Deep Submucosal Invasion a Poor Predictor of Lymph Node Metastasis in Colorectal Cancer

A systematic review and meta-analysis did not find deep submucosal invasion (DSI) as an independent predictor for lymph node metastasis (LNM) in the setting of colorectal cancer (CRC). These findings were published in Gastroenterology.

Publication databases were searched through July of 2021 for studies of LNM and histological risk factors among patients with T1 CRC who underwent endoscopic resection, radical surgery, or completion surgery. For the prediction of risk, only studies defining DSI as submucosal invasion 2-3 and/or ³1000 mm were included.

A total of 67 studies comprising 21,238 patients were included in this analysis. Patients had colon cancer (39.8%), rectal cancer (20.0%), or unknown CRC (40.2%). Lesions were described as nonpedunculated (43.4%) or had unclear descriptions (46.9%).

The rate of LNM was 11.2% (n=2363). In the overall univariate analysis, DSI was significantly associated with LNM (odds ratio [OR], 2.58; 95% CI, 2.10-3.18).Stratified by study approach, DSI was associated with LNM in studies using a 1000 mm cutoff (OR, 2.32; 95% CI, 1.80-2.97) and in studies on nonpedunculated lesions (OR, 2.86; 95% CI, 1.87-4.38).

In the multivariate analysis, however, DSI was not a significant predictor for LNM when other risk factors were taken into consideration (OR, 1.73; 95% CI, 0.96-3.12). LNM was associated with poor differentiation (OR, 2.14; 95% CI, 1.39-3.28), high-grade tumor budding (OR, 2.83; 95% CI, 2.06-3.88), and lymphatic and/or vascular invasion (OR, 3.16; 95% CI, 1.88-5.33).

These findings were consistent among studies of nonpedunculated lesions (OR, 1.32; 95% CI, 0.70-2.46), studies of lesions treated with primary radical surgery (OR, 1.26; 95% CI, 0.66-2.41), and in studies conducted in Asian countries (OR, 1.92; 95% CI, 0.91-4.05), the investigators noted.

The major limitation of this analysis was that most studies did not provide an accurate definition of LNM and histopathological techniques varied.

In this meta-analysis, DSI was not a strong predictor for LNM among patients with CRC when other risk factors were accounted for. These findings suggested to the researchers that additional risk factors in addition to DSI should be considered to guide decision making.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


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