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Researchers at Northern Sydney Local Health District are attempting to devise a reliable molecular test to predict bowel cancer risk and potentially reduce the frequency with which patients require follow-up colonoscopies.
With the support of a Sydney Health Partners grant, NSLHD Director of Cancer and Palliative Care, Professor Alexander Engel and fellow principal investigator, University of Sydney’s Professor Mark Molloy, are using a pioneering process to take biopsies of polyps just before they are removed from patients when undergoing otherwise routine colonoscopies.
The molecular profiles of the biopsies are then identified in order to define “signatures” of genetic mutational load and microbiome profiles. Comparing the molecular testing with the results of standard pathology will enable the researchers to determine which molecular features indicate greater risk of developing cancer.
Professor Engel says that 80-90 per cent of bowel polyps will not develop into cancers.
“Colonoscopy is a great clinical tool,” he said, “but it’s not very pleasant for the patient and there’s a small chance of accidental bowel perforation, which can cause nasty complications. And colonoscopies place an enormous logistical and financial burden on the health system.
“If we had a technique to identify the patients at lower risk of developing bowel cancer, it would lead to an associated reduction in the need for follow-up colonoscopies.”
Between 2006 and 2016, the number of colonoscopies performed in Australia almost doubled and following the introduction of the National Bowel Cancer Screening Program in 2014, now exceeds one million procedures a year.
The purpose of these colonoscopies is to find and remove polyps from the large bowel. Although the polyps are normally benign, they have the potential to become malignant and their removal is a highly effective strategy for the prevention of bowel cancer.
However, Professor Engel says the current system for planning follow-up colonoscopies is far from perfect, and the huge number of colonoscopies for bowel polyps is driven not just by its effectiveness but also by doctors erring on the safe side.
“Currently, doctors look at the number, size and tissue-specific character of the polyps they’ve removed. The patient’s family history of cancer is also considered and following surveillance guidelines, we arrange for follow up in ‘one, three or five years,’” he said.
“We think that’s a crude assessment. The guidelines have simply not kept up with the advancement in molecular profiling techniques and don’t take into account what is happening at a genetic level in those problem polyps.”
Professor Molloy says the research aims to define how well the current risk assessment done in pathology matches the molecular profile.
“You could imagine cases where a polyp is just large enough in size to fall into a moderate or high risk category, but when you look at the molecular signature it actually correlates with low risk polyps. In those patients it might be suitable to delay follow up colonoscopy,” he said.
“We might also see the other extreme where we should be offering greater surveillance for an individual because their signature is of high-risk. We will model the differences in surveillance interval times between the two risk tools to assess the scale of difference and likely saving of hospital resources.”
Professor Engel says the project is a rare example of basic research and clinical service delivery being integrated to benefit patients.
“Projects like these are of huge importance because they shed new light on a very common problem and offer a solution that not only works but can be used on a large scale,” he said.
“I am very enthusiastic about the numbers and the implications of this project. We’ve already shown that collecting the biopsies is not the hard part – it makes hardly any difference to the efficient delivery of colonoscopies.”
Thanks in part to the preliminary work performed under the Sydney Health Partners grant, Professors Engel and Molloy have subsequently received a grant from the Cancer Council of NSW to expand their work over the next three years.
The Sydney Health Partners project is funded by using money provided by the Medical Research Future Fund through its Rapid Applied Research Translation scheme.