The Holy Grail of colorectal cancer prevention – a reliable screening test that users don’t dread and avoid – appears to be getting close.
A novel test that detects telltale DNA markers in stool samples correctly identified 85 percent of colon cancers, 64 percent of significant precancerous polyps, and 90 percent of healthy samples, researchers announced Thursday in Philadelphia at a conference held by the American Association for Cancer Research.
“There is no other noninvasive screening test for colon cancer that comes close” to that accuracy rate, said David Ahlquist, a Mayo Clinic researcher who invented part of the technology and who is working with the commercial developer, Exact Sciences of Madison, Wis.
The DNA test is still experimental, hasn’t been validated under real-life conditions, and will take at least another year of development, he said.
This was a most interesting new test in development that was covered here at the AACR colorectal cancer biology to therapy meeting in the press briefing yesterday.
Current methods of colorectal cancer (CRC) screening for people over 50 involve either colonoscopy, which is invasive, or virtual colonoscopy, which is not covered extensively by insurers. Both require a not inconsiderate amount of time to do, not to mention the inevitable nervousness that goes with such procedures. Routine fecal tests currently available have unfortunately been shown to miss most advanced pre-cancers, so there is an real opportunity to develop a more sensitive and useful detection approach.
This new test takes a stool sample and looks for markers that indicate early presence of adenomas in the colon in a small validation study (n=59) by testing people who were being evaluated for CRC by colonoscopy, in other words, they had a high risk for CRC or were strongly suspected of having cancer. Such well characterised patients allows for quick segmentation into normal and cancerous groups, rather than waiting for long term epidemiology follow-up to see who develops cancer or not, which can take years.
According to the Mayo Clinic scientists, several combinations of methylation markers based on tissue DNA were found that discriminate colorectal neoplasia from normal mucosa. These were evaluated as part of the test validation process. The markers that were found to be useful included 3 methylated genes (TPFI2, BMP3, NDRG4), plus human DNA.
A huge advantage of this simpler approach is that I can see that potentially, primary care doctors could order it as part of routine screening at an annual physical, thereby finding colon adenomas early rather than waiting for a carcinoma to develop later in life.
The test from Exact Sciences looks at 4 genes known to be associated with the development of colorectal cancer and appears to be able to detect them with 85% sensitivity. Another DNA test is also being developed in Germany by Epigenomics AG, but differs in that it uses blood samples and looks at changes in Septin 9, which is not used in the Exact Sciences test. It is currently available to physicians in Germany.
The development of non-invasive easy to use tests like these is important because we all know that the earlier we detect abnormal growth, the easier it is to cure and improve overall outcomes for any cancer, as Bert Vogelstein emphasised in his talk the other evening and Tyler Jacks did in his keynote at the Xconomy meeting in Boston the other week. Colon cancer, for example, has a 90% cure rate when detected and treated early with surgery.
The lead investigator, Dr David Ahlquist, told me that the Mayo clinical studies with the Exact Sciences test are due to run until the end of 2012, so if all goes well we may see an approved validated test for wide scale testing available by 2013. Certainly the timeline is looking like the next couple of years rather than a much longer timeframe, which is very encouraging to all of us who have lost family members to the disease. While a better screening test won’t bring them back, it does offer hope that we may be able to avoid losing other people to the disease because their cancer was detected too late to do anything about it.
The pace and new advances in the early detection of cancer is something we can all be cheered about. Long may the trend continue!