CEA-targeted fluorescence endoscopy for the detection of high-grade dysplasia and early invasive rectal cancer: A proof-of-concept trial.

Abstract

Accurate recognition of high-grade dysplasia (HGD) and early invasive carcinoma (IC) within colorectal polyps is essential for selecting the preferred local resection technique. However, optical endoscopic diagnosis can be challenging, particularly in large and advanced polyps. This study investigates whether carcinoembryonic antigen (CEA)-targeted near-infrared fluorescence (NIRF) imaging can distinguish polyps containing HGD/IC from polyps solely containing low-grade dysplasia (LGD), given prior evidence of CEA overexpression in HGD/IC relative to LGD. Patients scheduled for local en-bloc endoscopic resection of advanced rectal polyps were included in the study and received 5 mg or 10 mg intravenous SGM-101, a CEA-targeted fluorescent agent. In vivo imaging was performed using a rigid Quest-Olympus NIRF-endoscope, followed by ex vivo whole-specimen and bread-loaf imaging using the PEARL imaging system. The primary endpoint was the NIRF tumour-to-low-grade-dysplasia ratio (TDR; HGD/IC divided by LGD) performed on bread loafs, as this method enabled direct pathological correlation. Secondary endpoints included dose-finding as well as sensitivity and specificity for detecting HGD/IC. A total of 22 patients were included, with 9/22 containing LGD only and 13/22 containing HGD/IC. Eleven patients received 10 mg and 11 received 5 mg SGM-101. Ex vivo bread-loaf imaging showed a median (IQR) TDR of 1.7 (1.3-2.9), with higher values in the 10 mg group of 2.5 (2.0-3.5) compared to the 1.3 (1.2-1.6) in the 5 mg group (p = 0.023). The sensitivity for detecting HGD/IC was 86% (2 false-negatives), and specificity was 88% (1 false-positive). Although with limited sample size, this study demonstrates proof-of-concept of CEA-targeted NIRF-imaging in differentiating HGD/IC bearing polyps from completely benign LGD polyps. Clinical utility, including its impact on treatment decision-making and patient outcomes, remains to be demonstrated in future, larger prospective studies. NCT06280690.