Adenoma risk score for surveillance of colorectal neoplasm – a step forward?

Colorectal cancer (CRC) is the third most common cancer worldwide, and accounts for 10 % of all malignancies and 8 % of cancer mortality [1]. Most colonic cancers arise from premalignant adenomatous polyps, and it has been assumed that the time taken for an adenoma to transform into carcinoma is about a decade. It seems logical, therefore, that the detection and removal of adenoma(s) is an opportunity for colonic cancer prevention. It is also well known that people who have undergone screening colonoscopy, and had adenomas removed during the screening process, also have an increased risk of developing adenoma(s) and CRC in the long term. To reduce the burden of CRC, various guidelines for surveillance have been published, and all guidelines recommend colonoscopy as the method of choice for surveillance of CRC.

The USA National Polyp Study observed a 70 % – 90 % lower than expected incidence of CRC in patients undergoing colonoscopic surveillance compared with three reference populations [2]. However, it is important to appreciate that colonoscopy is a relatively expensive and invasive procedure, with associated morbidity and limited availability.

Risk stratification of patients with adenoma for surveillance is based either on the number of detected adenomas or on the characteristics of the adenoma. Guidelines differ with regard to the interval of colonoscopy based on characteristics of the removed adenoma (number, size and histology, location). One significant difference between guidelines from the United Kingdom (UK) and those from the United States (US) is that the UK guidelines do not consider histological features and thus classify substantially more patients into a low risk category that entails a 5-year or no surveillance colonoscopy [3].

In a pooled analysis of seven prospective studies, Gupta et al. [4] concluded that the risk of metachronous advanced colorectal neoplasia (ACN) among individuals with 1 – 2 small adenomas varies according to readily available clinical characteristics, and ranges from as low as 2.9 % to as high as 12.2 %, depending on the specific risk factor and guideline used. The characteristics associated with a high risk of metachronous ACN were history of prior polyp(s) (12.2 %), villous histology (12.2 %), age ≥ 70 years (10.9 %), high grade dysplasia (10.9 %), any proximal adenoma (10.2 %), distal and proximal adenoma (10.8 %), and two adenomas (10.1 %). In an ideal model, determination of risk factors for ACN in patients with adenoma should take account of variables that relate to the patient, the pathological characteristics of the adenoma, and the epidemiological features.

In this issue of Endoscopy, van Heijningen et al. [5] report on their development and validation of a scoring system (adenoma risk score) for stratifying the risk of developing ACN. The system was based on follow-up of 2914 patients with adenoma(s) detected between 1988 and 2002 from 10 different hospitals reporting to the Dutch Pathology Registry. The model is based on independent predictors of ACN and appears logical and appealing as it incorporates both number (2 – 4 or ≥ 5 adenomas) as well as characteristics (size ≥ 10 mm, villous histology, proximal location) of index adenoma(s). The adenoma risk score appears to have a slightly better performance than the US/UK model (c-statistic 0.712 vs. 0.664/0.674). However, the discriminative ability of the adenoma risk score model had moderate performance for predicting ACN. Though the data were retrospective in nature and regular bootstrapping was used for analysis, it is important to appreciate that the calculation of absolute risk of ACN at 3 and 5 years was assessed based on adenoma risk score, age, and sex [5].

The adenoma detection rate (ADR) has been recommended as a quality benchmark and has been proposed as a reportable quality measure. Currently, ADRs ≥ 20 % in women and ≥ 30 % in men are recommended as quality indicator for colonoscopy [6]. Both increased awareness of the ADR as a quality measure, and advanced technology and techniques to enhance adenoma detection have led to an increase in ADRs. Absolute risk estimates by adenoma risk score based on patients with colonic adenomas up to 2002 may or may not hold true now for adenoma patients, and this model of risk stratification needs validation based on contemporary studies utilizing modern technology for detecting colonic adenomas. Moreover, patients with a history of polyps are known to have a significantly higher ADR when compared with average risk individuals. Defining a minimum target ADR for individuals with a history of polyps undergoing surveillance colonoscopy is important [7].

Advanced neoplasia is an important target of colorectal screening and surveillance, and this risk estimate may help to inform the decision process, both for the individual patient and for the public health community. Colonoscopy, whether for diagnostic, screening or surveillance purposes, is associated with a reduction in CRC incidence and CRC mortality. However, the data regarding their impact on overall mortality are much more limited at the present time [8]. The adenoma risk score model developed by van Heijningen et al. [5] gives an estimate of absolute risk of ACN at 3 and 5 years but the decision on timing of surveillance colonoscopy, based on risk estimate, depended on the physician, as it did not take into account the time interval of the next surveillance colonoscopy.

It is important to point out that despite the efforts of van Heijningen et al. [5] and other investigators, postpolypectomy risk stratification is in a stage of development. Ideally, a risk model should be theory based, utilize continuous variables rather than arbitrarily defined cutoffs, and be derived and subsequently validated in distinct patients. A discrepancy between the guidelines and clinical practice for surveillance after polypectomy still exists. Many patients receive either no or inappropriate surveillance, in particular with shorter intervals than recommended. This unbalanced utilization of surveillance negatively affects cost-effectiveness and resource utilization, and results in unnecessary risk of complications. A surveillance program based on adaptability, feasibility, and acceptability in clinical practice, and one that has an impact on morbidity and overall survival needs to be established. By combining data from clinical trials and ACN risk models, we can provide clinicians with better tools to efficiently target care to individual patients.

In the pursuit of determining ideal and efficient risk stratification for colonic adenoma, the study by van Heijningen et al. [5] is a small but important advancement. However, we are certain that this is not the last word in this regard, and that more efficient predictive models of risk stratification will be forthcoming in the near future.

• References

• 1 Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: source, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-386
• 2 Winawer S, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329: 1977-1981
• 3 Martínez ME, Thompson P, Messer K et al. One-year risk of advanced colorectal neoplasia: United States vs. United Kingdom risk-stratification guidelines. Ann Intern Med 2012; 157: 856-864
• 4 Gupta S, Jacobs ET, Baron JA et al. Risk stratification of individuals with low-risk colorectal adenomas using clinical characteristics: a pooled analysis. Gut 2015; DOI: 10.1136/gutjnl-2015-310196.
• 5 van Heijningen EM, Lansdorp-Vogelaar I, van Hees F et al. Developing a score chart to improve risk stratification of patients with colorectal adenoma. Endoscopy 2016; 48: 563-570
• 6 Rex DK, Schoenfeld PS, Cohen J et al. Quality indicators for colonoscopy. Gastrointest Endosc 2015; 81: 31-53
• 7 Sanaka MR, Rai T, Navaneethan U et al. Adenoma detection rate in high-risk patients differs from that in average-risk patients. Gastrointest Endosc 2016; 83: 172-178
• 8 Lin OS, Kozarek RA, Cha JM. Impact of sigmoidoscopy and colonoscopy on colorectal cancer incidence and mortality: an evidence-based review of published prospective and retrospective studies. Intest Res 2014; 12: 268-274