Can individuals with colonic polyposis be managed safely with colonoscopic surveillance?

The eventual consequence faced by many individuals with one of the heritable colon polyposis syndromes is an elective colectomy. According to recent guidelines that address the management of familial adenomatous polyposis (FAP), attenuated FAP, or MUTYH-associated polyposis, the absolute indications for immediate colectomy include documented or suspected cancer or significant symptoms, and relative indications for colectomy include the presence of multiple adenomas > 6 mm, a significant increase in adenoma number, and inability to adequately survey the colon endoscopically because of multiple diminutive polyps [1]. With respect to FAP, these guidelines reflect the premise that colorectal cancer (CRC) is the inevitable outcome unless the colon is removed [2] [3]. Much of what we know about the natural history of FAP is derived from the St. Mark’s FAP registry in London, where the average age at cancer diagnosis was 39 years, with cancer developing in 93 % of patients by the age of 50 years [4].

The natural history is less well defined in other colon polyposis syndromes. In these cases, attempts at clearing colon polyps with colonoscopic polypectomy are typically recommended, and in situations where this is not feasible, colectomy is advised [1]. In individuals with serrated polyposis syndrome, serial endoscopic examinations with polypectomy are recommended, with surgical resection if the number or size of serrated polyps prohibits endoscopic polypectomy or if a cancer is diagnosed [5]. Clinical challenges in these situations include understanding the future cancer risk and the optimal treatment options, including timing of prophylactic colectomy.

Two articles in this issue of Endoscopy address this matter in further detail. The first is a retrospective review from three Japanese medical centers of 90 FAP patients with at least 100 colon adenomas and/or germline APC mutations [6]. These individuals, who all declined colectomy after being informed that this was the standard of care, were managed with colonoscopy and polypectomy by snare, endoscopic mucosal resection or endoscopic submucosal dissection every 3 – 6 months to remove all polyps ≥ 4 mm, followed by surveillance colonoscopy every 8 – 12 months. Patients (median age 29 years) were followed for a median of 5.1 years and underwent an average of eight colonoscopies with a median of 475 polyps removed per patient. A single endoscopist performed nearly all of the procedures, which included multiple 2-hour examinations, and the removal of > 1000 polyps in 16 patients. Although nearly 56 000 polyps were removed from this cohort, there were no adverse events related to polypectomy. Noninvasive cancer was found in five patients, all of whom were treated endoscopically without recurrence during follow-up. Only two patients in this cohort underwent colectomy, both for “dense polyposis.” The authors concluded that endoscopic surveillance of FAP is reasonable in the medium term in individuals who decline colectomy.

In the second study, 265 patients in the Spanish EPIPOLIP study were followed to assess their risk for CRC or prophylactic colectomy [7]. This cohort comprised individuals seen in high risk CRC clinics with at least 10 cumulative colon polyps of any histology, excluding those with FAP, Lynch syndrome, inflammatory bowel disease, or only hyperplastic rectal polyps. In addition, nearly 50 % of patients were excluded because of a diagnosis of CRC (28 %), prophylactic surgery during the first year (6 %), or insufficient data (13 %). The median age of the evaluable patients was 55.8 years, nearly twice the age of those in the Japanese study. Overall, 64 % had symptoms at diagnosis and 32.5 % had a first-degree relative with CRC. Patients were tracked for a median of 3.8 years, underwent a median of five colonoscopies, and had a median of 19 polyps removed. Ultimately, 17 patients (6.4 %) developed CRC and 15 patients (5.7 %) underwent prophylactic colectomy without a CRC diagnosis. The presence of symptoms at the time of the first colonoscopy was the only baseline variable independently associated with the development of CRC or the requirement for colectomy.

The Japanese study suggests that some selected individuals with FAP can be managed relatively safely, at least in the short term, with frequent colonoscopy with polypectomy. However, the follow-up in this study was short (5 years), and therefore conclusions about the medium or long term cancer incidence in those deferring colectomy could not be established. In addition, as the authors of this study point out, it is possible their FAP patients were at relatively low risk for CRC given their young age, lack of large adenomas or dense polyposis at baseline, and compliance with frequent colonoscopic examinations.

It is more difficult to form generalizations based on the results of the Spanish study. On the one hand, many of those with colon polyposis were presumably at relatively low risk given only 10 cumulative colon polyps were required for inclusion. However, the overall risk of cancer (6.4 % during follow-up) would be considered by many to be high compared with other cohorts found to have neoplasia at baseline screening colonoscopy. In the VA Cooperative Study 380, for example, only 0.8 % of patients with tubular adenomas > 1 cm at baseline and 1.2 % of patients with villous adenomas at baseline developed CRC within 5.5 years of follow-up [8]. Moreover, many patients were excluded from the Spanish analysis because of a cancer diagnosis within 1 year. The authors of this study suggest patients with > 10 neoplastic polyps require “frequent colonoscopies with short follow-up” and that more than 10 % will require colorectal surgery within 4 years.

Importantly, the individuals in the Spanish study were a diverse group in terms of cumulative polyp number, polyp histology, and polyp molecular/genetic background. This highlights the concept that individuals who develop multiple colorectal polyps are a genetically and clinically heterogeneous group [9]. Yet even in cases of FAP with the same APC mutation, there is striking variability between individuals with respect to phenotype and cancer risk [10]. For these reasons, development of evidence-based polyp surveillance guidelines and patient counseling about risk are especially challenging for those with colon polyposis.

While these studies do offer some reassurance about the feasibility of endoscopic management of patients with colon polyposis, the intensive procedural demands of the Japanese study, the relatively high cancer risk seen in the Spanish study, and the modest duration of follow-up should make us cautious about revising any current treatment guidelines. So what counsel should we provide to our patients with colon polyposis? First, based on our cumulative knowledge about colon polyposis syndromes, we should continue to stress that colectomy remains the treatment of choice for FAP or in any case of polyposis where endoscopic clearance of colon polyps is no longer achievable, as per current guidelines [1]. Second, chemoprevention with nonsteroidal anti-inflammatory drugs such as aspirin, sulindac, or celecoxib has been shown to reduce the colorectal polyp burden in polyposis syndromes, although their effect on preventing cancer in these patients is less clear [1] [2] [11]. Clinicians should emphasize that these medications are no substitute for colectomy, but they may make the strategy of colonoscopy and polypectomy more successful by reducing polyp size and/or number. For those who decline colectomy or for whom colectomy is not yet indicated, it appears that carefully selected cases can be managed with polypectomy in the short term. We agree with Ishikawa et al. and others that high risk patients who defer colectomy should be managed by expert endoscopists with the capacity to offer chromoendoscopy, endoscopic mucosal resection, and other advanced resection techniques in a setting that allows for lengthy procedures [6] [12]. Although the optimal colonoscopy surveillance interval for patients with FAP and other polyposis syndromes who decline colectomy has yet to be determined, it is important for clinicians to educate this patient population about their cancer risk as precisely as possible and to ensure that they understand the limited evidence regarding long term outcomes of endoscopic treatment.

• References

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