Interval Colon Cancers: Is Biology to Blame or Are We?

David A. Johnson, MD, Posted: 02/13/2012

Hello. I'm Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. A bevy of recent information might be of interest to you, and I would like to present some highlights of some very important, landmark studies that should influence our day-to-day colonoscopy practice.

Interval Cancer: Who Is to Blame?

Should interval colon cancer be blamed on biology, or are we partly to blame? The latter is the recognition that we are missing lesions. Serrated polyps are the lesions that are most likely being missed.

Until recently, the serrated pathway was not well recognized. We thought that all cancers evolved primarily through the adenoma carcinoma sequence -- the traditional Vogelstein model of an adenoma of any consequence progressing to cancer. Now we know that 10%-20% of cancers actually evolve through this serrated pathway, which is a different process. The serrated lesion, therefore, becomes an important progenitor for serrated cancers.

Serrated pathway cancers account for 10%-20% of all cancers and more than one third of interval cancers, and these patients have had colonoscopies. Therefore, the concern has been raised, at least in several studies of colonoscopy patients, that we lack protective features, and we may be missing these serrated polyps, particularly those in the proximal colon.

When we talk about proximal serrated polyps, the landmark that we use is beyond the sigmoid flexure -- behind the sigmoid colon. We are not necessarily referring only to right-sided polyps, but that is where these lesions are most likely being missed.

What are these lesions? There are 3 traditional types of histology:

The hyperplastic serrated polyp; The traditional serrated adenoma; and The dysplastic serrated polyp. These lesions are more common in the right colon.

The underlying prevalence of these lesions is just starting to be defined. However, if you look at prevalence studies and the development of polyps in patients who are undergoing screening colonoscopies, the incidence is probably not changing. The prevalence is increasing because we are recognizing them more.

Increasing Rates of Serrated Polyp Detection

A very nice study from a group at Boston Medical Center[1] looked at polyp detection in 2006 compared with the era of greater awareness (2007-2008). They found a 5-fold increase in the detection of serrated polyps. Therefore, the incidence is not increasing, but the prevalence increased with greater attention and recognition of what these polyps are.

Two very recent studies described the endoscopic features to aid in polyp detection for these serrated lesions. One article was published in Endoscopy in December 2011,[2] and the other was a very recent article in Gastrointestinal Endoscopy.[3]

These lesions tend to be found in the right colon. They are invariably flat, but uncommonly can be raised. A mucous cap will frequently be adherent to these lesions, and they tend to be mucus-secreting. Beneath the little mucous cap, fecal material can be detected. So, look for these lesions and wash off those areas. Sometimes these lesions will have a peripheral rim of debris or bubbles.

An obscuring of the vasculature is a very helpful feature. When you are looking at the blood vessels -- and not just looking for polyps -- look at the blood vessel patterns in the mucosa. This is very helpful. If you are unfamiliar with this technique, narrow-band imaging may be helpful in highlighting some of the disruption of the vasculature.

A disruption of the normal mucosal folds is another indicator of a serrated polyp. Look very carefully at this area, and think about a serrated polyp. Finally, a raised dome of accumulated material also could be a marker. These things are all very important in the discovery of serrated polyps.

Still Missing Serrated Lesions

The incidence of serrated polyps is a function of detection, and detection is still variable. If you look through some of the literature, the rate of missed serrated lesions ranges from 30%-50% in back-to-back tandem colonoscopy studies. This may reflect an earlier lack of understanding of the importance of serrated polyps.

More recently, a group from Indiana[4] looked at the detection of serrated lesions in 2 academic centers. This study included academic gastroenterologists who were expert colonoscopists. The rate of detection of serrated lesions ranged from 1%-18%, suggesting that this might be a real problem even among experts.

The key here is that being a serrated adenoma detector correlated with adenoma detection. If you are a good adenoma detector, you should be seeing serrated polyps emerging in your pathology reports. If you are not, then you need to start looking at these. Talk to your pathologist about whether they are accurate in their descriptions of what you might call, or what they might otherwise call, a "hyperplastic polyp."

Kahi and colleagues looked at more than 6000 colonoscopies.[4] They looked at what would be the normal or "best guess" average rate for detection of serrated lesions. They considered a benchmark for the standard minimum rate of adenoma detection of 25% for men and 15% for women. If you were one of the average adenoma detectors or high adenoma detectors meeting the benchmarks, they found that you should be finding approximately 4.5% proximal serrated lesions. This is not a new gold standard, but perhaps a number to keep in mind as you begin to monitor your performance in serrated polyp detection. That should be the approximate prevalence of proximal serrated lesions, in the proximal colon, above the sigmoid colon.

New Guidelines in Press

We are going to see new guidelines that include recommendations for management and follow-up of serrated polyps. A multisociety task force just submitted the final manuscript for the approval of the individual gastrointestinal societies, and it is expected to be available later this year.

In the meantime, you should follow a high-risk serrated adenoma with dysplasia or a large serrated adenoma as a high-risk adenoma at standard intervals -- typically a 3-year follow-up. A low-risk serrated lesion can be followed as a low-risk adenoma.

Look for Subtle Changes

Let us return to the original question. Are we to blame, or is biology to blame, for these interval cancers? Start looking at your colonoscopy technique. Think about these endoscopic identifiers. Look for subtle changes, such as obscured vasculature, mucous caps, peripheral rim debris or bubbles, alteration in the contour of the mucosal fold, or a dome-shaped protuberance These are things that all should be hallmarks, especially in the proximal colon.

Hopefully, we will have a major impact on interval cancer because we are not doing quite as well as we thought we were with screening colonoscopy. I hope this applies to your practice and gives you some tips to make a meaningful difference in your patients who are undergoing these screening examinations. I look forward to talking to you again. I am Dr. David Johnson; thanks for listening.