ctDNA and urine DNA testing may help select bladder-sparing treatment in muscle-invasive bladder cancer
Studies in muscle-invasive bladder cancer found ctDNA predicted metastatic risk after bladder-sparing treatment, while urine tumor DNA was more sensitive for residual bladder disease. Data from RETAIN-2 and a PNAS study support molecular testing to help select patients for bladder preservation.
Circulating tumor DNA, or ctDNA, can predict metastatic risk in patients who receive bladder-sparing treatment for muscle-invasive bladder cancer, while urine tumor DNA may help detect residual disease confined to the bladder. Updated clinical trial data and a study published in the Proceedings of the National Academy of Sciences reported promising findings that may help identify patients who can safely preserve their bladder without compromising cancer outcomes.
In updated data from the phase 2 RETAIN-2 clinical trial, more than 70 patients with muscle-invasive bladder cancer received combination chemotherapy plus an immunotherapy known as nivolumab. Patients showing complete response entered active surveillance instead of being treated with immediate surgery, and overall, 80% of these patients remained metastasis-free after two years. Researchers also reported that a response-adapted bladder-preservation approach involving neoadjuvant chemoimmunotherapy can be considered in select patients.
Blood samples were analyzed for ctDNA at multiple timepoints during the study. Patients who were ctDNA-positive after treatment were much more likely to eventually develop metastasis. The absence of ctDNA predicted favorable outcomes, regardless of whether the patient’s bladder was removed or not, and patients with undetectable ctDNA either before or after treatment demonstrated an exceptionally low risk of metastatic recurrence.
The study also showed that ctDNA is not a good predictor of local recurrence within the bladder. While the surveillance group overwhelmingly remained free of metastases, 22 patients subsequently developed a recurrence of cancer within their bladder. Of these, 19 did not show an increase in ctDNA.
In a separate analysis of plasma ctDNA and urine utDNA from patients enrolled in a clinical trial evaluating a bladder-sparing treatment strategy, investigators reported that among patients who achieved a complete clinical response following systemic therapy, three-year bladder-intact survival reached 69 percent. Patients with detectable circulating tumor DNA prior to systemic therapy faced a significantly higher likelihood of developing metastatic disease. In contrast, only 4.5 percent of patients with undetectable baseline ctDNA went on to develop metastases.
The analysis also found that plasma and urine DNA testing provide complementary insights. Urine tumor DNA proved more sensitive than blood-based ctDNA for detecting residual disease confined to the bladder. Detectable urine tumor DNA in patients who otherwise appeared to have no evidence of cancer was associated with shorter bladder-intact survival, suggesting that urine-based testing may help uncover hidden cancer not captured by conventional assessments.
Researchers said ctDNA could be used to help select patients likely to benefit from a bladder-sparing treatment approach, while additional tests or biomarkers are needed to detect local recurrence early in patients who undergo active surveillance. Researchers will continue following patients from the RETAIN-2 trial for five years to study long-term outcomes of bladder-sparing treatment and are designing the RETAIN-3 clinical trial, with plans to use ctDNA as a predictive biomarker in treatment decision-making.