The detection of fragments of circulating tumor DNA (ctDNA) in the bloodstream for diagnosing the presence or recurrence of cancer is growing in interest in healthcare research. The ctDNA shed from a tumor can now be detected reliably in the clinical laboratory by locating certain genes that are methylated in colorectal cancer (CRC) cells but typically not methylated in normal blood cells.

In 2016, the FDA approved the first ctDNA test for CRC screening based on methylation detection. EpiPro colon (Epigenomics AG) is characterized by a sensitivity of 48.2% and a specificity of 91.5% for cancer. Its performance compares with fecal immunochemical tests (FITs), which have a sensitivity of 65% or greater and a specificity of about 95%.

With approximately 50,000 deaths each year, CRC is among the leading causes of cancer-related mortality in the United States. Although highly treatable when detected early, only 25-50% of CRCs are caught when a cure is very likely. With at least one-third of CRCs recurring after initial treatment, vigilant surveillance is warranted. Current monitoring tools, however, are either prohibitively expensive for routine care or lack adequate sensitivity to reliably detect disease. The guideline-recommended blood test for recurrence monitoring—carcinogenic embryonic antigen (CEA)—has significant limitations, with many false negative and false positive tests. More accurate tests are needed to improve early detection of recurrence when effective treatment is still feasible. Surgical resection of metastatic CRC can achieve 5-year survival in 25% to 44% of patients, compared with just 8 months if untreated.

A new test developed for recurrence monitoring, Colvera (Clinical Genomics), that measures the presence of methylation in two well-characterized genes associated with CRC development (BCAT1 and IKZF1), became available in late 2016. In initial clinical studies, Colvera detected twice as many recurrent CRC cases as CEA and also compared well with FIT in a larger screening cohort. Although it is not yet clear if earlier detection results in reduced mortality, further studies are planned to determine if the new test can improve early detection of metastatic CRC and improve outcomes for these patients.

While continued evaluation is needed to determine the long-term value of ctDNA testing in real-world settings, it is an exciting time in CRC care. Encouraging evidence suggests that emerging tests for ctDNA will provide new options for screening and, importantly, improved options for detection of recurrence after initial treatment.