ctDNA dynamics and recurrence patterns after organ-sparing trimodality therapy for bladder cancer

Trimodality therapy (TMT) is a bladder-sparing treatment approach for patients with muscle-invasive bladder cancer (MIBC). The association of circulating tumor DNA (ctDNA) with clinical outcomes in MIBC patients treated with TMT is poorly characterized. A study at two centers in Boston, MA, enrolled patients who underwent ctDNA evaluation at baseline and at regular intervals following TMT. Eighty-four patients had at least one ctDNA result. Fifty-nine patients had a ctDNA test performed prior to chemoradiotherapy (CRT), with detectable ctDNA in 19 patients (32%). Forty-six patients had paired pre- and post-CRT ctDNA available. Nearly all (29/31; 94%) patients with undetectable ctDNA prior to CRT also had undetetable ctDNA at the first post-CRT assessment, whereas 11 of 15 (73%) patients with detectable ctDNA prior to CRT converted to undetectable ctDNA followin CRT. Sixteen patients (19%) developed metastatic disease, and detectable ctDNA following CRT was strongly correlated with metastatic recurrence (p<0.0001). Conversely, no patients with an isolated muscle-invasive (n=5) or non-muscle-invasive (n=7) bladder recurrence had a post-TMT test demonstrating detectable ctDNA prior to recurrence. The authors conclude that ctDNA detectability is correlated with metastatic but not local disease recurrence in MIBC patients following TMT.