Neoadjuvant Therapy in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer: Recent Progress, Challenges, and Future Directions in the Era of TAR-200 and Enfortumab Vedotin Plus Pembrolizumab - PubMed
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- #Neoadjuvant Therapy
- #Cisplatin-Ineligible
- #Muscle-Invasive Bladder Cancer
- Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is standard for cisplatin-eligible muscle-invasive bladder cancer (MIBC) patients.
- Many patients cannot receive cisplatin due to renal dysfunction, frailty, neuropathy, ototoxicity, or comorbidities, creating a need for cisplatin-free perioperative options.
- Neoadjuvant immune checkpoint inhibitors (ICIs) show promising pathologic complete response (pCR) rates in cisplatin-ineligible patients.
- Two emerging cisplatin-free paradigms: systemic intensification with enfortumab vedotin plus pembrolizumab (ADC plus PD-1 inhibitor) and bladder-centered intensification with TAR-200 (intravesical gemcitabine) plus systemic PD-1 blockade.
- Challenges include heterogeneous trial populations, endpoints, and limitations of cross-trial comparisons.
- Future directions include response-adapted strategies using circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA).
- Liquid biopsies may help identify patients needing additional treatment post-surgery and those who can avoid extra side effects.
- Future studies need to compare systemic and bladder-centered strategies to determine optimal treatment sequencing.