Can Aydogdu, MD on using ctDNA to predict nodal metastases at cystectomy

In this video, Can Aydogdu, MD, discusses findings suggesting that preoperative tumor-informed circulating tumor DNA (ctDNA) testing may help identify patients undergoing radical cystectomy who are at very low risk for lymph node metastases. Aydogdu is a urology resident at Ludwig-Maximilians-University München in Munich, Germany.

Aydogdu explained that although pelvic lymph node dissection (LND) remains the standard of care during radical cystectomy because of its staging and potential therapeutic benefits, the procedure also increases operative time and carries risks such as lymphocele formation, lymphedema, and vascular injury. He noted that clinicians currently lack a reliable biomarker to identify patients who are unlikely to benefit from LND. The study was therefore designed to assess whether preoperative tumor-informed ctDNA testing using the Signatera assay could predict pathologic nodal status in patients undergoing radical cystectomy.

The prospective study included 40 patients with non–muscle-invasive and muscle-invasive bladder cancer who underwent radical cystectomy with pelvic LND and preoperative tumor-informed ctDNA testing. Among all patients in the cohort, ctDNA demonstrated an negative predictive value (NPV) of 96% (95% CI, 82 to 99). The assay also demonstrated a sensitivity of 86% (95% CI, 49 to 97) and specificity of 79% (95% CI, 62 to 89) for detecting nodal disease.

To explore the potential clinical implications of these findings, the investigators modeled a hypothetical ctDNA-guided approach in which LND would be omitted in patients with negative ctDNA results. This simulated strategy could have avoided LND in 27 of 40 patients (68%), with only 1 false-negative case (3.7%) that later experienced recurrence. Aydogdu also emphasized the reproducibility of the findings, noting that a pooled descriptive analysis incorporating an independent cohort of 149 patients maintained a high NPV of 92% (95% CI, 84 to 97).

According to the authors, these results support prospective validation of tumor-informed ctDNA as a biomarker to identify patients at low risk for nodal metastases and to guide future trials evaluating biomarker-directed surgical management.

REFERENCE