Meta-analysis of Histopathological Features of Primary Colorectal Cancers that Predict Lymph Node Metastases

Treatment decisions for colorectal cancer vary based on lymph node status. While some histopathological features of the primary tumor correlate with lymph node spread, the relative influences of these risk factors are not well quantified. This study aims to systematically review published studies relating histopathological features of primary colorectal cancer to the presence of lymph node metastases and to determine how reliable certain factors might be at predicting nodal metastasis when only the primary lesion is available for study. Inclusive literature search using EMBASE and Ovid MEDLINE databases plus manual reference checks of all articles correlating lymphatic spread with colorectal cancer (any T stage) from 1984 to mid-2008 was performed. This search generated two levels of screening utilized on 602 citations, yielding 123 articles for full review. Data reported from 76 articles were chosen. The relative influence of each histopathological feature on the likelihood of lymphatic metastases was determined. Fixed-effects meta-analysis was performed, and results were reported as Mantel-Haenszel odds ratios (OR). Of 42 histopathological features analyzed, only 40.4% were reported in > 2 articles. The positive predictive values for the top quartile of most frequently reported risk factors were 25.5-86.4%. Among the commonly reported histopathological findings, lymphatic invasion (OR, 8.62) significantly outperformed tumor depth (T2 vs. T1; OR, 2.62) and overall differentiation (OR, 2.38) in predicting nodal spread. For the rectal cancer subset, risk factors differed from the overall colorectal group in predictive ability; poor differentiation at the invasive front (OR, 6.08) and tumor budding (OR, 5.82) were the most predictive. This literature search is limited by the small number of studies examining only rectal cancers and the potential changes in histological and/or surgical techniques over the study period. No single histopathological feature of colorectal cancer reliably predicted lymph node metastases. Several risk factors that correlate highly with nodal disease are not routine components of standard pathology reports. Until further research establishes histopathological or molecular patterns for predicting lymph node spread, caution should be exercised when basing treatment decisions solely on these factors.