Implementing a personalized medicine approach in oncology increasingly includes the use of measurable residual disease (MRD) testing to detect molecular evidence of cancer that remains after treatment, enabling more precise risk stratification, earlier intervention, and more informed treatment management decisions. In colorectal and bladder cancers, a growing body of evidence demonstrates that MRD status can accurately identify patients at substantially higher risk of recurrence, often before disease becomes clinically or radiographically apparent. Emerging data further suggest that MRD testing may help guide adjuvant treatment decisions by identifying patients most likely to benefit from additional therapy while sparing lower-risk patients from unnecessary treatment and associated toxicities.
Daryl E. Pritchard, PhD
Despite this promise, integration of MRD testing into routine clinical care remains inconsistent, and patient access varies considerably across practice settings because of evidentiary, operational, and reimbursement-related challenges. In colorectal and bladder cancers, where recurrence rates remain substantial even after curative-intent treatment, MRD testing offers patients the opportunity for more personalized and vigilant posttreatment surveillance, enabling earlier detection of recurrence, reducing uncertainty and anxiety surrounding disease status, and potentially improving long-term outcomes through more timely clinical intervention. Failure to ensure appropriate access to MRD testing may contribute to delayed detection of recurrence, suboptimal treatment selection, and avoidable downstream health-care costs associated with recurrent and progressive disease. As evidence supporting the clinical utility of MRD testing continues to evolve, a clear understanding of its demonstrated value in colorectal and bladder cancers is important to help inform clinical practice, coverage policy, and patient access decisions.
ctDNA-Based MRD Testing in Colorectal Cancer
In colorectal cancer, the current surveillance recommendations include frequent blood biomarker testing (carcinoembryonic antigen [CEA]), imaging, and endoscopy procedures. In traditional practice, a cascade of endoscopy and CT scans follows elevated non-MRD blood biomarkers, which are known to be imprecise with false-positive rates up to 30%.1 A more precise biomarker for recurrence is needed to avoid costly downstream evaluations and anxiety associated with false-positive results. The current body of evidence supporting MRD testing following curative-intent surgery for colorectal cancer demonstrates substantial clinical value in identifying patients at highest risk of recurrence, improving prognostic risk stratification, and informing shared treatment decision-making regarding adjuvant therapy and surveillance strategies. Multiple prospective and retrospective studies have shown that circulating tumor DNA (ctDNA)-based MRD detection after surgery is among the strongest independent predictors of recurrence, frequently outperforming conventional clinicopathologic risk factors.2-8
ctDNA has been shown to have a higher sensitivity and specificity than the current blood biomarkers for recurrence (CEA) in clinical study settings. Postoperative ctDNA positivity consistently identifies patients with a markedly elevated likelihood of relapse, whereas ctDNA-negative patients experience substantially improved recurrence-free survival and overall prognosis. Importantly, the randomized DYNAMIC trial demonstrated that a ctDNA-guided approach to adjuvant therapy in stage II colon cancer reduced chemotherapy utilization without compromising long-term recurrence-free or overall survival, further supporting the clinical value of MRD-informed treatment decision-making.8 By more accurately distinguishing patients at high vs low risk of recurrence, MRD testing also has the potential to improve outcomes through earlier therapeutic intervention for patients with residual disease while reducing unnecessary treatment exposure, toxicity, and surveillance burden among patients with a lower likelihood of relapse.
Recent reviews and translational analyses further reinforce that ctDNA-based MRD assessment for colorectal cancer provides a highly sensitive and biologically relevant measure of residual disease burden that may identify recurrence months before conventional imaging or clinical detection.9,10 Emerging evidence also suggests that MRD testing may provide clinically meaningful information to support individualized discussions regarding adjuvant therapy intensity, duration, and longitudinal surveillance, particularly in situations where the risks and benefits of treatment are uncertain. In a recent comprehensive review, Ozluk et al highlighted studies demonstrating that postoperative ctDNA-positive patients may have recurrence risks exceeding 70%–80% in some cohorts, compared with substantially lower recurrence rates among ctDNA-negative patients, underscoring the strong prognostic discrimination provided by MRD assessment.10 Collectively, these findings support the clinical utility of MRD testing as a powerful prognostic and risk stratification tool in colorectal cancer care, with additional potential to inform more personalized and evidence-based management decisions.
ctDNA-Based MRD Testing in Bladder Cancer
Similarly, in bladder cancer, growing evidence supports the use of MRD testing to detect molecular evidence of residual disease following surgery and to help guide postoperative management decisions. Recent reviews and translational studies11,12 highlight the emerging clinical utility of ctDNA-based MRD assessment in muscle-invasive bladder cancer, demonstrating that postsurgical ctDNA positivity is strongly associated with recurrence risk and frequently precedes radiographic relapse by several months. Data from prospective studies and clinical trials such as IMvigor010 further suggest that MRD-positive patients derive the greatest benefit from adjuvant immune checkpoint inhibitor therapy, whereas MRD-negative patients may avoid unnecessary treatment and associated toxicity without compromising outcomes.13
Ongoing prospective studies, including IMvigor011 and TOMBOLA, continue to evaluate ctDNA-guided treatment strategies and may further establish MRD testing as an important tool for risk stratification, surveillance optimization, and treatment selection in bladder cancer care. Importantly, the FDA recently approved the first blood-based MRD diagnostic test in muscle-invasive bladder cancer,14 representing a major milestone in the broader transition toward personalized, MRD-guided cancer care, underscoring the growing recognition of the clinical value of MRD testing for recurrence monitoring, risk stratification, and more individualized posttreatment surveillance strategies.
Summary
Given the consistent clinical value demonstrated across studies, incorporation of MRD testing into appropriate clinical practice guidelines may help standardize evidence-based use of this important biomarker and further advance precision oncology approaches for patients with colorectal and bladder cancers.
Dr. Pritchard is Adjunct Associate Professor for George Washington University and Senior Advisor of Science Policy at the Personalized Medicine Coalition in Washington, DC.
DISCLOSURE: Dr. Pritchard is Senior Advisor of Science Policy at the Personalized Medicine Coalition (PMC) in Washington, DC. The PMC is an educational and advocacy organization representing innovators, scientists, patients, providers, and payers that promotes the understanding and adoption of personalized medicine concepts, services, and products to benefit patients and health systems.
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