Recurrences after standard EMR vs plus thermal ablation EMR of advanced sessile and lateral spreading colorectal adenoma: a multicenter, randomized controlled trial

Colorectal cancer (CRC) is the third most common cancer in men and the second
in women worldwide [1]. In Western societies, approximately 40% of all CRC
patients die within the first five years of the disease [2]. CRC predominately
develops from premalignant polypoid lesions of the colon. Colonoscopy with
polypectomy is able to detect and subsequently remove these (pre)malignant
lesions and thus reducing the incidence and mortality of CRC [3]. In order to
achieve this in an early stage before the polyps become invasive, a national
colorectal cancer screening program is implemented in various countries [4].
Whereas endoscopic removal of small polyps is a straightforward routine
procedure, the resection of large lateral spreading lesions (LSL) and sessile
polyps require advanced techniques. Historically, these difficult lesions were
treated with surgery [5]. Nowadays the standard treatment is endoscopically
with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection
(ESD) [6, 7]. Colonic EMR is an effective and save minimally invasive
outpatient therapy for large sessile polyps, the greatest drawback is the high
adenoma recurrence rate of approximately 20% with even greater rates in
piecemeal resections [8, 9].


Although these recurrences are small and often easily treated endoscopically,
they require an intensive surveillance program. Interventions studied to
decrease EMR recurrences are argon plasma coagulation (APC) [10-13], thermal
ablation EMR [10, 14, 15] and extended EMR (X-EMR) [16]. Whilst the APC studies
are relatively small in size and findings being conflicting, a prospective
multicenter randomized trial in Australia with 390 patients by Klein et al.
[14] on thermal ablation, showed promising results. They conducted a study in
which patients were randomly assigned to thermal ablation of the entire
post-EMR mucosal defect margin or no additional intervention. Thermal ablation
was achieved using snare tip soft coagulation (STSC) originally used for
control of intraprocedural bleeding during polypectomy [17]. Their study
concluded that STSC is a fast, safe and effective method in significantly
decreasing the recurrence rate in EMR compared to a conservative approach,
respectively: 5.2 % versus 21.0 % (p<0.001). These results were corroborated
by a retrospective single center case-control study in 2019 (12% vs. 30%,
p=0.01) [15].


The results of the Australian group are promising, but performed only in
tertiary care centers. Furthermore, exclusion criteria of the RCT by Klein et
al. led to a 9.8% exclusion rate because of endoscopic incomplete resection.
Persistent polyp remnants can be removed with cold avulsion techniques or hot
biopsy forceps. The high incomplete resection percentage is perhaps due to
large polyps or to very conservative management of residual polyp removal
techniques. An alternative method to reduce recurrence after EMR, the so called
extended EMR method (X-EMR), failed to do so. In this technique, the resection
plan of the margins of the polyp were extended by at least 1cm. Interestingly,
X-EMR increased intraprocedural bleeding but did not significantly reduce the
recurrence rate (10.1% vs 11.7%) of colonic flat polyps [16]. So why is STSC
effective and X-EMR is not in reducing polyp recurrence after colonic EMR?
Perhaps the STSC technique is not as effective as promised by only 1 RCT? Or
did the X-EMR included polyps with center fibrosis? In the current proposal we
aim to generalize the intervention by including non-academic hospitals and
broaden the field of this intervention by including lesion with central
non-lifting parts, which can be removed by newer techniques (cold avulsion or
hot biopsy), which are nowadays common practice in our consortium. Lowering the
recurrence rate will potentially lead to fewer colonoscopies resulting in less
additional costs, less compliance burdens and less exposure to possible
procedure-related risks.

Does STSC decreases the recurrence rate after EMR in patients with large
lateral spreading or sessile polyps?

This study entails a patient-blinded multicenter prospective randomized
controlled trial conducted between October 2020 and October 2022 in 1 academic
and 4 non-academic hospitals in The Netherlands and Germany and it will take
place in the outpatient clinics of the participating centers.

After EMR, included patients will be randomly assigned in a 1:1 ratio to:

1. Intervention group - Soft tip snare coagulation (STSC) immediately after EMR

OR

2. Control group - No intervention after EMR

Patients will be randomly allocated by web-based randomization.

We anticipate to start our trial in the summer of 2020 with an inclusion period
of 1,5 year. The end of the study is defined the date of the last surveillance
colonoscopy ate six months after the final inclusion.

The technique that will be assessed is called soft tip snare coagulation
(STSC). It requires the same equipment used with standard EMR or snare
polypectomy: polypectomy snare. In this technique, the snare tip is not
complete extended from the sheath but the tip is positioned 1 to 2 mm beyond
the end of the snare sheath. The snare tip is applied directly on the tissue
compromising the entire border of the resection site creating a 2-3 mm
coagulation rim after energy transfer. The energy is delivered by a
microprocessor-controlled generator in accordance with standard polypectomy but
a reduced voltage. The usage of polyp snare type and microprocessor-controlled
generator depends on local expertise and availability.

Since these medical devices are already registered and widely used for
coagulation, additional safety studies are not required.
As mentioned before, Bahin et al. described the STSC technique in 2013 for
control of intraprocedural bleeding during EMR [1]. In this study, STSC was
able to reduce intraprocedural bleeding without adverse advents and without a
higher complication risk. Klein et al. and Kandel et al. adopted this technique
for thermal ablation in accordance with our study protocol. They also
demonstrated STSC to be a safe procedure with no adverse effect and without
higher procedural complication risks compared to the standard procedure [2,
3].
To our knowledge, there are no potential risks described. The aim of our study
is to compare the ability of STSC to reduce the recurrence rate after EMR. If
the recurrence rate is reduced with STSC, surveillance protocols can be more
flexible resulting in fewer colonoscopies with extended intervals.

We would like to emphasize that this intervention entails snares originally
designed for polypectomies. With STSC, instead of the entire snare, only the
tip is used for coagulation of mucosal tissue. This intervention is already
common among andvances endoscopists for the treatment of recurrent polyps,
visible residues and intraprocedural bleeding.



1. Fahrtash-Bahin, F., et al., Snare tip soft coagulation achieves effective
and safe endoscopic hemostasis during wide-field endoscopic resection of large
colonic lesions (with videos). Gastrointest Endosc, 2013. 78(1): p. 158-163 e1.
2. Klein, A., et al., Thermal Ablation of Mucosal Defect Margins Reduces
Adenoma Recurrence After Colonic Endoscopic Mucosal Resection.
Gastroenterology, 2019. 156(3): p. 604-613.e3.
3. Kandel, P., et al., Prophylactic Snare Tip Soft Coagulation and Its Impact
on Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Dig Dis Sci,
2019. 64(11): p. 3300-3306.

N.A.