Dr. Powles on the Rationale to Evaluate ctDNA in High-Risk Muscle-Invasive Bladder Cancer

Thomas Powles, MBBS, MRCP, MD, director, Barts Cancer Institute, discusses the rationale to evaluate circulating tumor DNA (ctDNA) in high-risk muscle-invasive bladder cancer.

It is known that patients with high-risk muscle-invasive bladder cancer have about a 50% chance of dying as a result of relapse following radical cystectomy, says Powles. As such, developing strategies to identify which patients are likely to benefit from therapy, as well as who is likely to relapse following surgery is an important area of ongoing research.

Results of the phase 3 IMvigor010 trial failed to show an improvement in disease-free survival with atezolizumab (Tecentriq) compared with observation in patients with high-risk muscle-invasive bladder cancer who recently underwent radical cystectomy or nephroureterectomy with lymph node dissection, says Powles.

During the 2020 ESMO Immuno-Oncology Virtual Congress, findings from an analysis of the trial showed that patients with ctDNA-positive disease were significantly more likely to relapse compared with those with ctDNA-negative disease, indicating that ctDNA can be used as a prognostic biomarker.

Taken together, it was noted that intervening with atezolizumab did not benefit the intent-to-treat patient population. Additionally, ctDNA may represent a better biomarker than PD-L1 expression and tumor mutational burden, which did not aid in identifying which patients were likely to benefit from atezolizumab, concludes Powles.