Tumor Budding as a Risk Factor for Nodal Metastasis in Pt1 Colorectal Cancers: A Meta-Analysis

Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of sub-mucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the post-surgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than five cancer cells at the tumor invasive front, among the variables that must be included in histological reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report due to the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1-CRCs, this meta-analysis evaluated 41 studies involving a total of 10,137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1-CRC. In comparing TB-positive (684/2,401; 28.5%) versus TB-negative (557/7,736; 7.2%) patients, the prevalence of nodal disease resulted in an OR value of 6.44 (95%CI: 5.26-7.87; p<0.0001; I2=30%). This increased risk of regional nodal metastasis was further confirmed after accounting for potential confounders. These results support the priority of histologically reporting TB in any endoscopically removed pT1-CRC to direct more appropriate patient management.