Guérin (BCG), an immunotherapy derived from cow tuberculosis that has succeeded in about 60% of patients treated. When BCG didn’t succeed, the only option remaining was removal of the patient’s bladder.

In 2009, O’Donnell pioneered the use of a sequential doublet chemotherapy known as gem/doce, an alternative to BCG in which gemcitabine and docetaxel are instilled into the bladder sequentially. After determining that gem/doce could be an effective treatment in patients who had failed BCG, O’Donnell began using the regimen as a replacement for BCG, an especially important development because widespread shortages of BCG often left doctors with no viable alternatives.

Retrospective studies by O’Donnell and his team demonstrated that gem/doce had worked as well as, or better than, BCG in killing tumor cells, with fewer side effects. That discovery led to the development of more sequential doublet chemotherapy combinations, offering physicians an unprecedented number of choices for bladder salvage and creating the need for tools to help determine which of the regimens would be most appropriate for any given patient’s tumor cells.

The IMCRT is intended to benefit patients in multiple ways.

“Not only will it help tell us the best current treatment but it will also provide ‘next best’ choices in case the first choice can’t or shouldn’t be used due to adverse reactions or allergies,” O’Donnell says. “This tool also should provide the basis for developing future treatments based on identifying a wide range of actionable tumor-killing pathways per individual patient.”

In addition to O’Donnell, the team includes Kristina Thiel, PhD; Yi Luo, MD, PhD; and Mohamad Abou Chakra, MD, from the University of Iowa and Marianna Kruithof-de Julio, PhD; Bernard Kiss, MD; Panagiotis Chouvardas, PhD; and Marta De Menna, PhD, from the University of Bern.