The Potential of ctDNA as a Prognostic Biomarker in Patients With Colorectal Cancer

Circulating tumor DNA (ctDNA) may be able to be used to guide treatment decisions and risk stratify patients who have colorectal cancer (CRC), according to 2 studies published in the August issue of JAMA Oncology.

CRC is not only the third-most common cancer globally, but also many recurrence events are detected late, highlighting a “need for better biomarkers that can detect patients at high risk of recurrence,” explained the authors of one study.¹

They enrolled 130 patients with stage 1 to 3 CRC in Denmark and collected tumor tissue at surgery, as well as blood samples before surgery, 30 days after surgery, and then every third month until the patient died or withdrew from the study, or after 36 months. Before surgery, ctDNA was detectable in 88.5% of patients and after treatment, ctDNA analysis was able to identify 14 of 16 (87.5%) relapses.

The researchers discovered that patients who were ctDNA positive were 7 times more likely to relapse than patients who were ctDNA negative. Patients who were ctDNA positive were also 17 times more likely to relapse shortly after receiving adjuvant chemotherapy (ACT) and all of the patients who were ctDNA positive after ACT (n = 7) relapsed.

The second study included 58 patients with stage 1 to 3 CRC who underwent radical surgical resection in Sweden.² Blood samples were collected 1 month after the surgical procedure and every 3 to 6 months after. Only 18 patients received ACT.

A total of 319 blood samples were drawn from the study participants. The researchers found that 77% of patients who were ctDNA positive had disease recurrence. Meanwhile, none of the patients with negative ctDNA relapsed throughout follow-up, which was a median of 49 months. For the 3 patients who had positive ctDNA levels but did not relapse, their ctDNA levels fell to undetectable amounts during the follow-up period.

“Interpretation of these data is limited by a small sample size of patients, 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,” wrote Van Morris, MD; Arvind Dasari, MD, MS; and Scott Kopetz, MD, PhD, all of The University of Texas MD Anderson Cancer Center, in an editorial accompanying both studies.³

The authors noted that since both studies had small sample sizes, future research is needed to assess ctDNA clearance more robustly. They also added such findings should make US payers reassess coverage of routine use of ctDNA in patients with early-stage CRC after resection.

According to Morris, Dasari, and Kopetz, ctDNA technology could “revolutionize the routine postoperative management of early-stage CRC by providing a reliable, objective tool of oncologists.”

1. Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5(8):1124-1131. doi:10.1001/jamaoncol.2019.0528.

2. Wang Y, Li L, Cohen JD, et al. Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer. JAMA Oncol. 2019;5(8):1118—1123. doi:10.1001/jamaoncol.2019.0512.

3. Morris V, Dasari A, Kopetz S. Can circulating tumor DNA in early-stage colorectal cancer be more than a prognostic biomarker? JAMA Oncol. 2019;5(8):1101—1103. doi:10.1001/jamaoncol.2019.0503.

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