Mehdi Adhami contributes an article on newer bladder cancer treatments and how they work.
Novel intravesical (“in-bladder”) therapies for non-muscle-invasive bladder cancer (NMIBC) refractory to conventional therapies
Introduction
Non-muscle-invasive bladder cancer (NMIBC) is a form of bladder cancer that remains within the bladder lining and has not invaded deeper tissues. Standard treatments, such as intravesical (“in-bladder”) Bacillus Calmette-Guérin (BCG) (a live attenuated bacteria) or chemotherapy, are usually effective. However, these treatments may fail to control the disease for some patients.
After ensuring adequate delivery of conventional therapies, the urologist may recommend cystectomy (removal of the bladder) as the next step for refractory cases, depending on patient circumstances. Novel therapies may be considered for those who are unable to undergo surgery or prefer bladder-preserving options. Many of these therapies are still experimental, and their long-term effectiveness is unclear. Some therapies may only be offered at specific centres or within clinical trials (requiring meeting strict eligibility criteria), and some are still not available in Australia.
Agents with multiple studies supporting their use (still experimental)
Second-agent intravesical chemotherapy
What it is: When first-line chemotherapy or BCG fails, alternative drugs may be administered to the bladder. These agents work by damaging the DNA of cancer cells. This prevents the cancer cells from dividing and growing.
Examples: Gemcitabine, docetaxel.
Combination intravesical chemotherapy
What it is: Two or more chemotherapy drugs are combined to enhance effectiveness. This may improve outcomes in cases unresponsive to single-agent chemotherapy.
Examples: Gemcitabine with mitomycin or gemcitabine with docetaxel.
Combination immunotherapy
What it is: Different immunotherapeutic agents are combined to enhance the immune response to target cancer cells.
Examples: BCG combined with interferon.
Immune checkpoint inhibitors
What it is: Drugs that block the “brakes” on the immune system, allowing the body’s immune cells to attack the tumour. They can be administered into the bladder or systemically (intravenously).
Examples: Pembrolizumab
Hyperthermic intravesical chemotherapy (HIVEC)
What it is: Heated chemotherapy agents are delivered into the bladder to enhance their effectiveness and penetration.
Examples: Heated Mitomycin C
Highly experimental therapies (in the developmental stage, minimal evidence)
Nanotechnology-based drug delivery
What it is: Nanoparticles are used to deliver drugs directly to cancer cells in the bladder, improving retention and targeting. This enhances drug absorption and effectiveness while reducing side effects.
Examples: ABI-009 (nab-rapamycin)
Targeted therapies
What it is: Drugs that specifically target molecules or pathways critical for cancer growth.
Examples: Antibody-drug conjugates or inhibitors of specific tumour markers.
Emerging immunotherapeutic agents
What it is: Drugs that promote tumour control by enhancing the immune response or directly targeting cancer cells.
Examples: oncolytic adenoviruses, vaccine therapy, recombinant fusion protein and gene therapy
Mehdi Adhami is a Urology Research Fellow at Icon Cancer Centre and Monash University School of Translational Medicine. He volunteers with YURO and is a board member of BladderCancer.org.au