Bacillus Calmette-Guérin (BCG) remains the standard of care for non-muscle invasive bladder cancer. However, recurrent or progressive disease develops in 30 to 50 percent of patients who receive BCG.
“There is a treatment space we desperately need to fill for these patients who are BCG unresponsive or BCG refractory or relapsing,” said Gary D. Steinberg, MD, the Bruce and Beth White Family Professor and Director of Urologic Oncology at the University of Chicago Medical Center. “We all see patients who don’t respond to BCG. The good news is that there are a number of innovative approaches that are being developed and tested for our patients.”
Dr. Steinberg and three other experts will review several complex bladder cancer cases during Tuesday morning’s Plenary I program. They will examine alternatives to BCG and discuss future treatments being developed. The 30-minute discussion, titled Bladder Cancer: High Grade Superficial TCCA When There is No BCG or BCG Fails, will begin at 9:55 a.m. in Hall A in the San Diego Convention Center.
“We need to start by defining what we mean when we say BCG is no longer working for these patients,” Dr. Steinberg said. “Not all BCG is the same. Not all vials have the same mutational abnormalities. While BCG is a non-specific immune stimulation, in a perfect world, it would have some bladder cancer specific antigens so you could have some bladder cancer specific immune stimulation.”
When BCG fails, radical cystectomy is the current standard of care, but bladder cancer is a disease of the elderly and aging. Radical cystectomy has a mortality rate of 2 to 3 percent, but morbidity is significant, even with recent advances in perioperative care. When BCG fails, clinicians need non-surgical alternatives.
Intravesical chemotherapy has been tried, with generally disappointing results. Mitomycin C, gemcitibine, doxorubicin, docetaxel and paclitaxel are among the many agents that have produced less than stellar results.
“We know that bladder cancer is a very heterogeneous disease, a very heavily mutated disease,” Dr. Steinberg said. “So it makes sense that no one drug would cure all bladder cancers. When so many agents fail, it suggests that the ways we are giving intravascular chemotherapy is not too effective.”
Academic and commercial researchers are exploring multiple strategies. One possibility is electromotive current to increase drug penetration into the mucosa and tumor cells. Nanoparticle delivery of paclitaxel and other agents is also under investigation. At least one company is developing an implantable silicone tube that can be inserted into the bladder to provide controlled release of chemotherapy. Other research projects include hyperthermia using microwave energy focused on the bladder wall.
Immunotherapies are another active research area. Several companies are working on adenovirus-based vaccines that have been engineered to deliver a toxic payload. One strategy is to introduce genes programmed for tumor death. Another is to create a fusion protein that targets tumor cells to selectively deliver an endotoxin or other drug payload directly into target cells without affecting non-malignant cells.
Other vaccines are designed to stimulate the immune system to better attack bladder cancer. But some bladder cancers appear to be able to turn off the immune system in order to promote their own growth and survival. One of the newest vaccine strategies is to include a checkpoint inhibitor that blocks the turnoff signal to enhance immune system action.
Another strategy is to enhance implementation of existing BCG guidelines to achieve better outcomes.
“The ways we treat non-muscle invasive bladder cancer are all over the place,” Dr. Steinberg said. “What happens in academic medical centers is not what happens in the community. We have to better define and better implement treatment algorithms, better define the parameters of BCG use and BCG failure. And most importantly, we have to identify novel agents and mechanisms of actions for patients who do not respond to BCG.”
Plenary I Preview
Bladder Cancer: High Grade Superficial Transitional Cell Carcinoma When There is No BCG or BCG Fails
Presenter: Gary D. Steinberg, MD
9:55 – 10:25 a.m. Tuesday
Hall A, San Diego Convention Center