ctDNA shows promise for clinical staging in patients with upper tract urothelial carcinoma


“This is the first study in upper tract urothelial carcinoma to show that ctDNA may be used to refine clinical staging and prognosis in these patients prior to surgery,” says Heather L. Huelster, MD.

In this video, Heather L. Huelster, MD, shares notable findings from the recent European Urology study “Novel Use of Circulating Tumor DNA to Identify Muscle-invasive and Non–organ-confined Upper Tract Urothelial Carcinoma.” Huelster is an assistant professor of urology at Indiana University School of Medicine in Indianapolis.


What were some of the notable findings? Were any of them surprising to you and your coauthors?

First off, detection of ctDNA in patients with treatment-naive high-grade upper tract urothelial [cancer] is feasible. All but 1 of our accrued patients appropriately processed plasma sample yielded sufficient ctDNA for evaluation. And the molecular alterations in the plasma were highly concordant with somatic mutations from the mass urothelial tumors. So that sort of reinforces the potential utility of noninvasive plasma-based assays to capture the molecular characteristics of in situ upper tract tumors. Most notably, though, in this study, we use next-generation sequencing of plasma samples collected 1 to 2 hours prior to radical nephroureterectomy and found that in treatment-naive high-grade upper tract tumors, the detection of at least 2 molecular alterations in plasma ctDNA was strongly predictive of at least pT2 and/or lymph node positive staging at the time of surgery, with a sensitivity of 71% and a specificity of 94%. And then we also found that at a median of nearly 15 months of follow-up, of the 11 patients that were ctDNA positive, 5 developed disease progression and 4 succumbed to urothelial cancer. In contrast, only 1 of the patients that was ctDNA negative but did have pT4 disease suffered disease progression and died. So ctDNA positivity was also strongly associated with both shorter progression-free and cancer-specific survival. So this is the first study in upper tract urothelial carcinoma to show that ctDNA may be used to refine clinical staging and prognosis in these patients prior to surgery.

This transcript was edited for clarity.

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