RSNA News - May 2005

CTC Trial Adds More Fuel to Ongoing Debate

We need to really understand if CTC is going to be a suitable technique for screening and how it compares with colonoscopy.

— C. Daniel Johnson, M.D.

CT colonography (CTC) has come a long way in the 10 years since radiologist David Vining, M.D., from Wake Forest University, unveiled his invention in Wagnerian style at a meeting of the Society of Gastrointestinal Radiologists. To the accompaniment of “Ride of the Valkyries” from “Die Walküre,” Dr. Vining used a computer mouse to navigate a “fly-through” of a volunteer’s colon.

The following years have brought a number of clinical trials, a consensus statement published this past March, and now, a 15-institution trial that will examine CTC’s value as a front-line screening tool in a head-to-head comparison with the current gold standard, colonoscopy. During the one-year trial, coordinated by the American College of Radiology Imaging Network (ACRIN), participants aged 50 or older will undergo CTC followed by a traditional colonoscopy on the same day.

“The primary aim of our study is to determine the performance of CTC for the detection of polyps one centimeter or larger,” said principal investigator C. Daniel Johnson, M.D., of the Mayo Clinic in Rochester, Minn. “All polyps five millimeters or larger will be reported and removed. We’re most concerned about polyps 10 millimeters or larger. Smaller polyps will be removed at the discretion of the gastroenterologist doing the endoscopy.”

Dr. Johnson said the secondary aims are to:

• Evaluate patient acceptance of CTC and willingness to have a repeat examination in comparison to optical colonoscopy
• Describe various morphologic features, distribution and frequency of flat colonic lesions
• Estimate the accuracy of CTC in detecting flat lesions in the colon
• Describe prevalence and clinical significance of extracolonic abnormalities detected in the course of a CTC examination
• Describe various methods of CTC evaluation
• Assess differences in software platforms
• Analyze the effect of electronic subtraction on the sensitivity to polyps and aspects of reading

In addition, the researchers will develop a well-annotated database of CTC case materials for future study, and will be able to assess the cost-effectiveness of CTC compared to other colorectal cancer screening tests.

“This trial is important because there are conflicting data on the performance of CTC,” explained Dr. Johnson. “There have been two multicenter trials showing CTC’s performance to be intermediate to mediocre, and one trial showing CTC’s performance to be as good or slightly better than colonoscopy in a screening population. We need to really understand if CTC is going to be a suitable technique for screening and how it compares with colonoscopy.”

Perry J. Pickhardt, M.D., the lead author of the study showing CTC’s performance to be as good or slightly better than colonoscopy, said the ACRIN trial will be expensive and redundant.

“I think the intentions of the ACRIN investigators are very noble, and that this trial would have been timely several years ago, but we have already validated CTC for screening. Our CTC methods are readily generalizable and could be implemented immediately to address this important public health issue,” said Dr. Pickhardt,from the University of Wisconsin Medical School. “What made our trial so successful was the use of primary 3D evaluation and stool and fluid tagging. I am concerned that the ACRIN trial may report the use of both 2D and 3D polyp detection, but will mainly utilize CTC systems that are not truly capable of primary 3D evaluation; disappointing results will then be blamed on both techniques.”

He added that using 2D in a screening study is like looking for needles in a haystack. To underscore his belief that CTC needs no further validation, he points out that his Madison-based CTC program already receives third-party reimbursement for screening, with four HMOs that have covered screening CTC since April 2004.

“We’ve performed over 1,000 screening CTCs over the past year and have improved our methods to the point where they are much better than when we published in the New England Journal of Medicine,” Dr. Pickhardt said. “I fear there may be too much riding on the ACRIN trial since we already have a proven method. By stepping backward and possibly using lesser methods, we could kill the whole movement.”

Dr. Johnson countered that there’s too much at stake not to undertake the ACRIN trial. “The medical community at large is not convinced that Dr. Pickhardt’s findings are reproducible,” he explained. “Our best outcome would be to show that we really didn’t need to do this trial; however, that’s not where we are today. If it were, CTC would be widely reimbursed and everybody would be doing it. Also, the National Institutes of Health would not have provided a $7 million grant if the trial wasn’t needed.”

Dr. Johnson credits Dr. Pickhardt’s research for making the ACRIN trial possible. He added that in the ACRIN trial, every exam will be read twice—in 2D and 3D. “Perry read in 3D and came up with fabulous results, but that doesn’t mean 2D can’t be just as good,” he said.

Consensus Statement on CTC

A “Consensus on Current Clinical Practice of Virtual Colonoscopy,” published in the March issue of the American Journal of Roentgenology (AJR), casts additional light on the debate. Matthew A. Barish, M.D., from Brigham and Women’s Hospital in Boston, and colleagues surveyed 31 CTC experts.

“This was big news because many believed that the technique was still evolving, but the fact that we could reach consensus was quite important,” said Dr. Barish. “Almost 90 percent of the experts surveyed said that CTC was a credible screening method. The most common response, from 51.6 percent, was that virtual colonoscopy is currently a credible alternative screening method and should be considered the test of choice when a patient is unable or unwilling to undergo conventional colonoscopy.”

Most respondents to the survey said they believed that the optimal method of interpreting CTC should be primary axial review, with 3D used for problem solving. Fewer than half (44 percent) said they believed that the minimum method was still primary 2D with 3D for problem solving.

Dr. Barish agreed with Dr. Pickhardt that the debate over the use of 2D and 3D is no longer a debate. “Most people now realize that you really need a combination of the two methods,” he said. “There’s no way you can read virtual colonoscopy effectively today without a full combination of both techniques. I hope that the ACRIN trial doesn’t stress one to the detriment of the other.”

Dr. Barish said the ACRIN trial will build constructively upon his consensus survey and previous clinical trials, and that quality results will be driven by a high level of training for those performing CTC. He also said he hopes that the ACRIN trial does not set such a high level of fecal and fluid tagging that it’s unlikely to be used as a routine for screening in the future. “One of the concerns would be that they end up with very good results as well, but it’s difficult to follow that standard when a lower standard of tagging could have been used with the same good results,” he concluded.