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Performance characteristics of a tumor-informed circulating tumor DNA (ctDNA) minimal residual disease (MRD) assay in stage 1-3 colorectal cancer (CRC) in clinical practice
Background
Detection of MRD has emerged as a tool for risk stratification in patients with early stage CRC with potential implication for adjuvant therapy. Recently, the sensitivity of MRD testing for early detection of tumor recurrence/ metastasis compared with conventional imaging has been questioned. We sought to evaluate the diagnostic performance characteristics of the Signatera™ ctDNA assay in patients with stage 1-3 CRC at West Cancer Center and Research Institute (WCCRI).
Methods
Patients with CRC who received ctDNA MRD testing 3-8 weeks after curative surgical resection for stage 1-3 disease from 12/2019 to 02/2022 were evaluated. Both patients with single testing and serial ctDNA assays were included. Individual chart review was performed to collect demographic information, verify diagnosis, stage, pathology, ctDNA and imaging results, and treatment course. ctDNA positivity rates were calculated and analyzed by diagnosis, stage, and clinical course.
Results
MRD results from 104 patients were available, 64 of which had sequential results. Positivity rate at initial testing was associated with stage: stage 1 0/9 pts, stage 2 5/40 (12.5%), stage 3 15/55 (27%). In the 64 patients with sequential data, conversion from negative to positive occurred in 7/50 (14%), 8/14 patients initially positive results converted to negative after adjuvant therapy, 5 of which developed ctDNA positivity in further monitoring after 3-14 months (range) with to date 4 recurrences confirmed by imaging. 27/104 patients were found to be ctDNA positive at any time point of which 2 patients were initially ctDNA negative with presence of overt disease (1 small pulmonary metastases, 1 incidentally found peritoneal nodule). In sequential ctDNA monitoring, both patients eventually showed positive ctDNA results. Only 1 patient had a false positive result at low Mean Tumor Molecule level (0.06 MTM/mL).
Conclusions
Tumor-informed ctDNA MRD testing has very high sensitivity and specificity, but a one-time negative test result does not preclude the presence of metastatic disease, in particular with regard to pulmonary and peritoneal tumor manifestations. Prospective randomized and non-randomized studies are underway to further assess the clinical utility of ctDNA MRD testing in early stage CRC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
