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Patients with non-muscle invasive bladder cancer, even after years of clear surveillance cystoscopies, can develop widespread metastatic disease de novo. This rare but real phenomenon questions the adequacy of current imaging surveillance guidelines for patients considered to have low-risk disease, suggesting a potential role for ctDNA.
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The TRACK-ER study shows ctDNA positivity isn't just a future risk predictor. Nearly half (44%) of patients with a newly positive ctDNA test were found to have metastatic disease on imaging. This suggests ctDNA often detects existing, micrometastatic disease that standard scans miss, challenging the distinction between early-stage surveillance and managing overt metastatic cancer.
A dual-biomarker approach may revolutionize bladder cancer monitoring. Experts suggest urinary tumor DNA (utDNA) is superior for assessing the local tumor in the bladder wall, while circulating tumor DNA (ctDNA) monitors systemic disease. A negative result on both tests could provide the confidence needed to safely skip radical cystectomy.
Circulating tumor DNA is a powerful tool for detecting systemic minimal residual disease but is not sensitive enough for local, non-muscle invasive recurrences. This limitation means traditional surveillance like cystoscopy remains indispensable, as a negative ctDNA test can provide a false sense of security about local control.
Professor Powles highlights a critical limitation of ctDNA in bladder cancer management. While excellent for assessing systemic risk, ctDNA may remain negative during a local, non-muscle invasive relapse (e.g., T1 cancer). This necessitates continued local surveillance like cystoscopy, even in ctDNA-negative patients pursuing bladder-sparing approaches.
The future of bladder cancer surveillance may involve using two types of liquid biopsies in tandem. A patient who is utDNA-positive but ctDNA-negative likely has a local, primary bladder issue. Conversely, a utDNA-negative but ctDNA-positive result suggests the cancer has already spread systemically, providing crucial information for treatment planning.
A positive ctDNA test in a patient with non-muscle invasive bladder cancer (NMIBC) is a red flag that may indicate more advanced disease than initially suspected. However, it should not be misinterpreted as definitive evidence of metastatic disease. It warrants further workup, as resecting the primary tumor can clear the ctDNA.
Experts suggest urinary tumor DNA (utDNA) may better reflect local disease in the bladder, while circulating tumor DNA (ctDNA) indicates systemic disease. Using both tests in parallel could provide a more complete picture, with dual-negative results potentially becoming a key criterion for safely pursuing bladder-sparing approaches.
Across multiple recent trials, a consistent finding is that if a bladder cancer patient's circulating tumor DNA (ctDNA) does not clear after treatment, it is an extremely poor prognostic sign. This strong signal suggests that these patients should likely be switched to a different therapeutic approach immediately.
New phase 3 trial data shows that the quantitative level of circulating tumor DNA (ctDNA) is directly proportional to recurrence rates in bladder cancer. Patients with the highest ctDNA levels have the worst outcomes, suggesting a gradient of risk that could be used for more precise patient stratification.
The RETAIN bladder-sparing trial revealed a key limitation of circulating tumor DNA (ctDNA): it does not reliably detect non-muscle invasive bladder cancer. This means ctDNA surveillance is insufficient for monitoring local recurrence in bladder preservation protocols and cannot replace regular cystoscopies.