HOW CTDNA AND UTDNA ARE RESHAPING TREATMENT PATHWAYS IN BLADDER CANCER: IMPLICATIONS FOR EARLY ACCESS, HEALTH TECHNOLOGY ASSESSMENT (HTA) AND REIMBURSEMENT
Author(s)
Mihaela Musat, PhD1, Anna Forsythe, MBA, MSc, PharmD2, Estella Mendelson, MBA, RN3, Saro Sarkisian, MD, MHA4.
1Oncoscope, Miami, FL, USA, 2Founder, Oncoscope-AI, Miami, FL, USA, 3Independent, East Hanover, NJ, USA, 4Frederick Health, Frederick, MD, USA.
1Oncoscope, Miami, FL, USA, 2Founder, Oncoscope-AI, Miami, FL, USA, 3Independent, East Hanover, NJ, USA, 4Frederick Health, Frederick, MD, USA.
OBJECTIVES: Circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) are minimally invasive biomarkers increasingly used to detect molecular residual disease and recurrence risk in bladder cancer. Recent studies suggest these biomarkers may move beyond prognostic assessment to guide treatment selection, escalation, and de-escalation strategies. As biomarker-guided treatment approaches emerge, continuous evidence monitoring becomes important for HTA, reimbursement, and clinical decision-making. We used a Real-Time AI-Assisted Living Systematic Literature Review (REAL-SLR) to characterize the evolving role of ctDNA and utDNA in muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC).
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was conducted in bladder cancer. Evidence from clinical trials, conference abstracts, publications, regulatory sources, and treatment guidelines was identified and structured. Studies were mapped according to clinical stage, treatment pathway, biomarker application, study design, and regulatory/guideline status.
RESULTS: As of June 18th 2026, the REAL-SLR included 553 bladder cancer studies, of which 24 evaluated ctDNA and/or utDNA as predictive (n=20) or treatment-guiding (n=4) biomarkers. IMvigor011 and TOMBOLA demonstrated improved outcomes with adjuvant atezolizumab following radical cystectomy in ctDNA-positive MIBC population. DECIDING-I evaluated ctDNA/utDNA for early relapse detection, while another study demonstrated immunotherapy de-escalation in very high-risk NMIBC patients achieving complete response and negative utDNA. ctDNA was more frequently associated with survival-related outcomes (14 studies), whereas utDNA more commonly predicted local bladder outcomes and pathological complete response (7 studies). Evidence suggests ctDNA better reflects systemic recurrence risk, while utDNA may be more sensitive for residual intravesical disease.
CONCLUSIONS: ctDNA and utDNA are evolving from prognostic biomarkers into tools that directly influence treatment selection, escalation, and de-escalation decisions in bladder cancer. This transition creates new biomarker-defined populations, treatment pathways, and comparator frameworks that may substantially affect future trial designs, HTA, reimbursement, and value-assessment processes. Living evidence approaches support identification of emerging evidence requirements and inform biomarker-driven treatment strategies.
METHODS: A PRISMA-compliant, continuously updated REAL-SLR was conducted in bladder cancer. Evidence from clinical trials, conference abstracts, publications, regulatory sources, and treatment guidelines was identified and structured. Studies were mapped according to clinical stage, treatment pathway, biomarker application, study design, and regulatory/guideline status.
RESULTS: As of June 18th 2026, the REAL-SLR included 553 bladder cancer studies, of which 24 evaluated ctDNA and/or utDNA as predictive (n=20) or treatment-guiding (n=4) biomarkers. IMvigor011 and TOMBOLA demonstrated improved outcomes with adjuvant atezolizumab following radical cystectomy in ctDNA-positive MIBC population. DECIDING-I evaluated ctDNA/utDNA for early relapse detection, while another study demonstrated immunotherapy de-escalation in very high-risk NMIBC patients achieving complete response and negative utDNA. ctDNA was more frequently associated with survival-related outcomes (14 studies), whereas utDNA more commonly predicted local bladder outcomes and pathological complete response (7 studies). Evidence suggests ctDNA better reflects systemic recurrence risk, while utDNA may be more sensitive for residual intravesical disease.
CONCLUSIONS: ctDNA and utDNA are evolving from prognostic biomarkers into tools that directly influence treatment selection, escalation, and de-escalation decisions in bladder cancer. This transition creates new biomarker-defined populations, treatment pathways, and comparator frameworks that may substantially affect future trial designs, HTA, reimbursement, and value-assessment processes. Living evidence approaches support identification of emerging evidence requirements and inform biomarker-driven treatment strategies.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HSD84
Topic
Health Service Delivery & Process of Care
Disease
Oncology