What are the newer modalities of treatment for bladder cancer?

From the Guidelines

The most effective approach to treating bladder cancer involves a multimodal strategy, including immunotherapy, targeted therapies, and bladder-preservation techniques, as outlined in the latest guidelines and research, such as the NCCN Guidelines Insights: Bladder Cancer, Version 3.2024 1. The treatment of bladder cancer has undergone significant advancements in recent years, with a focus on personalized and effective options. Immunotherapy, particularly immune checkpoint inhibitors like pembrolizumab and atezolizumab, has emerged as a cornerstone treatment for metastatic urothelial carcinoma, enhancing the body's immune response against cancer cells 1. For patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), nadofaragene firadenovec, an intravesical gene therapy, offers a promising alternative by delivering the interferon alfa-2b gene to trigger local immune responses 1. Some key points to consider in the treatment of bladder cancer include:

• The use of antibody-drug conjugates like enfortumab vedotin for locally advanced or metastatic disease, which target cancer cells with cytotoxic agents 1
• Targeted therapies addressing specific genetic alterations, such as erdafitinib for FGFR alterations, provide personalized treatment options 1
• Enhanced bladder-preservation approaches combining maximal transurethral resection with chemoradiation, allowing suitable patients to avoid radical cystectomy while maintaining quality of life 1 These newer modalities represent significant progress in bladder cancer management, offering more personalized, effective options with potentially fewer side effects than traditional approaches, though patient selection and multidisciplinary evaluation remain crucial for optimal outcomes 1.

From the FDA Drug Label

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma: who are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. Cisplatin Injection is indicated as a single agent for patients with transitional cell bladder cancer which is no longer amenable to local treatments, such as surgery and/or radiotherapy.

The newer modalities of treatment for bladder cancers include immunotherapy with pembrolizumab (KEYTRUDA) and chemotherapy with cisplatin.

• Pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma, as well as for patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) 2.
• Cisplatin is indicated as a single agent for patients with transitional cell bladder cancer that is no longer amenable to local treatments 3. Key words: bladder cancer, pembrolizumab, cisplatin, immunotherapy, chemotherapy.

From the Research

Newer Modalities of Treatment for Bladder Cancers

• The treatment landscape for non-muscle invasive bladder cancer (NMIBC) is evolving, with a focus on novel therapies to address the limitations of current treatments, such as intravesical Bacille Calmette-Guérin (BCG) and chemotherapy 4, 5.
• Immunotherapy has emerged as a promising approach, with agents like pembrolizumab, an anti-programmed cell death (PD)-1 antibody, showing efficacy in BCG-unresponsive, high-risk disease 4, 6.
• Other novel immunotherapies being explored include checkpoint inhibitors, toll-like receptor agonists, and recombinant viral vectors, which may provide better options for managing NMIBC 5, 6.
• New mechanisms of drug delivery are also being investigated, such as the use of the GemRIS (TAR-200) device and delivery of intravesical chemotherapy at higher temperatures 4, 7.
• The role of urologists in the management of NMIBC is expected to evolve and expand with the development of these novel therapies 4.

Current Status and Future Directions

• The current treatment options for NMIBC are limited, and there is a need for novel approaches to reduce the treatment burden and improve outcomes for patients 8, 6.
• Immunotherapy has shown promise in the treatment of high-grade NMIBC and BCG-unresponsive disease, and several clinical trials are ongoing to evaluate its efficacy 6.
• The development of reliable biomarkers for response to immunotherapy is crucial to further select patients who may benefit from these therapies 6.
• The treatment landscape for NMIBC is rapidly changing, with a focus on personalized medicine and the development of novel therapies tailored to individual patient needs 7.

Novel Therapies and Treatment Approaches

• Several novel therapies are being explored for the treatment of NMIBC, including viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines 6.
• New surgical techniques, alterations in dwell time for intravesical therapy, and changes in the delivery method and schedule of intravesical therapies are also being investigated 7.
• Systemic therapies, especially immunotherapy, are being evaluated for their potential to improve outcomes for patients with NMIBC 7.