From the Journals

ctDNA outmatches CEA for detection of colorectal cancer recurrence



For detection of recurrent colorectal cancer, circulating tumor DNA (ctDNA) may be more reliable than carcinoembryonic antigen (CEA), based on a recent Australian study.

Among 144 patients with a history of colorectal cancer, ctDNA testing offered a sensitivity of 66.0%, compared with 31.9% for CEA, reported lead author Erin L. Symonds, PhD, of Flinders University, Bedford Park, Australia, and colleagues, who noted that the two tests had comparable specificity.

According to the investigators, many patients with colorectal cancer who relapse are incurable because they have multiple unresectable metastases.

“This may be due to the poor sensitivity of the currently applied surveillance tools, with guidelines focused on radiological imaging (mostly yearly computed tomography [CT] scans) and regular blood tests for carcinoembryonic antigen (CEA),” the investigators wrote in Cancer. “There is a need to improve the timely detection of metastatic disease while it is still confined to a resectable state.”

To this end, the investigators compared ctDNA testing with CEA testing in a real-world setting. Initially, 548 patients were enrolled. The final dataset included 144 of these patients, all of whom were disease negative on CT or MRI after surgical resection or neoadjuvant therapy. Most exclusions were due to unavailability of imaging results. Circulating tumor DNA testing evaluated methylation levels of BCAT1 and IKZF1 (COLVERA test, Clinical Genomics Pty, North Ryde, New South Wales, Australia) . The LIAISON CEA test was used to measure CEA plasma concentration.

After a median follow-up of almost 4 years, 50 out of 144 patients had disease recurrence, most of which involved distant metastasis (74%). As described above, the sensitivity of ctDNA was higher than CEA by a wide and significant margin (66.0% vs. 31.9%; P less than .001). The superior sensitivity of ctDNA was observed regardless of whether recurrence was locoregional (76.9% vs. 15.4%; P = .006) or distant (62.1% vs. 38.2%; P = .044). Specificity was not statistically different between ctDNA (97.9%) and CEA (96.4%). Multivariate analysis showed that ctDNA was an independent predictor of recurrence, while CEA was not.

“In conclusion, the methylated BCAT1/IKZF1 ctDNA test is twice as sensitive as CEA for detecting recurrent CRC during the monitoring of patients after their initial treatment,” the investigators wrote.

The study was funded by the National Health and Medical Research Council, Clinical Genomics, Cancer Council SA’s Beat Cancer Project, and others. The investigators reported additional relationships with Eiken Chemical and the Commonwealth Scientific and Industrial Research Organisation.

*This story was updated on Jan. 10, 2020.

SOURCE: Symonds et al. Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695.

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