The incidence of colorectal carcinoma can be significantly reduced by colonoscopic polypectomy and subsequent follow up.3–6
Periodic surveillance examinations have been prompted by the high frequency (30–60%) of adenomatous polyps detected at follow up4,7,20–24
compared with an incidence rate of approximately 16% at three years found in patients with no abnormalities at the index colonoscopy.25
Thus patients with a clean colon after initial polypectomy are believed to have a higher risk of developing metachronous adenomas or carcinomas than non-polyp carriers.
In accordance with the adenoma-carcinoma sequence, adenomas are recognised as precursor lesions of the vast majority of colorectal cancers.1,2
Several large studies carried out in recent years have identified the major factors determining the risk of developing high grade dysplasia and invasive carcinoma in an adenoma as tumour size and the amount of villous structure.10–13,26,27
An important question is whether these adenoma characteristics found at the initial examination can also predict the risk of metachronous adenomas and hence help in planning surveillance strategies.
Multiplicity of initial lesions was the first factor to be used as a suitable basis for scheduling different follow up intervals. Patients with multiple adenomas were re-examined every two years and patients with a single adenoma every four years, in accordance with their different risks of developing metachronous lesions.7
Recently, a number of studies have proposed extending the follow up interval,6,9,28
in particular for patients with a very low risk of developing metachronous adenomas or carcinomas. A retrospective study from St Mark's Hospital, London, UK, found that patients with only a single small (<10 mm) tubular adenoma detected in the rectosigmoid were not at increased risk of subsequent colon cancer, and that surveillance may therefore be of no value in these patients.29
The King's Fund consensus panel in London then concluded that follow up should not be recommended for patients with a single small tubular rectal adenoma or patients over 75 years of age.30
The Polyp Prevention Study Group concluded that patients with one or two tubular adenomas constitute a low risk group for whom follow up might be extended beyond three years.28,31
The National Polyp Study (NPS) recently focused on differentiation of low and high risk patients, and modified its recommendations accordingly.32,33
A three year interval for screening colonoscopy is recommended for patients with multiple adenomas (especially three or more) at initial colonoscopy, and for those with a parental history of colorectal carcinoma and aged at least 60 years at the initial diagnosis. A six year or longer surveillance interval is recommended for adenoma patients with one or two adenomas and a negative family history of colorectal carcinoma, provided that all polyps detected initially were removed and total colonoscopy was performed.33
The different risk groups are defined by the number of initial lesions, the patient's age, and family history. Several studies have shown that patients with a family history of colorectal carcinoma are at increased risk of developing adenomatous polyps.34–36
However, the hypothesis that a history of colorectal carcinoma in any first degree relative increases an individual's risk of developing adenomas has not been supported by other studies.37,38
Conversely, siblings and parents of patients with adenomatous polyps have been reported to be at increased risk of colorectal carcinoma.39
In our study, a positive parental history of colorectal carcinoma proved to be a significant prognostic factor for the development of metachronous adenomas. However, the size of the largest initial lesion and villous structure were also of prognostic significance. These differences may be due to differences between the NPS samples and that of the Erlangen Registry in terms of the nature of the initial lesions and patient characteristics. The sample (NPS) included significantly more male patients (p=0.003), more patients older than 60 years (p<0.0001), fewer large adenomas (p=0.0001), and a larger number of tubular than tubulovillous or villous adenomas (p<0.0001). No significant differences in the distribution of low and high grade dysplasia were found between the samples (p=0.22).
Different conclusions may also result from different statistical methods applied. No publication has so far considered the problem of interval censored observations with respect to the event of interest. The transition to advanced pathology—that is, progress in the adenoma-carcinoma sequence—cannot be observed directly. It is only possible to register an existing state by inspection. Many authors apply classical standard methodology, such as Cox regression, to calculate relative risks. The use of Cox regression or Kaplan-Meier estimates for truly interval censored data results in over long surveillance intervals. For determination of follow up intervals, we calculated 5%, 10%, and 20% quantiles of patients with metachronous adenomas of advanced pathology. The 10% quantile provided the best differentiation between high and low risk patients. Applying the 5% quantile would have led to a very short interval (six months) for high risk patients and the 20% quantile would not have provided different risk related intervals (which was the intention of the study) for the two groups. Additionally, this cut off point may also be appropriate in terms of cost effectiveness. The following recommendations are therefore based on the 10% quantile.
In our view, the possibility that some of the adenomas found at follow up may be missed polyps40–42
and not true metachronous adenomas is of no relevance for the calculation of clinical surveillance recommendations.
The results of the multivariate analysis of time intervals for the detection of advanced metachronous adenomas form the basis of our follow up recommendations. We distinguish two degrees of risk for the development of advanced metachronous adenomas: low risk and high risk. Patients with a low risk—that is, no parental history of colorectal carcinoma and only single or small (≤10 mm) tubular adenomas at the initial clearing—can safely wait 10 years for their first surveillance examination. Patients with a high risk of developing metachronous adenomas of advanced pathology—that is, all other patients—should have their first follow up examination no later than three years after the initial clearing.
All surveillance examinations should be performed as complete colonoscopies up to the caecum because of the high rate of metachronous adenomas located in the right colon.43
Surveillance programmes should be centralised at regional computerised registries so as to reliably ensure that patients are reminded to attend for the re-examination, even after 10 years.