Circulating Tumor DNA Predicts Disease Recurrence for Resected CRC

By Michael Vlessides, /alert Contributor
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The results of a new study suggest that analysis of circulating tumor DNA (ctDNA) levels may help determine the risk of disease recurrence among patients with resected non-metastatic colorectal cancer.

Although the researchers acknowledged that the results need to be validated in a larger, prospective trial, they nonetheless believe the findings suggest that ctDNA analysis may ultimately complement conventional surveillance strategies as a triage test to stratify such individuals.

Tumor cell. Source: Getty

“For oligometastatic recurrences, particularly within the liver or lung, prompt surgical resection offers curative potential,” they wrote in a recent issue of JAMA Oncology. “Therefore, early diagnosis of disease recurrence has been a high priority.”

Nevertheless, the international, multi-center research team behind the trial noted that the optimal surveillance protocol for patients with resected, nonmetastatic colorectal cancer remains unclear. With that in mind, they set out to evaluate whether serial ctDNA levels might detect disease recurrence earlier than conventional postoperative surveillance. 

The study included 58 patients (median age 69 years; 34 males) with stage I, II, or III colorectal cancer who underwent radical surgical resection at four Swedish hospitals between February 2, 2007 and May 8, 2013. Of these, 18 received adjuvant chemotherapy at the clinician’s discretion; these physicians were blinded to ctDNA results. 

Blood samples for ctDNA analysis were collected at one month after the surgical procedure, as well as every three to six months thereafter. Each participant was followed up until metachronous metastases were detected, or for a median of 49 months.

The investigators compared the sensitivity and timing of ctDNA positivity with such conventional surveillance modalities as computed tomography scans and serum carcinoembryonic antigen tests in the detection of disease recurrence.

Data analysis was performed from March 1, 2009 to June 23, 2018. In total, 319 blood samples were collected from 58 participants. 

It was found that 45 of 48 patients with negative circulating tumor DNA levels were recurrence-free, while 10 of their 13 counterparts with positive circulating tumor DNA levels relapsed during follow-up (0%; 95% CI: 0%-7.9%). Interestingly, circulating tumor DNA positivity preceded radiologic or clinical evidence of recurrence in all 10 patients, by a median of four months.

As the researchers discussed, the findings help demonstrate the potential utility of ctDNA in stratifying patients with resected colorectal cancer. “Serial ctDNA levels during follow-up can precede disease recurrence prior to routine radiographic imaging,” they wrote. “In addition, ctDNA measurements had higher sensitivity in detecting recurrence compared with serum carcinoembryonic antigen levels (100% vs 60%).”

The researchers called for larger, prospective studies to determine whether the lead time provided by ctDNA measurements might be associated with improved clinical outcomes among these patients, as well as to validate the findings of the present trial. 

Nevertheless, they were encouraged by the study’s preliminary results, and the potential ease with which the method can be incorporated into clinical practice. “Circulating tumor DNA measurements can be easily obtained from blood samples collected during routine follow-up,” they added.

“Unlike radiographic imaging interpretations, ctDNA results are quantitative and reader-independent. Thus, ctDNA test could, in principle, be easily incorporated into routine follow-up to complement conventional modalities, such as CEA test and radiographic imaging, to help stratify patients’ risk for disease recurrence.”


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