Protocol for Retrospective Analysis of Circulating and Urine Tumor DNA Biomarkers in HCRN GU16-257: A Phase 2 Trial of Gemcitabine, Cisplatin, and Nivolumab with Selective Bladder Sparing in Muscle-Invasive Bladder Cancer v1

HCRN GU16-257 was a prospective phase 2 trial evaluating gemcitabine, cisplatin, and nivolumab as organ-sparing treatment for muscle-invasive bladder cancer (MIBC). The trial enrolled 76 patients with cisplatin-eligible cT2-T4aN0M0 urothelial bladder cancer who received four cycles of treatment followed by clinical restaging. Patients achieving a clinical complete response (cCR) were offered the option to proceed without cystectomy and receive eight additional doses of nivolumab. Circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) represent promising biomarkers for monitoring treatment response, predicting outcomes, and guiding therapeutic decisions in bladder cancer. This retrospective analysis aims to evaluate the prognostic and predictive value of these liquid biopsy biomarkers within the context of the organ-sparing treatment paradigm.