GU Cancers 2026 | NIAGARA: analysis of urinary and circulating tumor DNA in MIBC

So the NIAGARA trial was a large randomized phase 3 trial in muscle-invasive bladder cancer that investigated perioperative Durvalumab in addition to standard cisplatin, gemcitabine, neoadjuvant chemotherapy and it showed that the combination had a significant improvement in event-free survival and overall survival and also path-CR. So in a previous analysis of circulating tumor DNA in the Niagara trial, we found that ctDNA is prognostic at various time points in the course of treatment, so at baseline, after neoadjuvant treatment, and after surgery. We also found that the presence of ctDNA , so in the plasma, was very predictive for not having a pathological CR. However, the reverse was not true. So patients who were negative for ctDNA didn’t necessarily have a pathological complete response. So in this study that we are presenting here at ESMO, we are looking at the urinary tumor DNA to see if we can get more information in that way, especially on the primary tumor. So what we found is that urinary tumor DNA is present in most of the patients, so more often than circulating tumor DNA. And clearance of urinary tumor DNA by neoadjuvant therapy is a prognostic factor, so it’s favorable if you clear your urinary tumor DNA just like ctDNA We also found that Durvalumab has a higher chance of clearing urinary tumor DNA than in the standard arm, so with only chemotherapy. And if we look at pathological complete response, we found that urinary tumor DNA, the absence of urinary tumor DNA is more predictive for having a path CR. So about 72% of patients had a path CR if they had no urinary tumor DNA present anymore before surgery, which is different from circulating tumor DNA. So if we look at more detail in the pathological response in various categories of ctDNA and urinary tumor DNA, then we found that ctDNA is more indicative of invasive disease or systemic disease, so nodal metastases or distant metastases, whereas urinary tumor DNA is more indicative of the primary tumor, so residual muscle-invasive disease or non-muscle-invasive disease. And finally, we also found that urinary tumor DNA on top of circulating tumor DNA could have an additional layer of prognostic information. So in patients, especially who are ctDNA negative, the patients who are still urinary tumor DNA positive did worse than the patients who are double negative.

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