Using data pooled from four prospective studies with one-year post-polypectomy follow-up, we found that the estimated risk of advanced colorectal neoplasia, as well as of HGD/colorectal cancer, increased across risk categories for both the U.S. and U.K. surveillance guidelines. Risk estimates in the lowest risk groups were similar between the two sets of guidelines; however, the U.K. guidelines do not consider histological features and thus classify substantially more patients into a low-risk category that entails a five-year or no surveillance colonoscopy. Patients classified as high-risk by the U.K. criteria (≥ 5 small adenomas or ≥3 adenomas with at least one ≥1cm) comprised 12.1% of the total population and had an 18.7% absolute risk of advanced neoplasia at one year, substantially higher than that of the U.S. higher-risk group; the U.K. criteria recommend a single one-year clearing colonoscopy for these patients rather than waiting for three years. We estimated that the net result of applying the U.K. criteria rather than the U.S. criteria to a population comparable to the one we studied would confer clinical benefit (two-year earlier detection of advanced adenomas) for 19% of patients that harbor these lesions at one year at a net cost of 0.03 additional colonoscopies per five years for all followed patients.
The U.S. surveillance guidelines have been informed by controlled trials of surveillance intervals. In particular, the NPS reported that the yield of advanced neoplasia in patients with three-year surveillance colonoscopy only did not differ from patients with both one and three-year colonoscopy (18
). NPS investigators concluded that the first follow-up colonoscopy can safely be delayed in most patients for up to three years. However, the NPS also identified a subgroup of patients at substantially increased risk at one year (those with ≥ 3 adenomas at baseline), and also suggested that there is a low-risk group for which a much longer interval might suffice. Our study results generally agree with these observations.
An optimal colonoscopy surveillance program would prevent colorectal cancer mortality using the most cost-effective follow-up protocol. Substantial evidence indicates that many U.S. physicians frequently advise patients to have surveillance exams at shorter intervals than proposed by the guidelines (19
). These reports illustrate the need for evidenced-based risk criteria to better inform physicians and improve adherence to guidelines (9
). Data that reliably identify subsets of patients at high- and low-risk for clinically important interval lesions may provide needed assurance to the endoscopists about the appropriateness of guidelines. Risk of advanced neoplasia at one year was low for both the U.K. and U.S. low-risk groups (4.4% and 3.8%, respectively), both of which allow at most two small adenomas. However, the U.S. lower-risk group excludes patients with villous adenomas or HGD who would be classified as U.K. low-risk. The recently-adopted European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis (25
) suggest that programs may wish to consider adenoma histology in the risk classification of the low/intermediate risk groups. However, imperfect agreement within and between pathologists in classifying villous histology and degree of dysplasia (26
) may limit the value of this approach. We found that patients whose adenomas had villous histology or HGD and were reclassified into the U.S. higher-risk group from the U.K. low-risk group had a greater risk of advanced neoplasia than those who remained in the U.K. low-risk group. These results suggest information on histology and HGD provide additional, though modest discrimination between lower- and higher-risk patients. A better understanding of this discrimination by use of quantitative biological markers that capture the underlying biology is warranted for further refining risk stratification.
While we cannot know with certainty why advanced neoplasms were detected at the one-year surveillance colonoscopies in our study patients, most of these lesions were plausibly missed or below the limits of detection at the previous exam. If this assumption is correct, the quality of the prior colonoscopy may be the principal determinate of one-year advanced colorectal neoplasia, and high-risk patients, because of large or numerous polyps, may especially benefit from improved colonoscopy quality. In fact, the 2012 U.S. surveillance guidelines place emphasis on a high-quality baseline colonoscopy, as this minimizes the risk of missed lesions (9
); this is an important consideration since lack of removal of all polyps at prior colonoscopy is associated with higher risk of developing colorectal cancer (28
). Wide variation in adenoma detection rates among endoscopists has also been shown to be associated with risk of interval cancers, especially when the detection rates fall below 20% (29
). Improvements in our understanding of the biology and histological heterogeneity of colorectal polyps (30
), advances in endoscopy techniques (32
), and improvements in colonoscopy quality are likely to lead to fewer missed lesions and higher adenoma detection rates (33
Strengths of our study include its prospective design, the large population of patients with scheduled one-year colonoscopies, pooling of patient-level data, and direct comparison of two sets of surveillance guidelines on the same patients. However, the relatively small number of patients with HGD or invasive colorectal cancer at one year limited our ability to compare risk estimates for these rare endpoints. Data were not collected on colonoscopy quality measures such as withdrawal time, caecal intubation, and endoscopists’ adenoma-detection rates; thus, we could not determine the extent to which variation in colonoscopy quality accounted for the findings of advanced neoplasms at the one-year colonoscopy. The baseline colonoscopies for this study were performed between 1984 and 1998; arguably colonoscopic technique and quality have changed since that time. Nevertheless, rates of detection of advanced neoplasia at one year did not appear to vary by study date. Thus, in spite of recent improvement in endoscopy quality, relative differences between U.S. and U.K. criteria are likely to persist. Our study population represents patients enrolled in prevention trials, and their risk distribution may not be representative of the general population. However, variation in risk among trials was modest, and less than the variation between risk groups as defined by both the U.K and the U.S. criteria.
In conclusion, our results suggest that the U.K. guidelines identify a subset of high-risk patients who would benefit from a one-year clearing colonoscopy without substantially increasing the overall rate of surveillance colonoscopies. Further study of the effectiveness of including histology in the U.K. criteria is warranted, particularly for patients with low-risk adenomas. Advanced neoplasia is an important target of colorectal screening and surveillance, and these risk estimates may help to inform the decision process, for both the individual patient and the public health community.