Argon Plasma Coagulation Versus Endoscopic Mucosal Resection for Gastric Adenoma (CLER-GA)

Gastric adenomas with low-grade dysplasia (LGD) represent precancerous changes in the stomach lining. Unlike high-grade dysplasia (HGD), which carries a well-established high risk of progression to gastric cancer and is uniformly recommended for endoscopic resection, LGD has a much lower risk of malignant transformation. Some long-term follow-up studies suggest that fewer than 10% of LGD lesions progress to cancer within five years. As a result, there has been longstanding debate over whether LGD lesions, particularly those measuring 1 cm or smaller, should be actively treated or only monitored.

International guidelines differ on this issue. The Vienna classification recommends either endoscopic resection or close surveillance. The American Society of Gastrointestinal Endoscopy (ASGE) guidelines do not provide explicit recommendations for LGD, focusing instead on HGD and cancer. The British Society of Gastroenterology (BSG) advises complete removal of adenomas but without specifying the method. Only the updated European Society of Gastrointestinal Endoscopy (ESGE) guideline explicitly recommends endoscopic mucosal resection (EMR) for lesions smaller than 1 cm, while larger or suspicious lesions should be treated with endoscopic submucosal dissection (ESD). In contrast, Japanese and Korean gastric cancer guidelines primarily address early gastric cancer and provide no guidance specific to adenomas.

Currently, EMR and ESD are considered standard resection techniques. EMR is suitable for small, superficial lesions and allows en bloc removal with pathological confirmation, but it involves technical demands, longer procedure time, higher risk of complications, and greater costs. ESD extends these advantages to larger or fibrotic lesions but is even more technically demanding. In comparison, argon plasma coagulation (APC) is a non-contact ablative method using ionized argon gas to deliver high-frequency current. APC has been widely applied in therapeutic endoscopy for hemostasis and tissue ablation. It is technically simple, quicker, less invasive, and associated with fewer complications and lower costs. However, APC does not yield a resection specimen, making it impossible to confirm complete removal histologically, and the possibility of local recurrence remains.

Several retrospective studies have evaluated APC for gastric LGD, reporting local recurrence rates ranging from 1.7% to over 20%. The largest cohort suggested a recurrence rate of 2.6% for lesions ≤1 cm, compared to higher recurrence for 1-2 cm lesions. These results suggest that APC may be suitable for selected small LGD lesions, but the lack of randomized controlled trials (RCTs) leaves considerable uncertainty. Importantly, no RCT has directly compared APC with EMR, the standard resection method, in this specific population.

This study is therefore designed as a multicenter, randomized, single-blinded, controlled trial to evaluate whether APC is non-inferior to EMR in preventing local recurrence of gastric adenomas with LGD measuring 1 cm or smaller. A total of 160 adult participants will be enrolled across multiple academic hospitals in Korea. Eligible patients will be randomized 1:1 to receive either APC or EMR. Standard post-procedure management will be provided to all patients, including fasting, acid suppression, and routine monitoring. Participants will be followed for at least 12 months, with surveillance endoscopies scheduled at 3 months and 12 months to assess the treated site and obtain biopsies when indicated.

The primary endpoint is local recurrence rate at 12 months, defined as histological confirmation of LGD at the treated site. Secondary endpoints include overall procedure outcomes (complete ablation or en bloc resection), procedure-related complications (bleeding, perforation), procedure time, and hospitalization outcomes. Statistical analysis will follow both intention-to-treat and per-protocol principles, with non-inferiority margins prespecified.

Both APC and EMR are already established in routine practice and are not investigational devices in the United States. This trial does not involve an FDA IND or IDE. The significance of this study lies in generating high-quality prospective evidence that can directly inform clinical decision-making for patients with gastric LGD. If APC proves to be non-inferior to EMR, it could provide a simpler, less invasive, and more cost-effective alternative for selected patients with small adenomas, reducing procedure time and complication risk while maintaining effectiveness in preventing recurrence. Conversely, if APC shows inferior outcomes, it would reinforce EMR as the standard of care.

This study addresses an important knowledge gap in the management of gastric LGD and has potential to influence future guideline recommendations worldwide.