Diminutive polyps and future colorectal cancer risk perception: how low do we need to go?Referring to von Renteln D et al. p. 221–229
26 February 2018 (online)
As cost-efficiency pressures weigh increasingly on healthcare systems, it is important to question current practice and the evidence upon which our practice is based. Before instituting a randomized controlled trial (RCT) to categorically clarify whether diminutive polyps (≤ 5 mm) can be safely left in situ at colonoscopy, we need evidence to reassure physicians, patients, and regulatory agencies that such a study would be ethical and acceptable.
“We might consider as an endoscopic community whether we want to go for no intervention in these lowest risk lesions, or whether the advantages and security of resection and pathology are balanced by the small risks and cost of cold resection.”
In this month’s issue of Endoscopy, von Renteln and colleagues present the argument that it is safe to defer resection of diminutive lesions and have examined the valuable question of whether patients would find such a practice acceptable . This prospective multicenter study was undertaken in Canada and the USA and involved patients at teaching hospitals who were awaiting colonoscopy. The majority of these patients were well-educated and had undergone a previous colonoscopy. Of the 557 eligible patients who completed the survey, half (95 % confidence interval 46 % – 55 %) were found to be willing for their diminutive polyps to be left in situ and reassessed or removed at a subsequent surveillance procedure within an RCT. Higher levels of education were associated with increasing willingness to accept deferred removal. This provides invaluable data for the setting up of such an RCT.
Certainly the idea behind this study is clinically relevant. The histological assessment of polyps is both time-consuming and costly, as are equipment costs. Undertaking polypectomy carries a finite risk, although it is extremely low in diminutive polyps, which can usually be removed by cold snare. There are also some data to suggest that these small polyps generally have a low rate of progression to advanced lesions (3.7 % – 4.2 % per annum) , although caution must be taken when interpreting data that is estimated and retrospective. A Japanese group did undertake a prospective study of 225 diminutive polyps (without morphological features of concern), which were marked and followed up with colonoscopic surveillance over a mean period of 7.8 years . During this study period, only one polyp grew to 10 mm and only one progressed to high grade dysplasia; none progressed to adenocarcinoma.
The European Society of Gastrointestinal Endoscopy (ESGE) recommends that diminutive lesions are removed by cold snare, a relatively inexpensive technique that provides high rates of complete resection with low complication rates , but allows diminutive lesions in the rectum and sigmoid (that are felt with high confidence to be hyperplastic) to be left in situ. Therefore, there are already, in some countries, policies in place to leave some diminutive polyps behind. It must also be remembered that a 10-fold variability in the number of adenomas detected per patient exists between endoscopists, meaning we accept a proportion of endoscopists already leave some adenomas in situ . Given the good safety profile for removing polyps of < 5 mm, it raises the question of how appropriate it is to delay removal when the chances of complete removal decrease and the risks of removal increase as the polyp increases in size. In addition, this relies on the patient being offered and returning for further surveillance.
Current surveillance guidelines depend on the histology of the removed polyp as many are based on the histological classification (adenoma or not, presence of villous adenoma), the degree of dysplasia seen by the histopathologist, as well as the total number of polyps removed. Surveillance strategies for adenomatous polyps as opposed to serrated polyps also differ . The low risk nature of these diminutive polyps has already been taken into account in many surveillance protocols, where patients will often no longer require surveillance following the resection of one to two diminutive polyps.
The study by von Renteln et al. was undertaken in Northern America, where the current guidelines recommend that all identified polyps be removed and where financial reimbursement often relates to the therapeutic procedures performed and associated pathological analysis. The data from well-educated patients taking part in research in academic centers may not be translatable to the general population, who will not necessarily be offered further surveillance or may fail to attend if they are. Their proposed policy might also be hard to implement in a system where, not only the patient, but also the pathologist and physician may oppose the change, especially if there is a perceived or actual medicolegal risk.
If our understanding of the progression rates of adenomas is limited, our understanding of the progression of serrated polyps within the colon is even sparser. The ability of endoscopists to assess polyp risk is limited. Areas of depression (Paris 0-IIc) are considered a high risk feature; however, Western experts have only moderate agreement using the Paris classification, with a kappa of 0.42 and worse figures for diminutive lesions . Some polyps appear genetically “born to be bad” and develop rapidly to cancer; although these are probably rare, they may be hard to identify endoscopically . Sessile serrated lesions with dysplasia may be misclassified as small adenomas and these are thought to be aggressive high risk lesions that might well become cancer prior to the next surveillance.
The strongest concern about a potential policy to leave diminutive polyps in situ is that there is good evidence that each 1 % absolute increase in adenoma detection rate (ADR) is associated with a 3 % relative decrease in the risk of colorectal cancer for the patient . These data come from the evaluation of 314 872 colonoscopies and looked at the development of colorectal cancer 6 months to 10 years following colonoscopy; the risk of interval cancer decreased in a linear manner with increasing ADR, without evidence of any threshold. Because endoscopists with high ADRs are presumably those who identify and remove even the smallest of polyps, this suggests improved cancer protection with removal. It remains to be seen, however, whether it is the ADR with resection that is preventative, or whether this is simply a reflection of more comprehensive mucosal surveillance for significant lesions.
Perhaps a “resect and discard” strategy would be a more preferable middle-ground strategy. This would save costs by decreasing the need for histopathological assessment, although the equipment and time for polypectomy would still be needed. This discard strategy is only recommended following optical biopsy by individuals who have > 90 % agreement between their optical diagnosis and subsequent histopathological assessment, which may be challenging to achieve for all endoscopists, though possible for some  . A simplified DISCARD-lite protocol has also been suggested, where only diminutive polyps in the rectum and sigmoid (which are usually hyperplastic rather than serrated) are characterized and selectively resected, while all others proximal to the rectosigmoid are assumed to be neoplastic, and are removed and discarded without assessment .
When taking this study further, consideration will have to be given as to how best to quantify specific patient risk e. g. family history of colorectal cancer, age, the presence of familial or attenuated polyposis syndromes, or the different risk in screening, fecal occult blood test (FOBT)-positive, populations (where the risk of advanced pathology or cancer in polyps is higher). The ADR would be impacted, unless photographic evidence were to be permitted, although this might introduce the possibility of gaming this key performance indicator. Small polyps may not be found on a subsequent procedure and, if tattoo labelling is proposed, it might theoretically impact on the biology of the marked polyp. Research and validation of how best to present risk to patients in this context would also be needed to ensure valid informed consent.
von Renteln and colleagues are to be congratulated on this important step toward a formal trial of leaving polyps in situ, but theirs is very much a first step with many issues outstanding. We might consider as an endoscopic community whether we want to go for no intervention in these lowest risk lesions, or whether the advantages and security of resection and pathology are balanced by the small risks and cost of cold resection.
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