Powles et al. Molecular residual disease detection in resected, muscle-invasive urothelial cancer with a tissue-based comprehensive genomic profiling–informed personalized monitoring assay. Frontiers in Oncology. Volume 13. July 13, 2023. https://doi.org/10.3389/fonc.2023.1221718.
Background:
Circulating tumor DNA (ctDNA) detection following surgery may be a useful biomarker to identify patients with urothelial cancer at high risk of relapse. Recent data suggests that early detection of postsurgical molecular residual disease (MRD) using ctDNA analysis may enable appropriate patient risk stratification and timely adjuvant treatment decision-making.
Study details:
Researchers evaluated Foundation Medicine’s widely available comprehensive genomic profiling (CGP) platform as a source of variants for tracking of ctDNA when analyzing residual samples from IMvigor010, a randomized adjuvant study comparing atezolizumab to observation after bladder cancer surgery.
Current methods often involve germline sampling and white blood cell sequencing, which is not always feasible or practical, to filter out germline and clonal hematopoiesis (CH) variants. In this study, researchers used FoundationOne®Tracker, a personalized ctDNA monitoring assay utilizing tissue baseline derived from the clinical trial assay version of FoundationOne CDx, across 2-16 variants to detect ctDNA following surgery.
Across 396 analyzed patients, the prevalence of potentially actionable alterations was comparable to the expected prevalence in advanced disease. In the observation arm, 36% of ctDNA-positive patients had shorter disease-free survival and overall survival than ctDNA-negative patients. ctDNA-positive patients had improved disease-free survival and overall survival with atezolizumab versus observation. At 28 months of median follow-up, clinical sensitivity and specificity for detection of recurrence after surgery were 58% and 93%, respectively.
Why this matters:
FoundationOne Tracker is a pragmatic and potentially clinically scalable method, which can detect low levels of residual ctDNA in patients with resected muscle-invasive bladder cancer without germline sampling.
View the full publication on Frontiers in Oncology.