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Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
K M Patel1,2,3, K E van der Vos4, C G Smith1,2
1Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Scientific Reports
|July 19, 2017
Summary
Detecting mutant DNA in body fluids can non-invasively identify muscle-invasive bladder cancer (MIBC) treatment failure. Persistent mutant DNA during neoadjuvant chemotherapy (NAC) accurately predicts disease recurrence, offering a promising biomarker.
Area of Science:
- Oncology
- Genetics
- Biomarkers
Background:
- Muscle-invasive bladder cancer (MIBC) presents a significant clinical challenge with limited treatment response.
- Neoadjuvant chemotherapy (NAC) offers a survival benefit for some MIBC patients, but predicting response remains difficult.
Purpose of the Study:
- To investigate the utility of circulating tumor DNA (ctDNA) in body fluids as a non-invasive biomarker for predicting NAC response in MIBC.
- To assess the potential of mutant DNA (mutDNA) levels and dynamics to track tumor evolution and predict treatment outcomes.
Main Methods:
- Collection of 248 liquid biopsy samples (plasma, urine cell pellet, urine supernatant) from 17 MIBC patients undergoing NAC.
- Analysis of single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing.
- Longitudinal monitoring of mutDNA levels to assess tumor heterogeneity and treatment response.
Main Results:
- MutDNA was detected in plasma, urine cell pellet, and urine supernatant, with significantly higher levels in urine samples (p < 0.001).
- Longitudinal mutDNA analysis revealed tumor evolution under NAC pressure, tracking distinct clones with varying sensitivities.
- Persistent mutDNA detection during NAC was a significant predictor of disease recurrence (p = 0.003).
Conclusions:
- Urine-based liquid biopsies are a sensitive source of mutDNA for monitoring MIBC.
- Dynamic changes in mutDNA during NAC can reflect tumor evolution and heterogeneity.
- Persistent mutDNA during NAC is a strong early indicator of treatment failure and disease recurrence in MIBC.
