Bladder cancer is the tenth most common cancer worldwide, with more than half a million new cases and over 200,000 deaths from the disease in 2020. While the bladder is in many ways simpler than other organs, bladder cancer has evaded effective treatments for decades. Traditional therapies have been associated with local and systemic toxicities; for most patients who work through these side effects, many interventions may ultimately stop working. These limitations, coupled with a significant need for innovation in this space, have left the door wide open for scientific advances that address unmet needs in bladder cancer. Fortunately, significant strides have been made in the battle against this formidable disease.
Below are some key challenges posed by bladder cancer and its current treatment paradigms, as well as the innovative solutions that are enabling better, more durable options for patients living with bladder cancer.
Challenges with systemic therapies
Many patients with bladder cancer tend to be older and frailer and often cannot tolerate the toxicities associated with systemic treatments. Advanced age is the single greatest risk factor for bladder cancer, and diagnosis on average occurs between the ages of 70 and 84. The development of bladder cancer therapeutics has therefore become more focused on treatments that are appropriate for the patients who are most often affected by the disease. Given these challenges, localized approaches to organ-confined disease may enable better access to potentially curative therapies.
The bladder poses unique treatment challenges
Whether administered systemically or locally, drugs aimed at treating tumors within the bladder have been limited by an inability to deliver sufficient doses to the right place for a long enough period to result in a clinically meaningful impact. These drugs, for instance, suffer from low bioavailability and limited dwell times and do not distribute in a uniform fashion across the bladder. The efficiency with which the bladder eliminates substances further contributes to these challenges. Therapies aimed at mitigating regular bladder voiding cycles have required frequent dosing and regimens that may lead to poor patient compliance. Innovative technologies are now being developed to avoid the need for repetitive dosing by adequately maintaining effective doses within the bladder for weeks to months at a time.
Conventional therapies have limitations, especially in localized disease
Intravesical therapy is the established approach for the treatment of non-muscle invasive bladder cancer (NMIBC), which represents 70% of diagnosed cases of organ-confined disease. Bacillus Calmette-Guerin (BCG) has been the preferred therapy for high-risk NMIBC for decades, with little innovation since its approval in the early 1990s. In cases where BCG is effective and tolerated, maintenance regimens are recommended for up to 3 years. In up to 50% of cases, patients may ultimately become unresponsive to BCG, and in those who enjoy a durable response to therapy, global BCG supply shortages continue to disrupt reliable access to this important drug. These limitations highlight the significant and urgent need for new therapeutic options for those with NMIBC.
Novel approaches are also needed for muscle invasive bladder cancer (MIBC). The more aggressive treatments used for the 30% of organ-confined bladder cancer that is muscle invasive at diagnosis are associated with low patient tolerability and adherence, suggesting a consistent need for treatments that are less invasive for patients. While new therapies are being developed for NMIBC, we have recently witnessed more advances in the therapeutic landscape for muscle invasive and more advanced bladder cancer, which now includes options such as immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted therapies.
Recent innovations seek to transform the future of bladder cancer therapy
As science continues to inform our understanding of the biology and genetics underlying bladder cancer, we are seeing improvements in the way bladder cancer is diagnosed and treated. Immune checkpoint inhibitors have transformed bladder cancer treatment, and research is currently underway to determine if ICIs may be beneficial in earlier stages of disease. The ability to provide sustained tumor exposure via localized drug delivery is also supporting treatment in earlier disease settings in both NMIBC and MIBC and facilitating the development of synergistic drug combinations.
Going forward, we should focus on unmet needs and tailoring therapy
Bladder cancer treatments can attack not only tumors, but normal bladder tissue as well, which significantly impacts a patient’s quality of life. Targeted therapies with limited toxicity could lead to better tolerated bladder preservation treatment algorithms. As we continue to innovate in bladder cancer, we should consider the ongoing unmet needs of specific patient populations, including the need for multi-modal regimens to eliminate bladder cancer, therapies that spare or preserve the bladder, new actionable targets, and novel treatments for patients with low- and intermediate-risk NMIBC.
We will redouble our efforts to develop technologies that can deliver drugs to the bladder in ways that maximize intracellular potency, avoid unwanted side effects, and are administered by means that improve patient compliance and satisfaction, ultimately optimizing care for each and every bladder cancer patient around the world.