Clinical Advances in Muscle Invasive Bladder Cancer

The discussion begins with KEYNOTE-905/EV-303 in cisplatin-ineligible muscle-invasive bladder cancer, where perioperative enfortumab vedotin plus pembrolizumab demonstrated improvements in event-free and overall survival. This is followed by KEYNOTE-B15, which compares perioperative EVP with gemcitabine/cisplatin and identifies EVP as the first non-platinum regimen to outperform cisplatin-based therapy. Implications for clinical adoption are considered, including the potential for EVP to extend across cisplatin eligibility groups, unresolved questions regarding perioperative duration and adjuvant use, and the need to avoid premature de-escalation outside of trial settings.

The latter portion of the episode focuses on biomarker-driven decision-making. Data from RETAIN-2 highlight the prognostic value of post-neoadjuvant ctDNA positivity for systemic relapse risk, while underscoring its limitations in detecting intravesical recurrence. Complementary findings from NIAGARA suggest that urine tumor DNA may more accurately reflect local disease burden and pathologic complete response. Together, these studies frame an evolving role for circulating and urine-based biomarkers in guiding surveillance, treatment selection, and timing—central considerations in maintaining the curative window.