849 Background: Trimodal therapy remains the standard organ-sparing approach for muscle-invasive bladder cancer (MIBC), yet its clinical benefits are limited, and noninvasive biomarkers to guide dynamic treatment decisions are currently unavailable. There is an urgent need for innovative therapeutic strategies and reliable biomarkers to improve outcomes in localized HER2-positive MIBC. Methods: In this proof-of-concept study, we evaluated the safety and efficacy of disitamab vedotin (RC48, a HER2-targeted antibody-drug conjugate) combined with toripalimab (JS001, anti-PD-1) and radiotherapy in six patients with localized HER2-positive MIBC (DECIDING-1 study, ClinicalTrials.gov: NCT05979740). Longitudinal liquid biopsy analyses were performed using the PredicineCARE assay to profile circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA), assessing their utility in monitoring treatment response and detecting relapse. Results: The combination therapy demonstrated a favorable safety profile, with no grade 4 treatment-related adverse events or deaths observed. Five patients (83.3%) achieved a complete response and remained recurrence-free during follow-up. Longitudinal biomarker analysis revealed that utDNA testing exhibited high accuracy in tracking therapeutic efficacy and enabled early detection of tumor recurrence, whereas ctDNA was largely undetectable in blood samples. Conclusions: This study establishes the feasibility and efficacy of a novel bladder-preserving regimen combining HER2-targeted therapy, immunotherapy, and radiotherapy for HER2-positive MIBC. DECIDING-II is recruiting for validation in a larger cohort. Furthermore, utDNA emerges as a promising noninvasive biomarker for real-time monitoring and early relapse detection. These findings support further investigation of this approach as a potential paradigm shift in MIBC management. Clinical trial information: NCT05979740 .
Zhang et al. (Sun,) studied this question.