A Review of Emerging Neoadjuvant Intravesical Strategies to Enhance Systemic Immune Checkpoint Blockade in Patients With Cisplatin-Ineligible Muscle-Invasive Bladder Cancer Through the Induction of Immunogenic Cell Death and Activation of Tertiary Lymphoid Structure formation
Patients diagnosed with muscle-invasive bladder cancer (MIBC) frequently exhibit a high incidence of micrometastatic disease. The current standard of care for localized MIBC involves cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. Novel treatment alternatives in the neoadjuv...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Korean Urological Oncology Society
2025-03-01
|
| Series: | Journal of Urologic Oncology |
| Subjects: | |
| Online Access: | http://www.e-juo.org/upload/pdf/juo-255000300015.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Patients diagnosed with muscle-invasive bladder cancer (MIBC) frequently exhibit a high incidence of micrometastatic disease. The current standard of care for localized MIBC involves cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. Novel treatment alternatives in the neoadjuvant setting are urgently needed because more than 50% of the patients are ineligible for standard cisplatinbased neoadjuvant chemotherapy. Neoadjuvant approaches for patients with cisplatin-ineligible MIBC are rapidly evolving, with significant advancements transforming the treatment landscape for MIBC. Recently, systemic immune checkpoint inhibitors (ICIs) have substantially improved neoadjuvant outcomes in this patient population. However, ICIs as standalone therapies provide durable effects in only a small subset of patients, with many ultimately developing drug resistance over time, adversely affecting the overall efficacy of ICI therapy. Combination strategies integrating various treatment modalities to modulate the highly immunosuppressive tumor microenvironment and enhancing the efficacy of ICI-mediated anticancer immunity are thus crucial to overcome resistance and improve the clinical applicability of ICIs. Incorporation of systemic ICIs into combination regimens with advanced intravesical therapies, such as TAR-200 and the oncolytic adenovirus CG0070, may offer safe and clinically effective treatment alternatives with the potential to transform the current standard of care for patients with cisplatin-ineligible MIBC. Several prospective studies that have investigated the combination of systemic ICIs with intravesical therapies, including innovative mechanisms of action, such as TAR-200 and oncolytic viruses, have provided preliminary data regarding their efficacy and safety. This review aims to summarize the mechanistic rationale and ongoing clinical trials involving novel neoadjuvant strategies combining intravesical TAR-200 or CG0070 with systemic ICIs for patients with cisplatin-ineligible MIBC, particularly focusing on the induction of immunogenic cell death and the development of tertiary lymphoid structures. |
|---|---|
| ISSN: | 2951-603X 2982-7043 |