Extended Follow-up of a Response-Guided Bladder-Sparing Treatment Approach for Muscle-Invasive Bladder Cancer and Monitoring of Plasma and Urine Tumor DNA

Neoadjuvant systemic therapy yields pathological complete responses in some patients with muscle-invasive bladder cancer (MIBC), suggesting select patients may avoid cystectomy. We previously reported the results of the HCRN GU16-257 trial exploring a response-guided approach to MIBC in which patients achieving a clinical complete response (cCR) after gemcitabine, cisplatin, and nivolumab could forgo cystectomy. Here we report long-term follow-up and explore circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) to refine future patient selection. At 47-months median follow-up, cCR status was prognostic for metastasis-free and overall survival. Three-year bladder-intact survival among cCR patients was 69%. Undetectable baseline ctDNA was associated with exceptionally low metastatic risk. Among non-cCR patients, undetectable ctDNA at restaging (prior to definitive local therapy) was associated with better metastasis-free survival. Detectable utDNA in cCR patients was associated with inferior bladder-intact survival. These findings establish a framework for incorporating ctDNA and utDNA into response-guided bladder-sparing paradigms.

• Type: Other
• Archive: European Genome-phenome Archive (EGA)