While promising, circulating tumor DNA (ctDNA) from plasma is not yet ready for guiding local treatment decisions in bladder cancer. Data from studies like RETAIN show it is insufficient for identifying patients with residual disease confined to the bladder, limiting its utility in bladder-sparing protocols.

Data from trials like Niagara suggests a powerful new paradigm for assessing treatment success. Combining urine tumor DNA (uTDNA) for local disease and circulating tumor DNA (ctDNA) for systemic relapse offers a more dynamic view than traditional pathology and is poised to become the superior surrogate endpoint in bladder cancer trials.

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.

Circulating tumor DNA (ctDNA) is a powerful biomarker for identifying high-risk bladder cancer patients. However, its imperfection presents a new clinical dilemma: with a ~12% relapse rate even in ctDNA-negative patients, clinicians must decide whether to withhold adjuvant therapy and accept that risk, or overtreat the 88% who are likely cured.

Upcoming trials like RETAIN and IMVigor011 are using circulating tumor DNA (ctDNA) to guide complex treatment choices in muscle-invasive bladder cancer. This biomarker-driven approach aims to personalize therapy, potentially enabling bladder preservation for some patients and identifying others who need additional adjuvant treatment.

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.

While circulating tumor DNA (ctDNA) is a powerful prognostic marker, it is not yet part of the formal "clinical complete response" definition for bladder-sparing trials. Experts lack data on its ability to predict the superficial, non-muscle invasive relapses common in this setting.

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.