Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors

Abstract

Granular mixed laterally spreading tumors (GM-LSTs) have an intermediate level of risk for submucosal invasive cancer (SMICs) without clear signs of invasion (covert); the optimal resection method is uncertain. We aimed to determine the risk of covert SMIC in GM-LSTs based on clinical and endoscopic factors. METHODS:We collected data from 693 patients (50.6% male; median age, 69 years) with colorectal GM-LSTs, without signs of invasion, who underwent endoscopic resection (74.2%) or endoscopic submucosal dissection (25.2%) at 7 centers in Italy from 2016 through 2019. We performed multivariate and univariate analyses to identify demographic and endoscopic factors associated with risk of SMIC. We developed a multivariate model to calculate the number needed to treat (NNT) to detect 1 SMIC. RESULTS:Based on pathology analysis, 66 patients (9.5%) had covert SMIC. In multivariate analyses, increased risk of covert SMIC were independently associated with increasing lesion size (odds ratio per mm increase, 1.02, 95% CI, 1.01-1.03; P [ .003) and rectal location (odds ratio, 3.08; 95% CI, 1.62-5.83; P [ .004). A logistic regression model based on lesion size (with a cutoff of 40 mm) and rectal location identified patients with covert SMIC with 47.0% sensitivity, 82.6% specificity, and an area under the curve of 0.69. The NNT to identify 1 patient with a nonrectal SMIC smaller than 4 cm was 20; the NNT to identify 1 patient with a rectal SMIC of 4 cm or more was 5. CONCLUSIONS:In an analysis of data from 693 patients, we found the risk of covert SMIC in patients with GM-LSTs to be approximately 10%. GM-LSTs of 4 cm or more and a rectal location are high risk and should be treated by en-bloc resection. ClinicalTrials.gov, Number: NCT03836131.

Narrowing the Set of Target Lesions for Colorectal Endoscopic Submucosal Dissection

“…Because ESD is realistically the only endoscopic approach that can achieve en bloc resection of lesions this size, "en bloc resection" here is a surrogate for ESD. As noted, the relative ease and safety of ESD in the rectum and the high morbidity of surgical procedures on the rectum, merges nicely with this finding of high risk of SMIC in rectal GM-LSTs 4 cm in Rectal GM-LST 40 mm in size (such as this lesion) were found to have a 22% risk of submucosal invasive cancer in the study by D'Amico et al, 12 and thus were recommended to undergo en bloc resection. This lesion had deep submucosal invasion of adenocarcinoma within the nodule.…”

“…(B) A 45-mm rectal GM-LST. The arrows delineate the nodule.Rectal GM-LST 40 mm in size (such as this lesion) were found to have a 22% risk of submucosal invasive cancer in the study by D'Amico et al,12 and thus were recommended to undergo en bloc resection. This lesion had deep submucosal invasion of adenocarcinoma within the nodule.…”

“…In this issue of Clinical Gastroenterology and Hepatology, D'Amico et al 12 report a study focused on the risk of SMIC in the GM-LST subgroup of G-LSTs. This was a prospective, large (693 lesions), multicenter study from Italy.…”

“…Some additional data would be useful to fully interpret the study. First, the authors report 70% of all SMIC was "high risk," defined by D'Amico et al 12 as having lymphovascular invasion or positive lateral or deep margins. However, it is not clear how many of the large rectal lesions with SMIC that were resected en bloc had deep SMIC or other unfavorable histologic features, and therefore surgical resection was advisable despite en bloc endoscopic resection.…”

Issue Highlights

“…D'Amico and colleagues 6 The results of this prospective study suggest that the risk of SMIC in GM-LSTs greater or equal to 40 mm in the rectum approximates that of non-granular LSTs, while non-rectal GM-LSTS less than 40 mm present only slightly higher risk of SMIC than homogenous granular LSTs. Further studies can help establish the prevalence of SMIC in all LST types and serve to inform the best endoscopic or surgical approach for these patients.…”