ASCO 2026 | ctDNA monitoring & outcomes in bladder cancer treated with EV & pembrolizumab

This was a retrospective study that we undertook among two institutions, so my institution at UCSF and also my collaborators at University of Oklahoma, where we looked at ctDNA monitoring for patients with metastatic urothelial cancer getting treatment with atezolizumab-based regimens. Most of those patients receive atezolizumab and pembrolizumab, though some receive atezolizumab monotherapy. Again, these are all patients with metastatic disease, and we track their ctDNA prior to and throughout the course of treatment. What we found is the highlights are basically that most patients with metastatic disease do have positive ctDNA, even at baseline. It was over 90% of patients, 93% to be exact. And for most of those patients, then we can track ctDNA during treatment, and that potentially informs how well patients do on treatment. We do see that ctDNA patterns or pattern of ctDNA change does correlate pretty well with outcomes that we see. Specifically, the patients that do the best are those whose ctDNA goes down, especially those whose ctDNA goes from positive to negative, almost all of those patients have responses to treatment that are then documented on scans. And generally speaking, those patients do pretty well. They have longer progression-free survival, overall survival, than patients whose ctDNA does not go down. Unfortunately, the patients who do the worst are those whose ctDNA goes up while they’re on treatment. Again, that is perhaps somewhat intuitive, but it’s another useful marker for us to know even earlier than we get scans of who’s benefiting and who isn’t benefiting. And this is all, I should stress, hypothesis-generating because this is a retrospective study. ctDNA was not measured at consistent intervals, not like it would be in a clinical trial. These were patients getting basically standard of care treatment within the form of therapy, and then we measured their ctDNA, you know, when we could. But, you know, we do see some important hints there that there are patient populations we can identify who are clearly benefiting from pembrolizumab, also those who may not be benefiting as well. And potentially those patients we can think about future clinical trials to intensify treatment even earlier than we see progression on scans. And certainly in some instances, it can even influence our clinical decision-making. We can maybe obtain scans earlier in patients whose, you know, CT DNA pattern looks concerning, where it’s, you know, not going all the way to negative or, of course, where it’s rising. So, again, I would say it’s early data. It was only about 100 patients, but I think potentially informative and something to follow up on in larger studies and certainly prospectively as well.

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