Few tests have been so anticipated by patients as non-invasive gastrointestinal diagnostics and screening. And as the capsule endoscopy race morphs into a marathon with a growing cadre of competitors, the original front-runner of a device that allows visualization of the digestive tract without sedation, intubation or insufflation released study results today indicating that more work is needed before its capsule camera can detect colon cancer as well as a colonoscopy.

Given Imaging's (Yokneam, Israel) PillCam Colon was proven safe enough to visualize the colon in a new 328-patient study reported in today's issue of The New England Journal of Medicine (NEJM), but the capsule camera failed to provide the sensitivity of a colonoscopy. Study investigators reported that inadequate bowel cleansing is to blame, and added that a second-generation device already in the works – with technological advances – would likely be more efficient in its job of detecting polyps and diagnosing colorectal cancer.

"Our target is not to replace colonoscopy," Homi Shamir, president/CEO of Given Imaging told Medical Device Daily. "We aim to create more awareness and offer a non-invasive solution to patients unwilling or unable to do standard colonoscopy. Fifty percent of the population in America who need a colonoscopy refuse to do the test. In Europe it's 80%. Even if our technology is not as good as colonoscopy, if patients refuse to do colonoscopies [and opt for PillCam Colon], even if you have 60% sensitivity, still it's a benefit to save lives."

The sensitivity for detecting large polyps (? 6 mm) and advanced adenomas was 64% and 73%, respectively. Standard colonoscopy sensitivity averages 90%.

An editorial in the current issue of NEJM highlighted this concern for the fact that the technology did a poor job of finding even the largest polyps: "Surprisingly, the sensitivity of capsule endoscopy was similarly poor for the largest lesions – capsule endoscopy detected adenomas 10 mm or larger in only 64% of persons who had them, and it detected colorectal cancer in only 14 of 19 persons with cancer (sensitivity for cancer, 74%; 95% confidence interval, 52 to 88)," wrote Michael Bretthauer, MD, Gastrointestinal Endoscopy Unit, Oslo University Hospital Rikshospitalet (Oslo, Norway) and the Cancer Registry of Norway. "Since the size of colorectal lesions is a predictor of the development of cancer, the relatively low sensitivity of capsule endoscopy for the detection of large adenomas is cause for concern."

But Shamir wasn't daunted, emphasizing that some kind of test is better than none for the tens of thousands of people who avoid having colonoscopies. Additionally, Given Imaging is working on a second generation PillCam Colon with efforts to push sensitivity levels nearer to the 90% average found with colonoscopy.

"People are dying and there is technology available to save them," Shamir said. "I was very surprised about the editorial."

Douglas Rex, MD, professor of medicine, Indiana University of Medicine (Indianapolis) and director of endoscopy at Indiana University Hospital, told MDD that, "It certainly can't compete with colonoscopy in its current state. The real question is how much better it can get. The company has made a newer version that's better in terms of the frames speed [the number of pictures it takes over time] and angle of view, which is part of the reason for the lower sensitivity."

The other problem, Rex said, is that even if a patient undergoes the standard bowel cleansing preparation, many will have colored mucus that remains in the colon and clouds the pictures. More laxatives won't help. One of the goals, he said, should be to discover ways to suppress or dissolve that mucus to enable clearer pictures. Doctors can cleanse the intestinal tract as needed in standard colonoscopy for a clear picture.

The multi-center study enrolled 328 patients between January 2006 and July 2007 with known or suspected colon disease. The primary endpoint of the study was detection of colorectal polyps and cancer. As with colonoscopy, PillCam Colon's sensitivity was significantly higher in patients with adequate cleansing levels.

Investigators were looking for two common types of colorectal polyps. Adenomatous polyps typically advance to cancer. And the larger they are, the greater the chance for malignancy. Hyperplastic polyps, which are rarely more than 5 mm in size, typically don't become cancerous.

The tiny, capsule-sized cameras swallowed by patients – measuring 11 mm by 31 mm – are made by Given Imaging in different FDA-approved versions to view the small intestines (PillCam SB), the esophagus (PillCam ESO) and now the colon with PillCam Colon, which is not yet FDA approved.

Rex, who has worked for Given Imaging as a consultant but wasn't involved in the current study, pointed out that capsule endoscopy begs the question: Will any new test for colon cancer have an impact on adherence?

"Is it really true that people who wouldn't have a colonoscopy would be willing to do this test?" he asked. "Capsule tests tend to be initially attractive to patients. But then you get down to the details such as the aggressive preparation, and if you have a polyp you still need a regular colonoscopy.

"You can't replace colonoscopy because it's the only way to remove polyps. It's probably not right to think about something replacing colonoscopy even if the sensitivity were equal. The potential role for tests like this is for patients who are either not willing or unable to have a colonoscopy."

Although Given was the first to market with capsule endoscopy, Innurvation (Columbia, Maryland) is developing a capsule and several other companies are developing technologies that facilitate capsule endoscopy, including Pentax (Montvale, New Jersey), Fujinon (Wayne, New Jersey), Olympus, Royal Philips Electronics (Best, the Netherlands) and Siemens (Malvern, Pennsylvania).

"When I first came to Given and realized there was no competition, I was very pleased to see one enter and it didn't affect us," Shamir said. "Competitors validate the technology. It's also giving us a chance to do better. We are the only company in this space that provides three capsules. So competition will just make us better."

The company plans to pursue FDA approval when the new version of PillCam Colon is ready for clinical trials, probably later this year. Shamir said he is confident that PillCam Colon's usefulness has been demonstrated and that it will be further proven with upcoming studies.

Given Imaging received the CE mark for the first-generation version of PillCam Colon in 2006 which is now available commercially in Europe, Asia, Latin America, Canada and Australia.