Clinical Edge

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ctDNA predicts recurrence in nonmetastatic colorectal cancer

Key clinical point: Circulating tumor DNA could be used to predict disease recurrence in patients with nonmetastatic colorectal cancer (CRC).

Major finding: The sensitivity of ctDNA testing for disease recurrence was 100%.

Study details: An observational study of 58 patients with nonmetastatic colorectal cancer.

Disclosures: The study was funded by the Virginia and D.K. Ludwig Fund for Cancer Research, the Commonwealth Foundation, the John Templeton Foundation, and others. The investigators reported financial relationships with PapGene, Sysmex, Eisai, and others.


Wang et al. JAMA Onc. 9 May 2019. doi: 10.1001/jamaoncol.2019.0512.


Based on recent findings of a study conducted by Wang et al. and an increasing amount of research, circulating tumor DNA (ctDNA) testing “will likely revolutionize” postoperative management for patients with early-stage colorectal cancer (CRC), according to Van Morris, MD; Arvind Dasari, MD; and Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“The ability to optimize adjuvant chemotherapy recommendations for patients with resected CRC has been historically limited by the use of clinicopathologic characteristics, which imperfectly prognosticate the risk for recurrence,” the doctors wrote in a JAMA Oncology editorial accompanying the article by Wang et al.

In the study by Dr. Wang and associates, “clinical recurrence was strongly linked with ctDNA detection at the time of recurrence,” the doctors wrote, adding that “the absence of ctDNA was highly associated with excellent oncologic outcomes.” These associations translated to predictive advantages, as “[ctDNA] status outperformed traditional risk factors, including the pathological stage, in stratifying patients’ risk for recurrence.”

“With the implications of ctDNA status for recurrence risk, the question remains regarding how this exciting technology can be used to improve the standard practices for CRC,” the authors of the editorial wrote, noting that the National Comprehensive Cancer Network currently recommends monitoring with imaging studies, carcinoembryonic antigen (CEA) tests, and endoscopies. “ctDNA positivity may eventually serve as a biomarker for high-risk patients for whom a more aggressive systemic treatment against residual micrometastatic disease may be advantageous,” they wrote.

They also highlighted how, in the Wang et al. study, chemotherapy was associated with conversion from ctDNA positivity to negativity in one patient, a phenomenon that has been observed in other trials. “Interpretation of these data is limited by a small sample size of patients,” the doctors wrote, “but these findings nonetheless begin to provide important insight into the ability of chemotherapy to clear minimal residual disease, as tracked by serial changes in ctDNA status over time, which is associated with favorable prognostic implications for patients with early-stage CRC. Future trials in CRC and other solid cancers should assess ctDNA clearance more robustly as a surrogate marker for disease-free survival in patients undergoing definitive therapies for their solid tumors.”

“At present, payers in the United States have not yet approved the routine use of ctDNA technologies in patients with early-stage CRC after resection,” the doctors wrote. “However, compelling data on ctDNA as a robust prognostic marker should be a reason to reassess coverage.”

“[With payer support and improved techniques], then this exciting ctDNA technology will likely revolutionize the routine postoperative management of early-stage CRC by providing a reliable, objective tool for oncologists,” they concluded.

Dr. Morris, Dr. Dasari, and Dr. Kopetz are affiliated with the University of Texas MD Anderson Cancer Center in Houston. Dr. Morris reported financial relationships with GuardantHealth and Array Biopharma. Dr. Kopetz reported relationships with Symphogen, Amgen, Merck, and Holy Stone.