Deep submucosal invasion does not have significant predictive value for lymph node metastasis in patients with T1 colorectal cancer relative to other histological criteria such as tumor budding, lymphovascular invasion and poor differentiation, suggests a new study published in the journal Gastroenterology.¹

Zwater et al conducted a meta-analysis of 67 studies, involving 21,238 patients, to determine the risk for lymph node metastasis with deep submucosal invasion in patients with T1 colorectal cancer (CRC). Studies were included for review in the meta-analysis if risk factors (such as poor differentiation, deep submucosal invasion, lymphovascular invasion) and/or high-grade tumor budding were also included in multivariable analysis or the LNM-rate of DSI was described in the absence of tumor budding, poor differentiation and lymphovascular invasion.

The overall rate of lymph node metastasis was 11.2%, which was much higher in CRCs with deep submucosal invasion with odds ratio of 2.58.

On multivariate meta-analysis, DSI was not a  significant predictor for lymph node metastasis (OR 1.73) in eight trials involving 3621 patients. However, a significant association was observed between lymph node metastasis and poor differentiation (OR 2.14), tumor budding (OR 2.83) and lymphovascular invasion (OR 3.16). Another series of eight studies of 1146 patients examined deep submucosal invasion as a sole risk factor in the absence of tumor budding, lymphovascular invasion and poor differentiation. The absolute risk of lymph node metastasis was low (2.6%) in this series and the pooled incidence rate was 2.83.

The presence of deep submucosal invasion is traditionally considered as a high-risk factor for lymph node metastasis and strongly influences the decision to proceed with radical surgery in CRC patients.

This meta-analysis has, for the first time, not shown any independent association between deep submucosal invasion and lymph node metastasis and calls for revisiting the role of DSI as the sole criterion for selection of treatment. Based on their findings, the authors write, “In light of the expanding spectrum of local resection methods and increasing interest in organ-preservation, a management shift towards a local excision as initial approach for amenable DSI cases to guide shared decision-making is expected.” Given the low risk for lymph node metastasis, they also suggest active surveillance may be “a reasonable approach” in place of surgery in appropriate patients.

Reference

1. Zwager LW, et al. Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: a meta-analysis. Gastroenterology. 2022 Apr 15;S0016-5085(22)00366-3. doi: 10.1053/j.gastro.2022.04.010.