A new blood test targeting tumor DNA in colorectal (bowel) cancer patients has detected early signs of recurrence of the disease at twice the rate of the standard test currently used.
The ‘two gene’ test found methylated BCAT1 and IKZF1 DNA in blood in almost 70% of patients with recurrence, while only 32.1% tested positive for carcinoembryonic antigens (CEA). CEA monitoring is often used in practice for CRC patients who have undergone surgery.
Flinders University’s Professor Graeme Young, one of the authors of a study involving 122 cancer survivors post-surgery, said the high recurrence of colorectal cancer, which kills 600,000 people world-wide every year, meant that such an improvement in early and effective detection of recurrence could save more lives.
He said the new test had the potential to, “fill an urgent and unmet clinical need”. The findings of the study are to be published in the journal Cancer Medicine, published by Wiley.
Professor Young and his colleague, Flinders University’s Dr Erin Symonds, will present their findings at the Australian Gastroenterological Week Conference, which takes place in Adelaide from today until Wednesday 12 October.
“Given that 40% or more of patients in remission from CRC following initial treatment will develop recurrence, improved surveillance methods that accurately detect recurrence are essential for improving outcomes for patients,” says Professor Young, who played a fundamental role in establishing the Flinders Centre for Innovation in Cancer (FCIC).
“Data from this study reinforce previous findings that circulating tumour-derived DNA can be reliably detected in CRC patients with recurrence. 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 CRC by detecting more unsuspected recurrences and triggering earlier imaging studies.
“Additional prospective studies of the methylated BCAT1/IKZF1 test compared with CEA are ongoing.”
When diagnosed early, before cancer has spread, the relative five-year survival rate for CRC is 90%, but only approximately four out of 10 CRC cases are detected early.
Among individuals undergoing surgical treatment for CRC, recurrence occurs in 30 to 40% of all cases, the majority of which present in the first two to three years following initial diagnosis and treatment.
This study compared the sensitivity and specificity of the two-gene blood test for tumour-derived methylated BCAT1 and IKZF1 with those of CEA in patients undergoing surveillance for recurrent CRC 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% were positive for methylated BCAT1/IKZF1 (i.e. marker was detectable) while only 32.1% were positive for CEA (>5 microg/L), representing a significant two-fold sensitivity improvement with the two-gene test.
Among the 94 patients without clinically detectable recurrence there was no significant difference in the percentage positive (the false-positive rate) for methylated BCAT1/IKZF1 test compared to CEA.
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 tumour progression 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,” says Professor Young.
“We believe the 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.”
Some of the world’s leading experts on colorectal cancer will meet at the Adelaide Convention Centre this week for Australia’s first multi-disciplinary symposium on colorectal cancer screening, a highlight of this year’s Australian Gastroenterological Week Conference.
The special symposium is part of Flinders University’s 50th Anniversary celebrations and will also look at the impact of diet and lifestyle, whether screening can eradicate the disease, and the role of GPs in tackling one of the major cancers of our time.
It follows a panel discussion facilitated by the broadcaster, Richard Aedy, who will draw upon the expertise of Flinders University’s Professor Graeme Young AM, and The University of Melbourne’s Associate Professor Alex Boussioutas and Professor Finlay Macrae AO, as they focus on how to eradicate colorectal cancer for good.
The Gastroenterological Society of Australia sets, promotes and continuously improves the standards of practice, training and research in gastroenterology and hepatology in Australia. http://www.gesa.org.au/about.asp?cid=4&id=5