The Significance of KEYNOTE-905 in Muscle-Invasive Bladder Cancer

An expert discusses the KEYNOTE-905 trial, a landmark study in muscle-invasive bladder cancer (MIBC) that explored the use of immunotherapy in patients ineligible for cisplatin-based chemotherapy. The trial’s design was groundbreaking because it evaluated pembrolizumab, an immune checkpoint inhibitor, in both neoadjuvant (presurgery) and adjuvant (postsurgery) settings—a comprehensive perioperative approach rather than the traditional neoadjuvant-only model. By doing so, the study aimed to harness the full potential of immune activation before and after surgery to reduce recurrence risk and improve long-term survival outcomes. Its randomized, controlled framework and inclusion of cisplatin-ineligible patients filled a crucial gap in existing treatment paradigms, providing much-needed data for a population historically lacking effective systemic options.

The trial findings demonstrated significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rates with pembrolizumab compared with standard care. These results signify a major advance for patients unable to tolerate cisplatin, offering a new therapeutic avenue that meaningfully extends survival while potentially curing some patients before surgery. The improvements in pCR highlight the ability of pembrolizumab to eradicate microscopic disease early, whereas gains in EFS and OS confirm durable benefits extending beyond the surgical period. Collectively, these findings redefine the treatment landscape for MIBC, moving immunotherapy from a later-line or metastatic context into the curative-intent, perioperative setting.

From a design standpoint, incorporating both neoadjuvant and adjuvant therapy was a strategic decision that strengthens the trial’s clinical relevance. Although neoadjuvant therapy can prime the immune system and target circulating tumor cells, residual disease or micrometastases may persist post surgery. By extending pembrolizumab into the adjuvant phase, the study sought to maintain immune surveillance and prevent relapse. This holistic perioperative design thus offers a more complete and durable antitumor response, reflecting an evolution in cancer trial methodology toward integrated, long-term immune modulation.