In a new report published by Young et al in Cancer Medicine,1 a two-gene circulating tumor DNA (ctDNA) blood test for postsurgical monitoring of colorectal cancer recurrence has been shown to detect twice the number of recurrence cases as carcinoembryonic antigen (CEA) testing, a standard-of-care component for colorectal cancer recurrence monitoring in patients who have undergone surgery. The test measures the presence of BCAT1 and IKZF1 gene methylation, a chemical modification associated with tumor growth and invasion. Preliminary data from this study were presented in January at the ASCO 2016 Gastrointestinal Cancers Symposium.2
Graeme P. Young, MBBS, MD, FRACP
“Given that at least 30% of patients in remission from colorectal cancer following initial treatment will develop recurrence, improved surveillance methods that accurately detect recurrence are essential for improving outcomes for patients,” said contributing study author Graeme P. Young, MBBS, MD, FRACP, Matthew Flinders Distinguished Professor, Flinders University Centre for Innovation in Cancer, in Adelaide, Australia. “Data from this study reinforce previous findings that ctDNA can be reliably detected in colorectal cancer patients. Furthermore, the results suggest that when used in ongoing surveillance of cases in remission, a positive BCAT1/IKZF1 test has the potential to establish a new approach for earlier detection of recurrent colorectal cancer by detecting more unsuspected recurrences and triggering earlier imaging studies. Additional prospective studies of the methylated BCAT1/IKZF1 test compared with CEA are ongoing.”
Among individuals undergoing surgical treatment for colorectal cancer, recurrence occurs in 30% to 40% of all cases, the majority of which present in the first 2 to 3 years following initial diagnosis and treatment.
Study Findings
This study compared the sensitivity and specificity of the two-gene blood test for methylated BCAT1 and IKZF1 with those of CEA in patients undergoing surveillance for recurrent colorectal cancer following induction of remission. Recurrence was assessed by clinical findings, blood testing, and periodic computed tomographic surveillance scans. A total of 357 volunteers were recruited. Recurrence status could be established for 220 subjects, of which 122 had blood samples available for analysis.
Of the 122 participants evaluated, 28 had recurrence and 94 had no clinically detectable disease. Among those with recurrent disease, 67.9% (19 of 28) were positive for methylated BCAT1/IKZF1 (ie, marker was detectable) whereas only 32.1% (9 of 28) were positive for CEA (> 5 ng/mL), representing a significant twofold detection improvement with the two-gene test. Among the 94 patients without clinically detectable recurrence, there was no significant difference in the percentage positive for methylated BCAT1/IKZF1 compared to CEA.
In this study population, sensitivity estimates of the methylated BCAT1/IKZF1 test were 75% and 66.7% for local and distant recurrence, respectively, compared with 50% and 29.2% for CEA. Nine patients were positive for both tests, while the two-gene test detected an additional 10 cases that CEA failed to detect in the blood sample collected closest to the time of radiologic assessment for recurrence.
“An inability to detect early molecular changes consistent with underlying tumorigenesis can result in recurrent colorectal cancer going undetected or being discovered in the later stages of disease when clinical intervention is less likely to be effective,” said Lawrence LaPointe, PhD, President and CEO of Clinical Genomics. “These data demonstrate that a blood-based ctDNA test for methylated BCAT1/IKZF1 routinely detects recurrence that CEA testing misses. We believe our two-gene test has the potential to fill an urgent and unmet clinical need, and are committed to advancing its clinical development as a new tool for improving patient outcomes.” ■
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