A retrospective, single-center cohort study, which evaluated surveillance strategies of circulating tumor DNA (ctDNA), imaging, and measurement of carcinoembryonic antigen (CEA) levels in patients with resected colorectal cancer, found that ctDNA assay (Signatera; Natera) provides no definitive advantage compared with standard imaging and CEA measurement in the surveillance of patients with resected colorectal cancer.1
A total of 48 patients with curatively resected colorectal cancer underwent surveillance by ctDNA, imaging, and measurement of CEA levels. Fifteen patients had disease recurrence during surveillance. Disease recurrence was detected in 8 patients with positive ctDNA; in 9 patients using imaging; in 3 patients using CEA levels; and in 11 patients when combining imaging and CEA levels.
In this retrospective cohort study, we aimed to compare the sensitivity of a Clinical Laboratory Improvement Amendments–certified ctDNA assay for minimal residual disease (Signatera) with standard radiographic imaging and measurement of CEA levels in identifying early disease recurrence in patients with curatively resected stage I to IV colorectal cancer. This retrospective study was approved by and conducted under the institutional review board of the City of Hope National Comprehensive Cancer Center, Duarte, California, which did not require informed consent for this retrospective outcome study. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
These patients with colorectal cancer underwent surveillance with the Signatera ctDNA assay between September 1, 2019, and November 30, 2021.Patients were stratified by cancer stage, separating those with resected stage II to III disease to one group and resected stage IV disease to another. Patients followed a standard surveillance strategy of ctDNA every 3 months for 2 years and then every 6 months for 3 years. CEA level measurements were performed at the same interval as the ctDNA assay. Imaging studies included yearly CT scans for 5 years for patients with low-risk stage II disease and every 6 months for 2 years and were also initiated every year for 3 years for patients with high-risk stage II and III disease. Imaging studies were performed every 3 months for 2 years and then every 6 months for 3 years for resected stage IV disease. Imaging studies were performed within the National Comprehensive Cancer Network guidelines. Researchers studied patient demographics, tumor location, pathological and clinical stage of disease, site of resected metastatic disease in stage IV disease, radiology reports, pathology reports, CEA results, ctDNA results, and subsequent surgical interventions.
When comparing sensitivity of ctDNA and imaging surveillance modalities, ctDNA had a sensitivity of 53.3% (95% CI, 27.4%-77.7%) and imaging had a sensitivity of 60.0% (95% CI, 32.9%-82.5%; P > .99). When comparing ctDNA and imaging plus CEA levels, the combination had a sensitivity of 73.3% (95% CI, 44.8%-91.1%; (P = .55). The sensitivity of CEA levels alone was 20.0% (95% CI, 5.3%-48.6%).
Investigators noted no significant difference in the time to identify disease occurrence with ctDNA having a median of 14.3 months, imaging a median of 15.0 months, and imaging plus measurement of CEA levels with a median of 15.0 months.
The median age range of patients was 60 (range, 34-85), and 58% of patients were male. Patients ranged between stage II and stage IV disease with 15 (31%) having stage II, 16 (33%) with stage III, and 17 (35%) with stage IV.
The findings suggest that ctDNA assay as a detection modality may not have significant advantages when compared to other methods such as imaging, CEA levels, or both combined. This study highlights the limitations of ctDNA in the surveillance of resected colorectal cancer. The results suggest the conducting additional studies before the universal adoption of ctDNA in clinical practice. Further, these findings confirm the ongoing relevance of CT imaging in the follow-up of patients with resected colorectal cancer. The reliability of ctDNA assay is put into question in conferring a sense of security regarding the risk of disease recurrence in colorectal cancer.
Fakih M, Sandhu J, Wang C, et al. Evaluation of comparative surveillance strategies of circulating tumor DNA, imaging, and carcinoembryonic antigen levels in patients with resected colorectal cancer. JAMA Netw Open. 2022;5(3):e221093. Published 2022 Mar 1. doi:10.1001/jamanetworkopen.2022.1093