Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: a meta-analysis

Background & aims: Deep submucosal invasion (DSI) is considered a key risk factor for lymph node metastasis (LNM) and important criterion to recommend surgery in T1 colorectal cancer (CRC). However, metastatic risk for DSI is shown to be low in absence of other histological risk factors. This meta-analysis determines the independent risk of DSI for LNM. Methods: Suitable studies were included to establish LNM-risk for DSI in univariable analysis. To assess DSI as independent risk factor, studies were eligible if 1) risk factors (DSI, poor differentiation (PD), lymphovascular invasion (LVI) and/or high-grade tumor budding (TB)) were simultaneously included in multivariable analysis or 2) LNM-rate of DSI was described in absence of PD, LVI and TB. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results: Sixty-seven studies (21,238 patients) were included. Overall LNM-rate was 11.2% and significantly higher for DSI-positive cancers (OR 2.58;95%CI2.10-3.18). Eight studies (3621 patients) were included in multivariable meta-analysis and did not weigh DSI a significant predictor for LNM (OR 1.73;95%CI0.96-3.12). As opposed to a significant association between LNM and PD (OR 2.14;95%CI 1.39-3.28), TB (OR 2.83;95%CI2.06-3.88) and LVI (OR 3.16;95%CI1.88-5.33). Eight studies (1146 patients) analyzed DSI as solitary risk factor: absolute risk of LNM was 2.6% and pooled incidence rate 2.83 (95%CI1.66-4.78). Conclusions: DSI is not a strong independent predictor for LNM and should be reconsidered as a sole indicator for oncologic surgery. The expanding armamentarium for local excision as first-line treatment prompts serious consideration in amenable cases to tailor T1 CRC management.