National clinical study

ctDNA Assessment of Large Rectal Polyps: An Observational Cohort Study

In this study, we will investigate the value of pre-operative circulating tumour DNA (ctDNA) as an alternative strategy to stratify the treatment of patients with large rectal polyps.

The project received funding in 2024.

Abstract

The optimal management of patients with large rectal polyps (≥ 2.5 cm) represents a signifi cant clinical challenge. Despite appearing macroscopically benign on endoscopic assessment, up to 30% of large rectal polyps are found to harbour early-stage rectal cancers. Several clinical investigations are currently used to try to diff erentiate these malignant rectal polyps from benign rectal polyps, including digital rectal examination (DRE), magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). However, the accuracy of these investigations is limited, and the fi nal diagnosis is often only made with a pathological assessment once the polyp has been removed.

There are two main approaches for removing large rectal polyps. The fi rst, and most simple, is endoscopic mucosal resection (EMR). This involves removing polyp along with the most superfi cial layer of the rectum and can be performed without general anaesthetic during a normal endoscopy. The second approach is transanal resection. This involves the use of specialized platforms inserted into the rectum under a general anaesthetic, which allow a full-thickness resection of the rectum wall. While EMR is a suffi cient treatment for benign polyps, it risks an incomplete (or R1) resection of malignant polyps, which may mandate further, and more extensive, surgery. Although transanal resections reduce the risk of R1 resection of malignant polyps, these procedures are only available at specialized centres, and are associated with greater costs and risks of complications than EMR. Currently available strategies to stratify patients with rectal polyps to EMR or transanal resection are not particularly robust. As a consequence, patients with malignant polyps risk being undertreated with EMR, whereas patients with benign polyps risk being overtreated with transanal resection.

In this study, we will investigate the value of pre-operative circulating tumour DNA (ctDNA) as an alternative strategy to stratify the treatment of patients with large rectal polyps. We hypothesise that ctDNA will be detectable in patients with malignant rectal polyps but not in those with benign polyps. In order to test this hypothesis, we will conduct a multicentre observational pilot study of 50 patients with large rectal polyps undergoing EMR or transanal resection. Blood samples for ctDNA analyses will be taken prior to surgery and correlated with the fi nal pathological result (benign or malignant polyp).

This study has the potential for a significant clinical impact. If our hypothesis is proven, an individual patient’s ctDNA status could be used to allocate them to either EMR (ctDNA negative) or transanal resection (ctDNA positive). This would lead to several benefi ts. First, it would reduce the risk of complications for patients with benign polyps, who could be treated exclusively with EMR. Second, it would reduce the number of patients with malignant polyps requiring completion surgery after EMR, as these patients could be allocated to and adequately treated with transanal resection. Finally, it would reduce the overall costs of treatment for this patient group, by reducing the number of patients requiring transanal resection or completion surgery. These impacts are not limited to Denmark but would be applicable to any nation where transanal resections are performed and ctDNA analyses are available.

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