Identifying the low-risk population for metachronous colorectal neoplasia: a first step towards personalized surveillance

Colorectal cancer (CRC) is the third most common cancer, and it is a major cause of cancer-related deaths worldwide [1]. Surgery remains the standard method for curative treatment of CRC. However, after patients with CRC undergo surgical resection, their risk of developing metachronous CRC in the remaining colorectum is higher than that of the average-risk population. The cumulative incidence of metachronous CRC is reported to be approximately 0.3 % per year [2]. Postoperative surveillance colonoscopy plays a pivotal role in the early detection of recurrent CRC at a curable stage, as well as in the detection and removal of metachronous precursor lesions, which may contribute to reducing the incidence of and death from metachronous CRC [3].

The US Multi-Society Task Force guideline published in 2016 and the recently published European Society of Gastrointestinal Endoscopy and European Society of Digestive Oncology guideline recommend that the first surveillance colonoscopy should be performed 1 year after CRC surgery, the second colonoscopy 3 years later, and the third 5 years after the second [3] [4]. According to a recent meta-analysis of endoscopic surveillance studies, the risk of recurrent and metachronous CRC after surgery is highest during the 36-month period after surgery, after which it significantly decreases [5]. This suggests that metachronous CRC after surgery may originate from incompletely resected or missed lesions. The need for surveillance colonoscopy at 1 year after CRC surgery is obvious, but the evidence supporting the timing of subsequent surveillance examinations is weak. Although there is a growing body of literature on the risk factors for metachronous neoplasia, the same surveillance schedule is recommended for all CRC patients because the current guidelines do not provide a risk stratification.

“Considering that the incidence of metachronous CRC decreases significantly after 3 years postoperatively, intensive surveillance in low-risk patients is not cost-effective and may increase the risks associated with colonoscopy procedures.”

In this issue of Endoscopy, Frazzoni et al. report the results of a predictive model for identifying the low-risk population for metachronous colorectal neoplasia after CRC surgery [6]. At the second surveillance colonoscopy, performed 4 years after surgery, the incidence of metachronous neoplasia was approximately 27 %. A history of left-sided colon cancer, one or more advanced adenoma at the index colonoscopy, and one or more adenoma at the first surveillance colonoscopy were found to be risk factors for metachronous neoplasia. In their model, the second surveillance colonoscopy could be omitted, with a sensitivity and negative predictive value both around 80 % – 90 %, in low-risk patients without these risk factors.

An ideal postoperative surveillance schedule would reduce the risk of death from CRC by enabling the timely detection and removal of metachronous precancerous lesions, while minimizing the potential harm of colonoscopy. Therefore, establishing a personalized surveillance schedule is of the utmost importance. The risk of developing metachronous neoplasia should be calculated at the level of individual patients, taking into account the epidemiological factors associated with metachronous lesions after CRC surgery. Although various risk factors for metachronous CRC have been identified, there is a lack of data on risk stratification through optimized combinations of risk factors. Frazzoni et al. attempted to stratify the risk of developing metachronous lesions in patients after CRC surgery, using three risk factors for metachronous lesions consistent with the previous literature. The risk-stratification model proposed by the authors is simple and easy to implement in clinical practice. Although they developed a predictive model, they suggest that patients classified as low risk could safely skip the second surveillance colonoscopy. Considering that the incidence of metachronous CRC decreases significantly after 3 years postoperatively, intensive surveillance in low-risk patients is not cost-effective and may increase the risks associated with colonoscopy procedures. Increasing the surveillance interval for low-risk patients is highly important to minimize the overutilization and potential harm of colonoscopy and overall medical expenditures. The findings presented by Frazzoni et al. provide new insights into an appropriate surveillance colonoscopy schedule for low-risk patients.

Furthermore, the quality of colonoscopy is an issue that must be addressed. Although colonoscopy is a standard tool for the early detection and prevention of metachronous CRC, it is not perfect. A considerable number of post-colonoscopy CRCs arise from missed cancers and missed or incompletely resected benign lesions [7]. In other words, metachronous CRCs found in the second surveillance colonoscopy are likely to be lesions that were missed or incompletely resected at the first surveillance colonoscopy. If the quality of perioperative colonoscopy and the first surveillance colonoscopy is poor, the clinical implications of the findings reported by Frazzoni et al. in terms of risk stratification for metachronous lesions will be greatly diminished, and a reduction in CRC-related deaths may not be achieved. Therefore, the importance of the quality of the first surveillance colonoscopy after surgery cannot be overemphasized, as it may determine the prognosis of CRC patients.

Ultimately, to establish a personalized postoperative surveillance colonoscopy schedule that reduces death from metachronous CRC while minimizing the overuse of colonoscopy, large-scale prospective cohort studies with standardized patient data, colonoscopy quality, and surveillance intervals are needed. Several prospective studies in progress are expected to provide a solution to this issue.

• References

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• 3 Hassan C, Wysocki PT, Fuccio L. et al. Endoscopic surveillance after surgical or endoscopic resection for colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Digestive Oncology (ESDO) Guideline. Endoscopy 2019; 51: 266-277
• 4 Kahi CJ, Boland CR, Dominitz JA. et al. Colonoscopy surveillance after colorectal cancer resection: recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2016; 150: 758-768.e11
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