What are the newer modalities of treatment for bladder (urinary bladder) cancer?

From the Guidelines

The most effective treatment modalities for bladder cancer include immunotherapy with checkpoint inhibitors, such as pembrolizumab and atezolizumab, which have revolutionized treatment for advanced and metastatic disease, offering durable responses with fewer side effects than traditional chemotherapy. Recent advances in bladder cancer treatment have expanded therapeutic options, including newer agents with improved toxicity profiles, such as immune checkpoint inhibitors, antibody-drug conjugates, and targeted therapies. For non-muscle invasive bladder cancer (NMIBC), intravesical BCG remains standard, but newer options include nadofaragene firadenovec gene therapy and erdafitinib for FGFR-altered tumors, as noted in the NCCN guidelines 1. Enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, has shown remarkable efficacy in previously treated advanced disease, as highlighted in the NCCN guidelines insights 1. Bladder-sparing trimodal therapy combining maximal TURBT with concurrent chemoradiation has improved organ preservation rates, and enhanced surgical techniques, including robot-assisted radical cystectomy, have reduced recovery time and complications, as discussed in the clinical evidence for the first-line treatment of advanced urothelial carcinoma 1. These newer treatments work through various mechanisms, including immunotherapies that restore T-cell function against cancer cells, targeted therapies that inhibit specific molecular pathways driving tumor growth, and antibody-drug conjugates that deliver cytotoxic agents directly to cancer cells, all representing significant improvements in bladder cancer management. Key considerations in treatment decision-making include the presence or absence of medical comorbidities, such as cardiac disease, autoimmune disease, peripheral neuropathy, diabetes, and renal dysfunction, as well as the risk classification of the patient based on disease extent, as outlined in the NCCN guidelines insights 1. Molecular/genomic testing is recommended to be conducted early, ideally at diagnosis of advanced bladder cancer, to facilitate treatment decision-making and to prevent delays in administering later lines of therapy, as noted in the NCCN guidelines insights 1. The mainstay of treatment for metastatic urothelial bladder cancer is systemic therapy, although palliative radiotherapy may be an option for some patients, as discussed in the clinical evidence for the first-line treatment of advanced urothelial carcinoma 1. Overall, the treatment landscape for advanced urothelial carcinoma is evolving, with emerging evidence from randomized controlled trials of IO agents suggesting that survival times exceeding 20 months are possible, as highlighted in the clinical evidence for the first-line treatment of advanced urothelial carcinoma 1.

From the FDA Drug Label

KEYTRUDA may be used with the medicine enfortumab vedotin in adults when your bladder or urinary tract cancer has spread or cannot be removed by surgery (advanced urothelial cancer) KEYTRUDA may be used alone when your bladder or urinary tract cancer: has spread or cannot be removed by surgery (advanced urothelial cancer), and you are not able to receive chemotherapy that contains platinum (medicines called either cisplatin or carboplatin), or you have received chemotherapy that contains platinum, and it did not work or is no longer working 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.

Newer modalities of treatment for bladder cancers include:

• Immunotherapy with KEYTRUDA (pembrolizumab), which may be used alone or in combination with other treatments for advanced urothelial cancer
• Combination therapy with enfortumab vedotin and KEYTRUDA for advanced urothelial cancer
• Chemotherapy with cisplatin as a single agent for patients with transitional cell bladder cancer that is no longer amenable to local treatments. 2 3

From the Research

Newer Modalities of Treatment for Bladder Cancers

• The treatment of bladder cancers has evolved with the introduction of newer modalities, including immunotherapy and targeted treatments 4, 5, 6, 7, 8.
• Neoadjuvant atezolizumab with gemcitabine and cisplatin has shown promising results in patients with muscle-invasive bladder cancer (MIBC), with a non-muscle-invasive downstaging rate of 69% 4.
• Pembrolizumab has also been shown to be effective in patients with MIBC, with improved event-free survival and pathologic response rates compared to cisplatin-based chemotherapy or upfront radical cystectomy 5.
• Immunotherapy with checkpoint inhibitors has become a well-established treatment option for patients with metastatic bladder carcinoma, with significant improvements in overall survival 6, 8.
• Other newer modalities of treatment, such as gene therapy, photodynamic therapy, and nanomedicine, are also being explored for the treatment of bladder cancers 7.

Comparison of Newer Modalities with Traditional Treatments

• Neoadjuvant pembrolizumab has been shown to be superior to cisplatin-based chemotherapy or upfront radical cystectomy in terms of event-free survival and pathologic response rates in patients with MIBC 5.
• Immunotherapy with checkpoint inhibitors has been shown to prolong overall survival in patients with metastatic bladder carcinoma, with a median overall survival of 15-17 months 8.
• The use of newer modalities, such as immunotherapy and targeted treatments, has the potential to improve the quality of life and reduce the morbidity associated with traditional treatments, such as radical cystectomy and chemotherapy 6, 7.

Future Directions

• Further studies are needed to fully evaluate the efficacy and safety of newer modalities of treatment for bladder cancers, including immunotherapy and targeted treatments 4, 5, 6, 7.
• The development of biomarkers to predict response to treatment and the identification of patients who are most likely to benefit from newer modalities of treatment are urgent needs in the field of bladder cancer research 6.