Who should read this?
People with muscle-invasive bladder cancer (MIBC) who are not eligible for cisplatin chemotherapy, or who have declined it, and are considering treatment before and after surgery.
Which cancer is this about?
Muscle-invasive bladder cancer planned for radical cystectomy, in a cisplatin-ineligible or cisplatin-declining population.
Why this matters
For many years, people who could not receive cisplatin often had surgery alone, with limited proven systemic treatment options. KEYNOTE-905 tested a powerful combination given around the time of surgery to reduce recurrence and improve survival.
Treatment studied
The trial compared:
• Enfortumab vedotin + pembrolizumab before and after surgery versus
• Surgery alone
Results
Event-free survival:
Hazard ratio 0.40 (95% CI 0.28–0.57)
This represents about a 60% reduction in the risk of recurrence, progression, or death.
Overall survival:
Hazard ratio 0.50 (95% CI 0.33–0.74)
This represents about a 50% reduction in the risk of death at interim analysis.
Pathologic complete response:
57.1% with the combination vs 8.6% with surgery alone.
Regulatory note
Pembrolizumab plus enfortumab vedotin was approved by the FDA for peri-operative treatment of muscle-invasive bladder cancer in November 2025.
Key takeaway
For people with muscle-invasive bladder cancer who cannot receive cisplatin, peri-operative pembrolizumab plus enfortumab vedotin significantly reduces recurrence and improves survival compared with surgery alone.
This represents one of the most important advances for cisplatin-ineligible bladder cancer, but requires discussion about side effects, monitoring, and treatment timing around surgery.