Analysis of tumor-informed ctDNA for prediction of nodal metastases at radical cystectomy in bladder cancer

A study at the Cleveland Clinic (Cleveland, OH)evaluated wheter pre-surgical tumor-informed circulating tumor DNA (ctDNA) predicts pathological nodal status at radical cystectomy for bladder cancer. The study prospectively analyzed 40 patients with non-muscle-invasive and muscle-invasive bladder cancer who underwent radical cystectomy with pelvic lymph node dissection (LND) and pre-surgical tumor-informed ctDNA testing. Of 40 patients, 27 (68%) were ctDNA-negative and 13 (32%) were ctDNA-positive. Pathologic nodal metastases were identfied in seven patients (18%). For nodal metastases, ctDNA demonstrated a sensitivity of 86% (95% CI 49-97), a specificity of 79% (62-89), and negative predictive value of 96% (82-99). In pooled descriptive analysis including 149 patients, the negative predictive value remained high ad 92% (95% CI 84-97). A (simulated) ctDNA-guided omission strategy could have avoided LND for 27 of 40 patients (68%0, with one false-negative case (3.7%) with subsequent recurrence. The authors conclude that pre-surgical tumor-informed ctDNA showed high negative predictive value for nodal metastases at radical cystectomy.