OU College of Medicine Receives NCI-Prevent Grant for Bladder Cancer Chemoprevention

Researchers at OU Health Stephenson Cancer Center at the University of Oklahoma Health Sciences Center are using a $1 million grant from the National Cancer Institute to test a drug's effectiveness at stopping the progression of bladder cancer while it is in an early stage. The grant was awarded to Chinthalapally Rao, Ph.D., a professor of hematology-oncology in the OU College of Medicine, and Venkateshwar Madka, Ph.D., assistant professor of hematology-oncology.

Bladder cancer is the second-most common cancer of the genitourinary tract. In the United States, over 80,000 adults will be diagnosed with bladder cancer and a quarter of them will die from it. Men are at four-times the risk of bladder cancer than women, but women are more likely to die from it. The majority of cases of urothelial carcinoma of the bladder can be attributed to smoking and occupational and environmental carcinogen exposures.

Bladder cancer usually starts in the lining or inner layer of the bladder and as it grows through the layers of the bladder wall, it becomes more difficult to treat. The way bladder cancer is staged is based upon the depth of invasion into the bladder wall, with most bladder cancers considered to be non-muscle invasive (NMIBC) at diagnosis and approximately 25% of bladder cancers identified as muscle invasive (MIBC). MIBC has high mortality leading to death within two years of diagnosis if left untreated.

Intravesical instillation of Bacille Calmette-Guerin (BCG), a vaccine for tuberculosis, is the standard of care for NMIBC, along with chemotherapy regimens that include cisplatin or carboplatin. However, failure of these therapies in many patients and recent shortages of BCG have highlighted the necessity of novel therapeutic agents for treatment of NMIBC.

Rao and Madka are testing the FDA approved drug, apalutamide, as a possible preventative of bladder cancer in its early stages. Apalutamide, which is an FDA approved oral-drug for non-metastatic castration-resistant prostate cancer, works by inhibiting the binding of androgens to androgen receptors with a greater capacity than other anti-androgen agents.

The study will determine if apalutamide prevents progression of N-butyl-N nitrosamine (BBN) induced urinary bladder cancers in either early or middle stage carcinogenesis. If successful, apalutamide could provide a preventive strategy in NMIBC to mitigate progression to MIBC. Middle stage carcinogenesis is the stage where patients usually start to notice symptoms and it’s more difficult to treat.

“Bladder cancer can take several years to move from early lesions to the NMIBC stage and then to the MIBC stage. Since the majority of cases are diagnosed at NMIBC stage, if we can start intervention early, we may be able to stop it before it progresses to the chemotherapy stage,” said Madka.

Results of the study will determine the initiation of clinical trials in NMIBC patients for preventing the progression to MIBC.

“Preventing bladder cancer and its progression to invasive disease is a high priority — not only in Oklahoma, but across the country,” said Rao. “If apalutamide is found to treat early stage bladder cancer as anticipated, the fact that the drug is already FDA approved means that clinical trials can commence a lot sooner than if trialing a new drug or treatment. The difference is years and that can save lives.”