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Circulating tumor DNA analysis shows promise for detection of colorectal cancer recurrence
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Circulating tumor DNA levels detected disease recurrence earlier than conventional postoperative surveillance among patients with resected colorectal cancer, according to results of a retrospective study published in JAMA Oncology.
The results add to evidence that circulating tumor DNA (ctDNA) is a sensitive marker of tumor burden and demonstrate the potential value of ctDNA analysis in stratifying these patients based on recurrence risk, according to researchers.
“Serial ctDNA is a very promising test, but how it could be best used in the clinic to improve patient outcomes remains the subject of ongoing clinical investigation,” Jeanne Tie, MD, FRACP, medical oncologist and associate professor at Walter and Eliza Hall Institute of Medical Research in Australia, told HemOnc Today. “There are several ongoing randomized clinic trials testing a ctDNA-guided management strategy compared with standard surveillance or management protocol. Until the results from these studies becomes available, I do not think this test should be routinely offered in the clinic.”
Previous studies have demonstrated that ctDNA levels can be an early indicator of disease recurrence in patients with stage II, locally invasive or metastatic colorectal cancer. The best surveillance protocol for patients with resected, nonmetastatic colorectal cancer, however, remains unclear.
Tie and colleagues analyzed 58 patients (median age, 69 years; range, 47-83; 59% men) with stage I to stage III colorectal cancer who underwent surgical resection to determine whether serial ctDNA levels detected disease recurrence earlier than conventional postoperative surveillance.
Researchers collected blood samples for ctDNA analysis 1 month after surgery and every 3 to 6 months afterward. In total, they collected 319 samples.
Eighteen patients received adjuvant chemotherapy at the recommendation of their physicians.
Researchers followed patients until they detected metachronous metastases or for a median of 49 months.
Results showed a disease recurrence rate of 77% (n = 10) among the 13 patients with positive ctDNA levels. Median time to recurrence following resection was 9 months (range, 5-52).
None (95% CI, 0-7.9) of the 45 patients with negative ctDNA experienced disease recurrence.
Researchers observed that ctDNA detection preceded clinical and radiologic indications of recurrence by 3 months.
Among the 48 patients who did not experience relapse, three (6%; 95% CI, 1.3-17) had positive ctDNA levels. Those positive levels became undetectable during follow-up.
The small sample size served as the study’s main limitation, and researchers noted that a larger prospective trial is needed to validate these results.
“Our findings provide further evidence of the potential value of ctDNA analysis in patients with early-stage cancer,” Tie and colleagues wrote. “[ctDNA] measurements can be easily obtained from blood samples collected during routine follow-up. Unlike radiographic imaging interpretations, ctDNA results are quantitative and reader-independent.”
Despite the small sample size, the results of this study, along with similar previous studies, begin to provide important insight into the ability of chemotherapy to clear any minimal residual disease that is tracked by changes to ctDNA levels over time, Van Morris, MD, assistant professor of department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues wrote in an accompanying editorial.
“Future trials in colorectal cancer 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,” Morris and colleagues wrote.
“Based on findings from [this study and others], ctDNA assays can be used to classify recurrence risk for patients with nonmetastatic [colorectal cancer] after standard-of-care treatment, and perhaps may be better than the commonly used clinical, laboratory and pathological risk factors in this setting,” they added. “Likewise, ctDNA assays may identify patients with early-stage [colorectal cancer] and no detectable residual tumor DNA who may be suitable for de-escalation approaches, given their associated favorable prognosis.” – by John DeRosier
For more information:
Jeanne Tie, MD, FRACP, can be reached at tie.j@wehi.edu.au.
Disclosures: Tie reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Morris reports travel expenses from Array Biopharma. Please see the editorial for all other editorial authors’ relevant financial disclosures.
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