Colorectal Cancer Screening:

EXACT Sciences offers an alternative for non-compliant patients resisting the current methods of colorectal cancer screening. The non-invasive test detects colorectal cancer in the average-risk population -- a problem that mostly affects adults older than age 50.

Colorectal cancer is the deadliest cancer among non-smokers in the United States, and the second most fatal after lung cancer. It is estimated that more than 130,000 Americans will be diagnosed with the cancer this year, and approximately 56,000 people will die from the disease, reports the American Cancer Society. Women exhibit a slightly higher incidence than men from this form of cancer.

If detected at an early stage, colorectal cancer has a cure rate of 95 percent, but this rate reduces significantly to less than 50 percent when detected later. Only 40 percent of individuals at risk are regularly screened for the cancer, with cost, inconvenience and discomfort often being cited as reasons for non-compliance.

Although cancer is associated with risk factors such as diet, environment and heredity, all cancers can be traced to genetic mutations in cells. "With the results of the human genome project, we certainly understand more about genomic progression of disease than we ever knew before," says Don Hardison, president and chief executive officer of EXACT Sciences in Maynard, Mass. "And the disease that we probably know as much about among the cancers as far as how it grows from a genomic base is colorectal cancer."

Hardison mentions further that with EXACT Sciences' PreGen-Plus screening test, "You're actually getting a direct measure of mutations in DNA. In reality, cancer is a disease of the DNA. So, this is getting down to the common denominator of cancer."

PreGen-Plus isolates the human DNA that is shed in the colon every day and carried out of the body in stool. Analysis of a stool specimen determines whether specific molecular changes associated with colorectal cancer and pre-cancerous lesions are present. The screening test requires no dietary modification or bowel preparation. Patients can collect a stool sample in the privacy of their homes and ship it in specially-designed packaging to LabCorp's facilities for analysis. Tests results are then sent to patients' physicians for use in connection with future monitoring and treatment.

"We felt that we could develop a technology that would be non-invasive and it would have the kind of sensitivity and specificity that would allow people to want to do the test and comply with it -- therefore ultimately pick up cancer earlier and save their lives," Hardison says. "It is a wonderful commercial opportunity, but it can help solve a huge public health issue."

Results from clinical studies of PreGen-Plus technology indicated a point sensitivity of 64 to 67 percent for invasive colorectal cancer, which is more than twice the accuracy of fecal occult blood testing and approximately 1.5 times more accurate than flexible sigmoidoscopy. In addition, the studies indicated a sensitivity of greater than 50 percent for advanced adenomas. Hardison adds there is also "a very high specificity. In other words, we don't have false positives. And again, the reason for that is because it's a direct measure of changes in the DNA, so you probably would not have false positives in that sense. Sixty-five to 70 percent is in the ballpark of what you would see from a pap smear, which has basically wiped out cervical cancer during the last 50 years. Or, the same ballpark as a mammogram and other screening tests that have shown the effect of reducing mortality for cancer. [PreGen-Plus] is good enough as a screening test at those level."

Hardison notes that whenever there is discussion about screening tests and performance characteristics of tests, the focus is often on the sensitivity and specificity of a test. However, "what we like to talk about is that the sensitivity of a test for a non-compliant patient is zero because they're not getting any test at all," he says. Adding further, Hardison says, "Compliance is the key. You have to have a test that people can comply with. Our belief is people will not comply with invasive tests and the non-invasive tests that are available out there aren't sensitive enough to pick up the cancer at the rate it could be picked up."

Recently, EXACT Sciences was approached by a physician whose patient was afraid of getting a colonoscopy. Although several of the patient's fecal occult blood tests were negative, the physician still wanted to pursue further tests. Based on the PreGen-Plus test, a polyp was detected and the patient underwent surgery for its removal. "The test works," Hardison stresses. "(The) higher likelihood that someone will comply with this test gives us great hope that we can really put a dent in this cancer that kills so many people."

Raising Awareness Among Medical Professionals

By Tina Brooks

Besides increasing public awareness about colorectal cancer, the National Colorectal Cancer Research Alliance (NCCRA) is educating the medical community. "One of the concerns that we have is if we reach someone, tell them to get tested and they decide to take action based on that, the physician that they go to needs to be aware of what is going on with colon cancer -- what the appropriate tests would be for colon cancer -- basically give that patient good information," says Steve Telliano, coordinator for NCCRA.

NCCRA is working with a number of specialty gastrointestinal groups and medical experts to help educate general practice physicians about the importance of colorectal cancer screening. Through these partnerships, the alliance is distributing interactive CD-ROM to medical professionals. The CD-ROM provides information about colorectal cancer screening options, treatments and the latest studies, as well as videos showing screening procedures.

Telliano adds that NCCRA will eventually offer educational materials geared for nurses. "Clearly, nurses are going to play an important role in all of this because nurses are an important part of the healthcare system when it comes to being an advocate for the patient, making sure the patient is informed, taking charge of their healthcare and helping the patient understand that the patient has a role to play in their own personal healthcare as well."