Systematic review and meta‐analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer

Abstract

Aim Lymph node (LN) metastases are present in up to 17% of early colorectal cancers (pT1). Identification of associated histopathological factors would enable counselling of patients regarding this risk.Method Pubmed and Embase were employed utilizing the terms 'early colorectal cancer', 'lymph node metastasis', 'submucosal invasion', 'lymphovascular invasion', 'tumour budding' and 'histological differentiation'. Analysis was performed using REVIEW MANAGER 5.1.Results Twenty-three cohort studies including 4510 patients were analysed. There was a significantly higher risk of LN metastasis with a depth of submucosal invasion > 1 mm than with lesser degrees of penetration (OR 3.87, 95% CI 1.50-10.00, P = 0.005). Lymphovascular invasion was significantly associated with LN metastasis (OR 4.81, 95% CI 3.14-7.37, P < 0.00001). Poorly differentiated tumours had a higher risk of LN metastasis compared with well or moderately differentiated tumours (OR 5.60, 95% CI 2.90-10.82, P < 0.00001). Tumour budding was found to be significantly associated with LN metastasis (OR 7.74, 95% CI 4.47-13.39, P < 0.001).Conclusion Meta-analysis of the current literature demonstrates that in early colorectal cancer a depth of submucosal invasion by the primary tumour of > 1 mm, lymphovascular invasion, poor differentiation and tumour budding are significantly associated with LN metastasis.

Patient gender as a factor associated with lymph node metastasis in T1 colorectal cancer: A systematic review and meta-analysis

“…Other studies also reported higher rates of LNM in female compared with male patients, although these differences were not statistically significant (11,12). Several systematic reviews and meta-analyses have investigated risk factors for LNM; however, none has focused on patient gender as a predictive factor for LNM to date (13)(14)(15)(16)(17). The aim of the present systematic review and meta-analysis was to assess whether the gender of patients with T1 colorectal cancer is predictive of LNM.…”

“…As LNM is difficult to assess preoperatively, the decision to perform radical surgery following endoscopic resection is based on the results of clinicopathological analysis. Several previous systematic reviews of small, retrospective studies have identified reliable pathological factors associated with the risk of LNM in T1 colorectal cancer (13)(14)(15)(16)(17). These meta-analyses reported that depth of submucosal invasion >1,000 µm, lymphovascular invasion, poorly differentiated tumors and tumor budding were all risk factors for LNM.…”

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study

“…Although the implication of budding/sprouting in deeply invasive colorectal cancer was first reported in 1989, 25 many studies have also focused on budding/sprouting as a risk factor of lymph node metastasis in T1 colorectal cancer. [12][13][14][15][26][27][28][29][30][31][32] Some investigators refer to findings similar to budding/sprouting as 'unfavorable histology at the invasive front,' 33 'focal dedifferentiation,' 34 or 'tumor cell dissociation,' 35 although the definition is not always consistent. 13,25,32,36 In the evaluation of budding/sprouting, we adopted the definition of Ueno et al 13 because it is widely used and has good reproducibility.…”

Risk Assessment in Early Colorectal Cancer: Histological and Molecular Markers

“…2). There is a significantly higher risk of nodal metastasis for sm3 (12-25%) compared with sm1 and 2 lesions (0-8%) [8,11,12], which has been confirmed in two recent meta-analyses [13,14]. Therefore, sm1 and 2 lesions lacking other unfavorable histological features may be treated by local excision alone [5].…”

“…For these specimens direct measurement of the absolute thickness of the invasive tumor from the muscularis mucosae to the leading edge of invasion may be an alternative. Different thresholds have been introduced, and meta-analyses proved a submucosa invasion depth of >1 mm and >2 mm to be significantly related to an increased risk of lymph node metastasis [13,14]. Although the system of assessing invasion by direct measurement appears simple, this method relies on the true identification of the level of the muscularis mucosae (which may be destroyed by the invasive tumor) and on the quality of pathological evaluation, as only sections cut perpendicular to the surface allow accurate measurement.…”