Positive trial results boost VC's prospects for broader screening role

Oct 15, 2007

BOSTON - There was more to celebrate than mere blue skies and the sun-drenched warmth of Indian summer when the International Symposium on Virtual Colonoscopy opened on Monday. Indeed, to those in attendance the outlook for virtual colonoscopy (VC or CT colonography [CTC]) may have seemed as bright. In the run up to this year's meeting, two major studies released in as many weeks had judged the virtual exam equivalent to optical colonoscopy in important measures of efficacy.

First, in late September, preliminary results of the ACRIN 6664 trial of 2,531 screening subjects in 15 U.S. centers demonstrated sensitivity of 90% for adenomatous lesions 1 cm or larger at VC. Then, a week later, Dr. David Kim and colleagues from the University of Wisconsin followed up with a New England Journal of Medicine report showing quite similar advanced adenoma detection rates for VC compared to optical colonoscopy in more than 6,000 subjects.

The upbeat news continued at the symposium, with word that virtual colonoscopy in two large European multicenter trials, IMPACT from Italy and the Munich Colorectal Cancer Prevention Trial, would demonstrate sensitivity of 91% and 100%, respectively, for detecting clinically significant lesions, with details scheduled for release on Tuesday.

What virtual colonoscopy advocates were really hoping for and didn't quite get, however, was news that the long-awaited consensus colorectal cancer screening guidelines under development would finally permit the inclusion of virtual colonoscopy as a colorectal cancer screening option, a process that would, presumably, open doors to broader acceptance of the exam, Medicare and private payor reimbursement, and down the road, maybe even better screening compliance among Americans age 50 and older.

Radiologists want to know "how and when CT colonography will be added to the guidelines for colorectal cancer screening," said program chair Dr. Joseph Ferrucci, a professor of radiology at Boston University School of Medicine. "We all understand that there are a lot of different complex issues: the natural history of colorectal polyps, cost efficacy, the interaction of radiologists and gastroenterologists, the public message to patients. These issues are not objective and straightforward; they are subjective and require a lot of give and take, and in this regard, it's been important that the relevant groups have been at the table to get things right."

The relevant groups at the table have had their work cut out for them. Under the auspices of the National Colorectal Cancer Roundtable Quality Assurance Committee, the American Cancer Society (ACS), the U.S. Multisociety Task Force, and the American College of Radiology (ACR) have labored to reach consensus on joint colorectal screening guidelines that respect the evidence in the literature and satisfy the divergent needs and approaches to screening of the major stakeholders, including gastroenterologists. The mammoth task is nearing completion, representatives said, but the results were not finalized and could therefore not be announced.

Technology has placed new demands on the guidelines process, they said. Patients and technology developers are now active participants along with researchers. Studies are performed quite differently, with different aims and results and measurement standards. And for one organization in particular, new guidelines are due.

The American Cancer Society's five-year colon screening guidelines, which currently include optical colonoscopy, flexible sigmoidoscopy, double contrast barium enema, and fecal occult blood testing as approved colorectal screening exams, are set to be replaced by the end of 2007, or thereabouts. Since 2003, two additional exams under consideration, virtual colonoscopy and stool DNA testing, have been called promising, but were said to lack sufficient evidence to recommend their inclusion in the screening protocol. For the screening of average-risk individuals, the American College of Gastroenterology has expressed a preference for conventional colonoscopy.

Dr. Bernard Levin, vice president of cancer prevention and population sciences at the University of Texas M. D. Anderson Cancer Center in Houston, gave an overview and history of colorectal cancer screening guidelines.

Robert Smith, Ph.D., director of cancer screening for the Atlanta-based American Cancer Society, joined in the discussion of the review process that he said would soon result in the joint publication of new ACS guidelines, which are currently in review. While avoiding specific disclosures of the draft conclusions being circulated, Smith's comments were positive with regard to screening virtual colonoscopy -- and were interpreted by prognosticators in attendance as a clear sign that VC would soon be included in the colon cancer screening armamentarium.

What has amounted to researching the research to develop new screening guidelines has been a daunting task, necessitating the development of priorities in assessing various tests, Smith said.

"The current evidence for the various tests -- and there's growing numbers of them -- have a number of limitations: for one thing prospective studies are uncommon, sample sizes tend to be small, and study participants often include higher-risk symptomatic patients mixed with screening patients," he said. "As the evidence for a value of a screening test matures, there tend to be less funds for large prospective studies than there might otherwise be. We've placed priority on prospective studies of asymptomatic adults, because we do recognize there are differences in the outcomes between average-risk and high-risk populations, especially when you've looked at studies that have colonoscopy including the series as a validation measure."

The evidence also shows that the cost and performance sensitivity of the various tests are widely variable, though some of the tests that are more expensive up-front can actually be more cost-effective over time, Smith said. Thus, an ostensibly lower-cost screening option such as flexible sigmoidoscopy, combined with fecal occult blood testing, has actually been shown to be more expensive than colonoscopy over 10 years, he said.

In addition, the inconsistency of test results, combined with a tendency for low screening compliance, led to a decision by the committee to favor tests that offer high sensitivity in a single exam rather than measurable results only with repeat testing over time -- so called programmatic effectiveness.

"It was the strong opinion of the guidelines committee that colon cancer prevention should be the primary goal of colorectal cancer screening," Smith said. "In the evaluation of existing literature, emphasis was placed on evidence of single-test sensitivity rather than program sensitivity.... We can say all day long that emphasis should be placed on program sensitivity because it can achieve measurably better results over time. But the data show very clearly that most Americans do not get regular screening tests. With respect to annual stool blood testing, series have shown that the proportion of adults who get repeat testing is really very low."

Another approved screening exam, flexible sigmoidoscopy, has been shown to have much lower sensitivity in low-volume office settings than in high-volume centers, leading the organization to discourage its use in low-volume practice settings, Smith said, which has also led to recommendations that patients be advised of the limitations of the exam.

The sensitivity of whole-colon structured exams, including virtual and conventional colonoscopy, can also vary considerably, and test sensitivity seems to drop most significantly in low-volume and low-experience settings, he said. One option has been to endorse accreditation programs for both exams, he noted.

"Accreditation programs should emphasize adherence to quality standards, including interaction with patients before and after the examination, procedure standards and monitoring, qualifications for examiners, feedback and medical audits, and ultimately standards for continuing medical education," Smith said.

"Let me just say that most of the guidelines committee has been hugely impressed, especially in recent days, with the progress by which the CT colonography community has accumulated data," Smith concluded, adding that performance variability and other issues associated with CTC have been abundantly addressed. "And of course we think the results of the ACRIN trial are really quite impressive," he said.

The draft guidelines document is currently being circulated for review by all parties, conference calls are being set up to facilitate communication, and once final consensus has been achieved, their joint publication is being arranged, Smith said.

"Every year we have seen continued evolution of CT colonography, and I think we are finally at the point where there's a lot of positive momentum in trying to get CTC out in the community," said Dr. Judy Yee, an associate professor and vice chair of radiology at the University of California, San Francisco, and chief of radiology at the San Francisco Veterans Affairs Medical Center. On the strength of the recent ACRIN 6664 results, the Veterans Health Administration is gearing up to implement virtual colonoscopy in its hospitals throughout the U.S., she added.

By Eric Barnes
AuntMinnie.com staff writer
October 16, 2007

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Study: primary 3D VC equivalent to colonoscopy, September 12, 2007

Gastroenterologists plan to perform VC, January 25, 2007

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