Revealing the Invisible: Circulating and Urinary Tumor DNA in Bladder Cancer
- 1Krantz Family Center for Cancer Research, Mass General Brigham Cancer Institute, Charlestown, MA 02129, USA
- 2Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- 3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Abstract
Muscle-invasive bladder cancer (MIBC) carries a high risk of recurrence and metastatic progression despite aggressive treatment with radical cystectomy or trimodality therapy. Current surveillance methods, including imaging and cystoscopy, have limited sensitivity for detecting molecular residual disease (MRD) and early recurrence, highlighting the need for reliable biomarkers to guide treatment selection. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that can provide real-time insights into tumor burden, treatment response, and recurrence risk. In this narrative review, we synthesize evidence on ctDNA’s potential in monitoring and guiding MIBC treatment. We discuss ctDNA detection methods and applications in genomic profiling, perioperative risk stratification, MRD detection, treatment selection, response monitoring, and post-treatment surveillance. Postoperative ctDNA positivity has been associated with significantly shorter disease-free survival (HR 6.93, 95% CI 2.40–20.05), and patients who failed to achieve ctDNA clearance during neoadjuvant chemotherapy had worse recurrence-free survival (HR 4.7, 95% CI 1.2–18.8). With further prospective validation, serial ctDNA monitoring may enable earlier detection of molecular recurrence and inform the timing and use of adjuvant therapy. The recent FDA approval of adjuvant atezolizumab for MIBC patients with ctDNA-detected MRD following cystectomy marks an important milestone in ctDNA-guided treatment selection. Given ctDNA’s limited sensitivity in detecting localized bladder recurrence, urinary tumor DNA (utDNA) may serve as a complementary biomarker to detect intravesical disease. Broader clinical implementation of these liquid biopsy strategies will require further validation, standardization, and efforts to reduce false-positive and false-negative results.
Related
- Evaluation of Urinary Circulating Tumor DNA to Detect Minimal Residual Disease in Patients with High-Risk Non-Muscle Invasive Bladder Cancer
- Urinary dual-site proenkephalin (PENK) methylation testing for detection of high-grade or invasive recurrence during surveillance of non-muscle-invasive bladder cancer
- Urinary Extracellular Vesicle–Associated EphA2 Predicts Intravesical Recurrence in Bladder Cancer
- Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.
- Serial urinary NGAL and CK20 for dynamic cardiovascular risk stratification in non-muscle-invasive bladder cancer: a retrospective clinical cohort study
BibTeX
@article{qin2026revealing,
title = {{Revealing the Invisible: Circulating and Urinary Tumor DNA in Bladder Cancer}},
author = {Sophia L. Qin and Benista Owusu-Amo and David T. Miyamoto},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213566},
url = {https://www.mdpi.com/2072-6694/18/21/3566},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Revealing the Invisible: Circulating and Urinary Tumor DNA in Bladder Cancer
AU - Sophia L. Qin
AU - Benista Owusu-Amo
AU - David T. Miyamoto
PY - 2026
DA - 2026/11/06
JO - Cancers
DO - 10.3390/cancers18213566
UR - https://www.mdpi.com/2072-6694/18/21/3566
AB - Muscle-invasive bladder cancer (MIBC) carries a high risk of recurrence and metastatic progression despite aggressive treatment with radical cystectomy or trimodality therapy. Current surveillance methods, including imaging and cystoscopy, have limited sensitivity for detecting molecular residual disease (MRD) and early recurrence, highlighting the need for reliable biomarkers to guide treatment selection. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that can provide real-time insights into tumor burden, treatment response, and recurrence risk. In this narrative review, we synthesize evidence on ctDNA’s potential in monitoring and guiding MIBC treatment. We discuss ctDNA detection methods and applications in genomic profiling, perioperative risk stratification, MRD detection, treatment selection, response monitoring, and post-treatment surveillance. Postoperative ctDNA positivity has been associated with significantly shorter disease-free survival (HR 6.93, 95% CI 2.40–20.05), and patients who failed to achieve ctDNA clearance during neoadjuvant chemotherapy had worse recurrence-free survival (HR 4.7, 95% CI 1.2–18.8). With further prospective validation, serial ctDNA monitoring may enable earlier detection of molecular recurrence and inform the timing and use of adjuvant therapy. The recent FDA approval of adjuvant atezolizumab for MIBC patients with ctDNA-detected MRD following cystectomy marks an important milestone in ctDNA-guided treatment selection. Given ctDNA’s limited sensitivity in detecting localized bladder recurrence, urinary tumor DNA (utDNA) may serve as a complementary biomarker to detect intravesical disease. Broader clinical implementation of these liquid biopsy strategies will require further validation, standardization, and efforts to reduce false-positive and false-negative results.
SN - 2072-6694
ER -