Safety of endoscopic mucosal resection of large colonic polyps in elderly patients: a systematic review and meta-analysis

Introduction

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. In the year 2020, it was estimated that there were more than 1.9 million new cases of CRC occurring globally, while 935,000 deaths were attributed to CRC, representing about 1 in 10 cancer cases and deaths. Overall, CRC ranked third in terms of cancer incidence, but second in terms of cancer mortality in 2020 [1]. The incidence of CRC increases rapidly with age, with rates of 90.2 per 100,000 population in individuals aged 60-64 years, 121.4 per 100,000 population in people aged between 65 and 69, while for those aged 85 years and older, the rate is as high as 258.8 per 100,000 population [2]. Most commonly, CRC arises from pre-cancerous polyps that transform into CRC over time [3]. The prevalence of adenomas also increases with age [4], and the transformation of adenomas to CRC occurrs more rapidly in elderly patients [5], probably secondary to accumulated mutations. The size of the polyps is an independent predictive factor for dysplasia, with larger polyps having a higher risk of advanced dysplasia and CRC [6]. Therefore, elderly people with large size polyps are a population that has a high risk of developing CRC.

Early colorectal polyp detection and resection are necessary to improve the CRC survival rate [7]. Small adenomas can be completely removed using biopsy forceps, but larger adenomas require snare resection (with or without electrocautery) or advanced endoscopic resection techniques, such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) [8]. Although EMR has been widely used for removing large polyps, there are limited studies regarding its safety in very elderly patients with large polyps. We conducted a systematic review and meta-analysis of the available literature to evaluate the safety and efficacy of EMR in large colorectal lesions (>20 mm) in elderly patients over 75 years of age.

Materials and methods

We searched the following databases from inception to August 4^th, 2021: MEDLINE (PubMed), Embase (Embase.com), Cochrane Central Register of Controlled Trials (Wiley Cochrane Library), and Web of Science Core Collection (Clarivate Web of Science). A search strategy combining truncated keyword and subject terminology for endoscopic mucosal resection of large polyps in the elderly was developed for Embase by an experienced health science librarian (WL-S) and the vocabulary and syntax were translated for the remaining databases. We defined a large polyp as ≥20 mm in size. Database age filters were used when present, and exclusively non-human studies were eliminated. Publication and study type limits were used to exclude editorial materials, commentaries, reviews, guidelines, case reports, and previous systematic reviews and meta-analyses, in order to locate only clinical studies. No language or publication date limits were imposed. Full search terms are available in the Supplementary material. Results were exported to EndNote 20 (Clarivate) and were deduplicated by software algorithms with visual inspection. Data was abstracted by 2 authors (UI and AN) independently. Quality assessment of the studies was performed using the Newcastle-Ottawa quality assessment score, also by 2 authors independently. The quality of the study did not interfere with its inclusion in the meta-analysis. Our primary outcome was to evaluate the risk of polypectomy bleeding and perforation. This meta-analysis was performed in accordance with PRISMA guidelines [9].

Results

Our initial search identified 1060 articles, of which 6 observational studies with 2903 patients were included in the meta-analysis [10-15]. Fig. 1 elaborates the systematic literature search of our study. Baseline characteristic of patients, including the size of polyps, their location and histological findings, are reported in Table 1. All studies were rated as good quality. There were 2 studies that compared outcomes of EMR between patients older and younger than 80 years [11,12]. One study reported the outcomes of EMR in patients over 75 years of age, and one reported outcomes in patients over 80 years of age without a comparative group [10,14]. Two studies compared outcomes in patients older and younger than 75 years [13,15].

Figure 1 Literature review process

Table 1 Baseline characteristic of the included studies

In patients over 75 years of age, pooled rates (95%CI) for post-polypectomy bleeding were 5.3% (2.3-11.7%), I²=73.7%; and perforation was 1.9% (0.9-3.8%), I²=0% (Fig. 2,3). In a subgroup analysis including patients over 80 years of age, the pooled rate (95%CI) of post-polypectomy bleeding was 2.4% (1.2-4.8%), I²=0; and perforation was 2.1% (0.7-5.8%), I²=18.6%. There was no statistically significant difference in the risk of post-polypectomy bleeding (OR 0.922, 95%CI 0.359-2.367, I²=0) and perforation (OR 1.066, 95%CI 0.188-6.031, I²=0) between patients over 80 years of age and younger patients. Among patients over 80 years of age who underwent follow-up colonoscopy for surveillance, the pooled rate (95%CI) of residual polyps or recurrent polyps was 25% (17-35.3%), I²=59.5%. Rates of residual or recurrent polyps were significantly higher in patients over 80 years of age compared to younger patients (OR 2.234, 95%CI 1.549-3.223, I²=0). There were 14 deaths reported in the included studies. None was reported to be directly secondary to the procedural complications. Among the reported causes of death, 2 patients under 80 years of age died of colorectal cancer during a median follow up of 32.5 months, while 2 patients died of cardiac causes. There was no publication bias as assessed by funnel plot diagram (Fig. 4).

Figure 2 Pooled rate of post-polypectomy bleeding in patients over 75 years of age

Figure 3 Pooled rate of perforation in patients over 75 years of age

Figure 4 Funnel plot for post-polypectomy bleeding over 75 years of age

Discussion

It is established that endoscopic screening and resections of colorectal polyps decrease the incidence of CRC, and there is a large body of evidence to support the utility of colonoscopy in elderly patients [7,16-18]. Large polyps have a greater risk of harboring invasive carcinoma [6,19]. Resection of large polyps during endoscopy raises a few concerns, including the adverse events related to the procedure and the possibility of inadequate resection. Nevertheless, EMR is an effective technique for resection of polyps. It is imperative to consider the safety of EMR in elderly patients with large polyps, as this population has a greater incidence, as well as a higher transformation rate of polyps to dysplasia, but there is also concern regarding adverse events related to the procedure, due to comorbidities, and potential longevity [4,5].

The 2 major complications related to the endoscopic removal of large colon polyps are delayed bleeding and perforation. Studies have reported bleeding rates following EMR of large polyps in the range 2-11% [20-26]. In our meta-analysis, we found that the pooled risk for post-polypectomy bleeding was 5.3% (95%CI 2.3-11.7%) in patients over the age of 75, while the pooled risk for post-polypectomy bleeding in patients over 80 years of age was 2.4% (95%CI 1.2-4.8%). We found no statistically significant difference in post-polypectomy bleeding in patients over 80 years of age compared to the younger population. Bronsgeest et al did not find significantly more bleeding complications in elderly patients over 75 years of age, but observed that bleeding complications were more frequently observed when antithrombotic drugs were used, especially in patients who were on dual antiplatelet therapy [13]. Perforation is also one of the most dreaded complications of EMR, as it can result in peritonitis and morbidity. EMR-related perforation has been reported with a rate between 0% and 3% in earlier studies [22,25,27-29]. In our meta-analysis, we found that, in patients over the age of 75, the pooled risk for perforation was 1.9%, whereas in patients over 80 years of age it was 2.1%; again there was no statistically significant difference in the risk of perforation between patients over 80 years of age and the younger population.

The residual polyp or recurrence rate after EMR has been reported in the literature to be between 4% and 40% [20,22,30-35]. In our study this rate was 25% (95%CI 17-35.3%) in patients over 80 years of age. The biggest risk factor for recurrence after EMR is piecemeal resection. It is well documented that en bloc resection is associated with a lower residual rate compared to piecemeal resection. Follow-up examination after endoscopic removal of large polyps is essential to decrease recurrence and to detect residual tissue [35-38]. The follow-up timeline is based on the histology and resection method. After piecemeal resection, follow up is usually recommended after 6 months [8]. Gomez et al reported residual polyps in 22 of 70 patients who underwent follow-up colonoscopy. A piecemeal technique was utilized in 20 of 22 patients who had residual polypoid tissue. ESD is associated with a lower rate of recurrence as compared to EMR, but ESD is a labor-intensive and technically difficult procedure associated with a higher perforation rate [39].

Global life expectancy is increasing, and the aging population and the increased implementation of screening programs will lead to a higher rate of detection of large polyps in the elderly population. Surgical removal of adenoma in this population is associated with significant morbidity and mortality [40]. EMR appears to be a safer option, as it is less invasive, usually does not require general anesthesia, and is conducted in an outpatient setting. EMR in the elderly population with large polyps is also not associated with an increased risk of bleeding or perforation. Efforts should be made towards increased surveillance and resection of polyps in the elderly, as it will decrease CRC morbidity and mortality. The role of distal attachment devices has recently attracted growing interest as a means to improve the detection of colonic adenomas. A recent network meta-analysis showed only a modest increase in the rate of detection of colonic adenomas with the use of distal attachment devices, with no device showing any advantage over another [41].

To our knowledge, this is the first systematic review and meta-analysis conducted to evaluate the safety of EMR in elderly patients. There are several strengths to our study. We included all the current studies to date that focused on evaluating the safety of EMR for resection of colonic polyps >20 mm in patients over 75 years of age, and the number of patients included in the final meta-analysis was reasonable to evaluate differences in outcomes. We performed further subgroup analyses to evaluate differences in outcomes in patients over 80 years of age compared to the younger population. However, there are some limitations to our meta-analysis results. All the included studies are non-randomized observational studies that might have included bias in the study results; therefore, large prospective trials are needed to evaluate the safety of EMR in elderly patients. One study was in abstract form and has not yet been published in full [15]. Given the lack of data reporting in all studies, we unable to evaluate differences in the rate of en bloc resection in the elderly population compared to younger patients, or to assess differences in all-cause mortality.

In summary, EMR is safe in elderly patients and is not associated with a greater risk of complications compared to the younger population. Our study revealed higher odds of residual polyp in patients over 80 years of age. Therefore, efforts should be made to carry out adequate surveillance of polyps with colonoscopy in these elderly patients, to decrease the morbidity and mortality associated with colorectal cancer. Further larger prospective trials are needed to evaluate the safety of EMR in very elderly patients.